БОЛЕЗНЬ ФАБРИ

Болезнь Фабри (БФ) представляет собой прогрессирующее наследственное, сцепленное с Х-хромосомой нарушение метаболизма гликосфинголипидов, обусловленное снижением или полным отсутствием активности лизосомальной α-галактозидазы А. БФ встречается у представителей всех без исключения этнических групп, но опубликованные данные о встречаемости БФ – 1 на 100000 могут тыть, вероятно, ниже истинной распространённости данного заболевания. При классическом варианте болезни у гемизиготных мужчин с отсутствием остаточной активности α-галактозидазы А могут иметься все характерные симптомы – неврологические (боль), кожные (ангиокератома), почечные (протеинурия, почечная недостаточность), сердечно-сосудистые (кардиомиопатия, аритмия), а также кохлеовестибулярные и цереброваскулярные (транзиторные ишемические атаки, инсульты), тогда как у гетерозиготных женщин симптомы обыкновенно варьируют от очень мягких до тяжелых. Считается, что недостаточность активности лизосомальной α-галактозидазы А приводит к прогрессивному накоплению в лизосомах глоботриозилцерамида, что и запускает каскад клеточных процессов. Обнаружение значимой недостаточности α-галактозидазы является определяющим при постановке диагноза у гемизиготных мужчин. Иногда ферментный анализ помогает в обнаружении гетерозигот, однако нередко не позволяет сделать окончательный вывод из-за случайной инактивации Х- хромосомы, в связи с чем проведение молекулярных исследований (генотипирование) у женщин является обязательным. У пациентов детского возраста необходимо исключение других возможных причин болевого синдрома, таких как ревматоидный артрит и невралгические боли. У взрослых в ряде случаев требуется проведение дифференциальной диагностики с рассеянным склерозом. Пренатальная диагностика, осуществляемая путём установления активности ферментов или исследования ДНК в ворсинах хориона или культивированных амниотических клетках, по этическим причинам проводится только у плодов мужского пола. Возможна также преимплантационная диагностика. Однако существование атипичных вариантов и широкая доступность специфической терапии существенно затрудняют генетическое консультирование. Не так давно был предложен специфический метод лечения – заместительная энзимная терапия, заключающаяся в использовании рекомбинантной человеческой α-галактозидазы А, но анализ её отдалённых результатов пока не завершен. Традиционное лечение включает использование анальгетиков для облегчения болевого синдрома, нефропротективной (ингибиторы ангиотензин превращающего фермента и блокаторы АТ1-рецепторов) и антиаритмической терапии, а для пациентов с терминальной почечной недостаточностью – диализа и трансплантации почки. С возрастом прогрессирует повреждение жизненно важных органов и систем, с развитием, на определенном этапе, их функциональной недостаточности. Терминальная почечная недостаточность, угрожающие жизни сердечно-сосудистые или цереброваскулярные осложнения сокращают продолжительность жизни мужчин и женщин, не получающих терапию, в сравнении с общей популяцией на 20 и 10 лет соответственно. Наряду с тем, что существуют веские доказательства того, что длительная энзимная терапия может замедлять прогрессирование заболевания, необходимо подчеркнуть важность применения дополнительных методов лечения и возможности разработки пероральной терапии, что стимулирует исследования в области действующих на активные участки, шаперонов. 

Признательности. Я особенно благодарен моим пациентам и их семьям. Я благодарю своего сотрудника Dr. Karelle BENISTAN, MD. Я благодарю Genzyme Corporation и Shire HGT за их постоянную научную поддержку. Эта работа была поддержана Министерством Здоровья Франции в рамках программы «Plan National Maladies Rares».

Конфликт интересов. Доминик П. Гермэйн является консультантом Genzyme Corporation и Shire HGT. Он получил оплату выступлений, поддержку исследований и гонорар от Genzyme Corporation и Shire HGT.

1. Anderson W. A case of «Angeio-keratoma». Br J Dermatol 1898; 10:113-117

2. Fabry J. Ein Beitrag zur Kenntnis der Purpura haemorragica nodularis (Purpura papulosa hemorrhagica Hebrae). Arch Dermatol Syphilol 1898; 43:187-200

3. Sweeley CC, Klionsky B. Fabry’s disease: classification as a sphingolipidosis and partial characterization of a novel glycolipid. J Biol Chem 1963; 238:3148-3150

4. Brady RO, Gal AE, Bradley RM, et al. Enzymatic defect in Fabry’s disease: ceramide-trihexosidase deficiency. N Engl J Med 1967; 276:1163-1167

5. Kint JA. The enzyme defect in Fabry’s disease. Nature 1970; 227:1173

6. De Duve C. Exploring cells with a centrifuge. Science 1975; 189:186-194

7. Desnick RJ, Ioannou YA, Eng CM. Alpha-galactosidase A deficiency: Fabry disease. In The metabolic and molecular bases of inherited disease. Edited by Scriver CR, Beaudet AL, Sly WS, Valle D, Childs B, Kinzler KW, Vogelstein B. New York, McGraw Hill; 2001; 3733-3774

8. Popli S, Leehey DJ, Molnar ZV, et al. Demonstration of Fabry’s disease deposits in placenta. Am J Obstet Gynecol 1990; 162: 464-465

9. Vedder AC, Strijland A, vd Bergh Weerman MA, et al. Manifestations of Fabry disease in placental tissue. J Inherit Metab Dis 2006; 29: 106-111

10. Hers HG. Inborn Lysosomal Diseases. Gastroenterology 1965; 48:625-633

11. Neufeld EF. Lysosomal storage diseases. Annu Rev Biochem 1991; 60:257-280

12. Lucke T, Hoppner W, Schmidt E, et al. Fabry disease: reduced activities of respiratory chain enzymes with decreased levels of energy-rich phosphates in fibroblasts. Mol Genet Metab 2004; 82:93-97

13. Palecek T, Bultas J, Hajek M, et al. Association between cardiac energy metabolism and gain of left ventricular mass in Fabry disease. Int J Cardiol 2009; 144:337-339

14. Das AM, Naim HY. Biochemical basis of Fabry disease with emphasis on mitochondrial function and protein trafficking. Adv Clin Chem 2009; 49:57-71

15. Park JL, Shu L, Shayman JA. Differential involvement of COX1 and COX2 in the vasculopathy associated with the {alpha}- galactosidase A-knockout mouse. Am J Physiol Heart Circ Physiol 2009; 296:1133-1140

16. Park S, Kim JA, Joo KY, et al. Globotriaosylceramide leads to KCa3.1 channel dysfunction: A new insight into endothelial dysfunction in Fabry disease. Cardiovasc Res 2010; in press

17. Shen JS, Meng XL, Moore DF, et al. Globotriaosylceramide induces oxidative stress and up-regulates cell adhesion molecule expression in Fabry disease endothelial cells. Mol Genet Metab 2008; 95:163-168

18. Chevrier M, Brakch N, Lesueur C, et al. Autophagosome maturation is impaired in Fabry disease. Autophagy 2010; in press

19. Weidemann F, Breunig F, Beer M, et al. JM: The variation of morphological and functional cardiac manifestation in Fabry disease: potential implications for the time course of the disease. Eur Heart J 2005; 26:1221-1227

20. Beer M, Weidemann F, Breunig F, et al. Impact of enzyme replacement therapy on cardiac morphology and function and late enhancement in Fabry‘s cardiomyopathy. Am J Cardiol 2006; 97:1515-1518

21. Moon JC, Sheppard M, Reed E, et al. The histological basis of late gadolinium enhancement cardiovascular magnetic resonance in a patient with Anderson-Fabry disease. J Cardiovasc Magn Reson 2006; 8:479-482

22. Torra R. Renal manifestations in Fabry disease and therapeutic options. Kidney Int Suppl 2008; S29-32

23. Hopkin RJ, Bissler J, Banikazemi M, et al. Characterization of Fabry Disease in 352 Pediatric Patients in the Fabry Registry. Pediatr Res 2008; 64:550-555

24. Wilcox WR, Oliveira JP, Hopkin RJ, et al. Females with Fabry disease frequently have major organ involvement: lessons from the Fabry Registry. Mol Genet Metab 2008; 93:112-128

25. Schiffmann R, Warnock DG, Banikazemi M, et al. Fabry disease: progression of nephropathy, and prevalence of cardiac and cerebrovascular events before enzyme replacement therapy. Nephrol Dial Transplant 2009; 24:2102-2111

26. MacDermot KD, Holmes A, Miners AH. Anderson-Fabry disease: clinical manifestations and impact of disease in a cohort of 60 obligate carrier females. J Med Genet 2001; 38:769-775

27. Mehta A, Beck M, Eyskens F, et al. Fabry disease: a review of current management strategies. QJM 2010; 103:641-659

28. Elleder M, Bradova V, Smid F, et al. Cardiocyte storage and hypertrophy as a sole manifestation of Fabry’s disease. Virchows Arch Pathol Anat Histopathol 1990; 417:449-455

29. Nakao S, Takenaka T, Maeda M, et al. An atypical variant of Fabry’s disease in men with left ventricular hypertrophy. N Engl J Med 1995; 333:288-293

30. Nakao S, Kodama C, Takenaka T, Tanaka A, Yasumoto Y, Yoshida A, Kanzaki T, Enriquez AL, Eng CM, Tanaka H, Tei C, Desnick RJ: et al. Fabry disease: detection of undiagnosed hemodialysis patients and identification of a «renal variant» phenotype. Kidney Int 2003; 64:801-807

31. Maier EM, Osterrieder S, Whybra C et al. Disease manifestations and × inactivation in heterozygous females with Fabry disease. Acta Paediatr Suppl 2006; 95:30-38

32. Migeon BR. X inactivation, female mosaicism, and sex differences in renal diseases. J Am Soc Nephrol 2008; 19:2052-2059

33. Poorthuis BJ, Wevers RA, Kleijer WJ, et al. The frequency of lysosomal storage diseases in The Netherlands. Hum Genet 1999; 105:151-156

34. Meikle PJ, Hopwood JJ, Clague AE, Carrey WF. Prevalence of lysosomal storage disorders. JAMA 1999; 281:249-254

35. Spada M, Pagliardini S, Yasuda M, et al. High incidence of later-onset fabry disease revealed by newborn screening. Am J Hum Genet 2006; 79:31-40

36. Hwu WL, Chien YH, Lee NC, et al. Newborn screening for Fabry disease in Taiwan reveals a high incidence of the later-onset GLA mutation c.936+919G > A (IVS4+919G > A). Hum Mutat 2009; 30:1397-1405

37. Lin HY, Chong KW, Hsu JH, et al. High Incidence of the cardiac variant of Fabry disease revealed by newborn screening in the Taiwan Chinese population. Circ Cardiovasc Genet 2009;, 2:450-456

38. Dutsch M, Marthol H, Stemper B, et al. Small fiber dysfunction predominates in Fabry neuropathy. J Clin Neurophysiol 2002; 19:575-586

39. Cable WJ, Kolodny EH, Adams RD. Fabry disease: impaired autonomic function. Neurology 1982; 32:498-502

40. Ramaswami U, Whybra C, Parini R, et al. Clinical manifestations of Fabry disease in children: data from the Fabry Outcome Survey. Acta Paediatr 2006; 95:86-92

41. Desnick RJ, Brady RO. Fabry disease in childhood. J Pediatr 2004; 144:S20-26.

42. Zarate YA, Hopkin RJ. Fabry’s disease. Lancet 2008; 372:1427-1435

43. Hoffmann B, Beck M, Sunder-Plassmann G, et al. Nature and prevalence of pain in Fabry disease and its response to enzyme replacement therapy--a retrospective analysis from the Fabry Outcome Survey. Clin J Pain 2007; 23:535-542

44. Charrow J. A 14-year-old boy with pain in hands and feet. Pediatr Ann 2009; 38:190-192

45. Hilz MJ, Stemper B, Kolodny EH. Lower limb cold exposure induces pain and prolonged small fiber dysfunction in Fabry patients. Pain 2000; 84:361-365

46. Miners AH, Holmes A, Sherr L, et al. Assessment of healthrelated quality-of-life in males with Anderson Fabry Disease before therapeutic intervention. Qual Life Res 2002; 11:127-133

47. Cole AL, Lee PJ, Hughes DA, et al. Depression in adults with Fabry disease: a common and under-diagnosed problem. J Inherit Metab Dis 2007; 30:943-951

48. Naleschinski D, Arning K, Baron R. Fabry disease - Pain doctors have to find the missing ones. Pain 2009; 145:10-11.

49. Sheth KJ, Werlin SL, Freeman ME, Hodach AE. Gastrointestinal structure and function in Fabry’s disease. Am J Gastroenterol 1981; 76:246-251

50. Hoffmann B, Schwarz M, Mehta A, Keshav S. Gastrointestinal symptoms in 342 patients with Fabry disease: prevalence and response to enzyme replacement therapy. Clin Gastroenterol Hepatol 2007; 5:1447-1453

51. Eng CM, Germain DP, Banikazemi M, et al. Fabry disease: guidelines for the evaluation and management of multi-organ system involvement. Genet Med 2006; 8:539-548

52. Kang WH, Chun SI, Lee S. Generalized anhidrosis associated with Fabry’s disease. J Am Acad Dermatol 1987; 17:883-887

53. Orteu CH, Jansen T, Lidove O, et al. Fabry disease and the skin: data from FOS, the Fabry Outcome Survey. Br J Dermatol 2007; 157:331-337

54. Gupta SN, Ries M, Murray GJ, et al. Skin-impedance in Fabry Disease: a prospective, controlled, non-randomized clinical study. BMC Neurol 2008; 8:41

55. Shelley ED, Shelley WB, Kurczynski TW. Painful fingers, heat intolerance, and telangiectases of the ear: easily ignored childhood signs of Fabry disease. Pediatr Dermatol 1995; 12:215-219

56. Germain DP. [Fabry’s disease (alpha-galactosidase-A deficiency): physiopathology, clinical signs, and genetic aspects]. J Soc Biol 2002; 196:161-173

57. Mohrenschlager M, Braun-Falco M, Ring J, Abeck D. Fabry disease: recognition and management of cutaneous manifestations. Am J Clin Dermatol 2003; 4:189-196

58. Wattanasirichaigoon D, Svasti J, Cairns JR, et al. Clinical and molecular characterization of an extended family with Fabry disease. J Med Assoc Thai 2006; 89:1528-1535

59. Keilmann A, Hajioff D, Ramaswami U. Ear symptoms in children with Fabry disease: data from the Fabry Outcome Survey. J Inherit Metab Dis 2009; 32:739-744

60. Ries M, Gupta S, Moore DF, et al. Pediatric Fabry disease. Pediatrics 2005; 115:e344-355

61. Kampmann C, Wiethoff CM, Whybra C, et al. Cardiac manifestations of Anderson-Fabry disease in children and adolescents. Acta Paediatr 2008; 97:463-469

62. Cabrera-Salazar MA, O‘Rourke E, Charria-Ortiz G, Barranger JA. Radiological evidence of early cerebral microvascular disease in young children with Fabry disease. J Pediatr 2005; 147:102-105

63. Gubler MC, Lenoir G, Grunfeld JP, et al. Early renal changes in hemizygous and heterozygous patients with Fabry’s disease. Kidney Int 1978; 13:223-235

64. Sessa A, Meroni M, Battini G, et al. Renal pathological changes in Fabry disease. J Inherit Metab Dis 2001; 24:66-70

65. Tondel C, Bostad L, Hirth A, Svarstad E. Renal biopsy findings in children and adolescents with Fabry disease and minimal albuminuria. Am J Kidney Dis 2008; 51:767-776

66. Ramaswami U, Najafian B, Schieppati A, et al. Assessment of renal pathology and dysfunction in children with Fabry disease. Clin J Am Soc Nephrol 2010; 5:365-370

67. Schwartz GJ, Haycock GB, Edelmann CM Jr, Spitzer A. A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics 1976; 58:259-263

68. Schwartz GJ, Munoz A, Schneider MF, et al. New equations to estimate GFR in children with CKD. J Am Soc Nephrol 2009; 20:629-637

69. Counahan R, Chantler C, Ghazali S, et al. Estimation of glomerular filtration rate from plasma creatinine concentration in children. Arch Dis Child 1976; 51:875-878

70. Tondel C, Ramaswami U, Aakre KM, et al. Monitoring renal function in children with Fabry disease: comparisons of measured and creatinine-based estimated glomerular filtration rate. Nephrol Dial Transplant 2010; 25:1507-1513

71. Fogo AB, Bostad L, Svarstad E, et al. Scoring system for renal pathology in Fabry disease: report of the international study group of fabry nephropathy (ISGFN). Nephrol Dial Transplant 2010; 25:2168-2177

72. Fervenza FC, Torra R, Lager DJ. Fabry disease: an underrecognized cause of proteinuria. Kidney Int 2008; 73:1193-1199

73. Ortiz A, Oliveira JP, Waldek S, et al. Nephropathy in males and females with Fabry disease: cross-sectional description of patients before treatment with enzyme replacement therapy. Nephrol Dial Transplant 2008; 23:1600-1607

74. Branton MH, Schiffmann R, Sabnis SG, et al. Natural history of Fabry renal disease: influence of alpha-galactosidase A activity and genetic mutations on clinical course. Medicine (Baltimore) 2002; 81:122-138

75. Froissart M, Benistan K, Germain DP. [Functional renal investigation in Fabry disease]. Presse Med 2007; 36:S36-42

76. Wanner C, Oliveira JP, Ortiz A, et al. Prognostic indicators of renal disease progression in adults with Fabry disease: Natural history data from the Fabry Registry. Clin J Am Soc Nephrol 2010; in press

77. Warnock DG, Valbuena C, West M, Oliveira JP. Renal manifestations of Fabry disease. In Fabry disease. Edited by Elstein D, Altarescu G, Beck M. Dordrecht, Heidelberg, Springer; London, New-York, 2010;211-244

78. Linhart A, Palecek T, Bultas J, et al. New insights in cardiac structural changes in patients with Fabry’s disease. Am Heart J 2000; 139:1101-1108

79. Kampmann C, Baehner F, Whybra C, et al. Cardiac manifestations of Anderson-Fabry disease in heterozygous females. J Am Coll Cardiol 2002; 40:1668-1674

80. Senechal M, Germain DP. Fabry disease: a functional and anatomical study of cardiac manifestations in 20 hemizygous male patients. Clin Genet 2003; 63:46-52

81. Shah JS, Hughes DA, Sachdev B, et al. Prevalence and clinical significance of cardiac arrhythmia in Anderson-Fabry disease. Am J Cardiol 2005; 96:842-846

82. Elliott PM, Kindler H, Shah JS, et al. Coronary microvascular dysfunction in male patients with Anderson-Fabry disease and the effect of treatment with alpha galactosidase A. Heart 2006; 92:357-360

83. Hasegawa H, Takano H, Shindo S, et al. Images in cardiovascular medicine. Transition from left ventricular hypertrophy to massive fibrosis in the cardiac variant of Fabry disease. Circulation 2006; 113:e720-721

84. Linhart A, Kampmann C, Zamorano JL, et al. Cardiac manifestations of Anderson-Fabry disease: results from the international Fabry outcome survey. Eur Heart J 2007; 28:1228-1235

85. Kampmann C, Linhart A, Baehner F, et al. Onset and progression of the Anderson-Fabry disease related cardiomyopathy. Int J Cardiol 2008; 130:367-373

86. Takenaka T, Teraguchi H, Yoshida A, et al. Terminal stage cardiac findings in patients with cardiac Fabry disease: an electrocardiographic, echocardiographic, and autopsy study. J Cardiol 2008; 51:50-59

87. Mehta A, Clarke JT, Giugliani R, et al. Natural course of Fabry disease: changing pattern of causes of death in FOS - Fabry Outcome Survey. J Med Genet 2009; 46:548-552

88. Linhart A, Elliott PM. The heart in Anderson-Fabry disease and other lysosomal storage disorders. Heart 2007; 93:528-535

89. Pieroni M, Chimenti C, Ricci R, et al. Early detection of Fabry cardiomyopathy by tissue Doppler imaging. Circulation 2003; 107:1978-1984

90. Pieroni M, Chimenti C, Russo A, et al. Tissue Doppler imaging in Fabry disease. Curr Opin Cardiol 2004, 19:452-457

91. Weidemann F, Breunig F, Beer M, et al. Improvement of cardiac function during enzyme replacement therapy in patients with Fabry disease: a prospective strain rate imaging study. Circulation 2003; 108:1299-1301

92. Palecek T, Dostalova G, Kuchynka P, et al. Right ventricular involvement in Fabry disease. J Am Soc Echocardiogr 2008; 21:1265-1268

93. Niemann M, Breunig F, Beer M, et al. The right ventricle in Fabry disease: natural history and impact of enzyme replacement therapy. Heart 2010; in press

94. Kampmann C, Baehner FA, Whybra C, et al. The right ventricle in Fabry disease. Acta Paediatr Suppl 2005; 94:15-18

95. Sheth KJ, Thomas JP Jr. Electrocardiograms in Fabry’s disease. J Electrocardiol 1982; 15:153-156

96. Yokoyama A, Yamazoe M, Shibata A. A case of heterozygous Fabry’s disease with a short PR interval and giant negative T waves. Br Heart J 1987; 57:296-299

97. Wise D. Short P-R intervals and tachyarrhythmias in Fabry’s disease. Postgrad Med J 1986; 62:969

98. Ikari Y, Kuwako K, Yamaguchi T. Fabry’s disease with complete atrioventricular block: histological evidence of involvement of the conduction system. British Heart J 1992; 68:323-325

99. Mehta J, Tuna N, Moller JH, Desnick RJ. Electrocardiographic and vectorcardiographic abnormalities in Fabry‘s disease. Am Heart J 1977; 93:699-705

100. Von Scheidt W, Eng CM, Fitzmaurice TF, et al. An atypical variant of Fabry‘s disease with manifestations confined to the myocardium. N Engl J Med 1991; 324:395-399

101. Goldman ME, Cantor R, Schwartz MF, et al. Echocardiographic abnormalities and disease severity in Fabry’s disease. J Am Coll Cardiol 1986; 7:1157-1161

102. Weidemann F, Strotmann JM, Niemann M, et al. Heart valve involvement in Fabry cardiomyopathy. Ultrasound Med Biol 2008; 35:730-735

103. Kalliokoski RJ, Kalliokoski KK, Sundell J, et al. Impaired myocardial perfusion reserve but preserved peripheral endothelial function in patients with Fabry disease. J Inherit Metab Dis 2005; 28:563-573

104. Bierer G, Kamangar N, Balfe D, et al. Cardiopulmonary exercise testing in Fabry disease. Respiration 2005; 72:504-511

105. Lobo T, Morgan J, Bjorksten A, et al. Cardiovascular testing in Fabry disease: exercise capacity reduction, chronotropic incompetence and improved anaerobic threshold after enzyme replacement. Intern Med J 2008; 38:407-414

106. Hilz MJ, Marthol H, Schwab S, et al. Enzyme replacement therapy improves cardiovascular responses to orthostatic challenge in Fabry patients. J Hypertens 2010; 28:1438-1448

107. Germain DP, Diebold B, Peyrard S, et al. Aortic root dilatation is highly prevalent in male patients affected with Fabry disease and correlates with the presence of a megadolicho-ectatic basilar artery [abstract]. Am J Hum Genet 2007; 81:300

108. Kahn P. Anderson-Fabry disease: a histopathological study of three cases with observations on the mechanism of production of pain. J Neurol Neurosurg Psychiatry 1973; 36:1053-1062

109. Maag R, Binder A, Maier C, et al. Detection of a characteristic painful neuropathy in Fabry disease: A pilot study. Pain Med 2008; 9:1217-1223

110. Fellgiebel A, Muller MJ, Ginsberg L. CNS manifestations of Fabry’s disease. Lancet Neurol 2006; 5:791-795

111. Sims K, Politei J, Banikazemi M, Lee P. Stroke in Fabry disease frequently occurs before diagnosis and in the absence of other clinical events: natural history data from the Fabry Registry. Stroke 2009; 40:788-794

112. Mitsias P, Levine SL. Cerebrovascular complications of Fabry’s disease. Ann Neurol 1996; 40:8-17

113. Clavelou P, Besson G, Elziere C, et al. [Neurological aspects of Fabry’s disease]. Rev Neurol (Paris) 2006; 162:569-580

114. Mendez MF, Stanley TM, Medel NM, et al. The vascular dementia of Fabry’s disease. Dement Geriatr Cogn Disord 1997; 8:252-257

115. Okeda R, Nisihara M. An autopsy case of Fabry disease with neuropathological investigation of the pathogenesis of associated dementia. Neuropathology 2008; 28:532-540

116. Fellgiebel A, Keller I, Marin D, et al. Diagnostic utility of different MRI and MR angiography measures in Fabry disease. Neurology 2009; 72:63-68

117. DeGraba T, Azhar S, Dignat-George F, et al. Profile of endothelial and leukocyte activation in Fabry patients. Ann Neurol 2000; 47:229-233

118. Moore DF, Scott LT, Gladwin MT, et al. Regional cerebral hyperperfusion and nitric oxide pathway dysregulation in Fabry disease: reversal by enzyme replacement therapy. Circulation 2001; 104:1506-1512

119. Moore DF, Altarescu G, Ling GS, et al. Elevated cerebral blood flow velocities in Fabry disease with reversal after enzyme replacement. Stroke 2002; 33:525-531

120. Schiffmann R. Fabry disease. Pharmacol Ther 2009, 122:65-77

121. Kaneski CR, Moore DF, Ries M, et al. Myeloperoxidase predicts risk of vasculopathic events in hemizgygous males with Fabry disease. Neurology 2006; 67:2045-2047

122. Hilz MJ, Kolodny EH, Brys M, et al. Reduced cerebral blood flow velocity and impaired cerebral autoregulation in patients with Fabry disease. J Neurol 2004; 251:564-570

123. Fellgiebel A, Albrecht J, Dellani PR, et al. Quantification of brain tissue alterations in Fabry disease using diffusion-tensor imaging. Acta Paediatr Suppl 2007; 96:33-36

124. Fazekas F, Kleinert R, Offenbacher H, et al. Pathologic correlates of incidental MRI white matter signal hyperintensities. Neurology 1993; 43:1683-1689

125. Ginsberg L, Manara R, Valentine AR, et al. Magnetic resonance imaging changes in Fabry disease. Acta Paediatr Suppl 2006; 95:57-62

126. Tedeschi G, Bonavita S, Banerjee TK, et al. Diffuse central neuronal involvement in Fabry disease: a proton MRS imaging study. Neurology 1999; 52:1663-1667

127. Crutchfield KE, Patronas NJ, Dambrosia JM, et al. Quantitative analysis of cerebral vasculopathy in patients with Fabry disease. Neurology 1998; 50:1746-1749

128. Jardim L, Vedolin L, Schwartz IV, et al. CNS involvement in Fabry disease: clinical and imaging studies before and after 12 months of enzyme replacement therapy. J Inherit Metab Dis 2004; 27:229-240

129. Fellgiebel A, Muller MJ, Mazanek M, et al. White matter lesion severity in male and female patients with Fabry disease. Neurology 2005; 65:600-602

130. Buechner S, Moretti M, Burlina AP, et al. Central nervous system involvement in Anderson-Fabry disease: a clinical and MRI retrospective study. J Neurol Neurosurg Psychiatry 2008; 79:1249-1254

131. Schreiber W, Udvardi A, Kristoferitsch W. Chronic meningitis and lacunar stroke in Fabry disease. J Neurol 2007; 254:1447-1449

132. Lidove O, Chauveheid MP, Benoist L, et al. Chronic meningitis and thalamic involvement in a woman: Fabry disease expanding phenotype. J Neurol Neurosurg Psychiatry 2007; 78:1007

133. Moore DF, Ye F, Schiffmann R, Butman JA. Increased signal intensity in the pulvinar on T1-weighted images: a pathognomonic MR imaging sign of Fabry disease. AJNR Am J Neuroradiol 2003; 24:1096-1101

134. Takanashi J, Barkovich AJ, Dillon WP, et al. T1 hyperintensity in the pulvinar: key imaging feature for diagnosis of Fabry disease. AJNR Am J Neuroradiol 2003; 24:916-921

135. Burlina AP, Manara R, Caillaud C, et al. The pulvinar sign: frequency and clinical correlations in Fabry disease. J Neurol 2008; 255:738-744

136. Germain DP, Benistan K, Halimi P. Chiari type I malformation in four unrelated patients affected with Fabry disease. Eur J Med Genet 2006; 49:419-425

137. Germain DP, Avan P, Chassaing A, Bonfils P. Patients affected with Fabry disease have an increased incidence of progressive hearing loss and sudden deafness: an investigation of twenty-two hemizygous male patients. BMC Med Genet 2002; 3:10

138. Sakurai Y, Kojima H, Shiwa M, et al. The hearing status in 12 female and 15 male Japanese Fabry patients. Auris Nasus Larynx 2009; 36:627-632

139. Conti G, Sergi B. Auditory and vestibular findings in Fabry disease: a study of hemizygous males and heterozygous females. Acta Paediatr Suppl 2003; 92:33-37

140. Ries M, Kim HJ, Zalewski CK, et al. Neuropathic and cerebrovascular correlates of hearing loss in Fabry disease. Brain 2007; 130:143-150

141. Palla A, Hegemann S, Widmer U, Straumann D. Vestibular and auditory deficits in Fabry disease and their response to enzyme replacement therapy. J Neurol 2007; 254:1433-1442

142. Orssaud C, Dufier J, Germain DP. Ocular manifestations in Fabry disease: a survey of 32 hemizygous male patients. Ophthalmic Genet 2003; 24:129-139

143. Nguyen TT, Gin T, Nicholls K, et al. Ophthalmological manifestations of Fabry disease: a survey of patients at the Royal Melbourne Fabry Disease Treatment Centre. Clin Experiment Ophthalmol 2005; 33:164-168

144. Sodi A, Ioannidis AS, Mehta A, et al. Ocular manifestations of Fabry’s disease: data from the Fabry Outcome Survey. Br J Ophthalmol 2007; 91:210-214

145. Falke K, Buttner A, Schittkowski M, et al. The microstructure of cornea verticillata in Fabry disease and amiodaroneinduced keratopathy: a confocal laser-scanning microscopy study. Graefes Arch Clin Exp Ophthalmol 2009; 247:523-534

146. Sher NA, Letson RD, Desnick RJ. The ocular manifestations in Fabry’s disease. Arch Ophthalmol 1979; 97:671-676

147. Rosenberg DM, Ferrans VJ, Fulmer JD, et al. Chronic airflow obstruction in Fabry’s disease. Am J Med 1980; 68:898-905

148. Brown LK, Miller A, Bhuptani A, et al. Pulmonary involvement in Fabry disease. Am J Respir Crit Care Med 1997; 155:1004-1010

149. Magage S, Lubanda JC, Germain DP, et al. [Respiratory involvement in patients with Fabry disease]. Med Sci (Paris) 2005; 21:37-39

150. Magage S, Lubanda JC, Susa Z, et al. Natural history of the respiratory involvement in Anderson-Fabry disease. J Inherit Metab Dis 2007; 30:790-799

151. Wang RY, Abe JT, Cohen AH, Wilcox WR. Enzyme replacement therapy stabilizes obstructive pulmonary Fabry disease associated with respiratory globotriaosylceramide storage. J Inherit Metab Dis 2008; Short Report #126

152. Germain DP, Benistan K, Khatchikian L, Mutschler C. [Bone involvement in Fabry disease.]. Med Sci (Paris) 2005; 21:43-44

153. Germain DP, Benistan K, Boutouyrie P, Mutschler C. Osteopenia and osteoporosis: previously unrecognized symptoms of Fabry disease. Clin Genet 2005; 68:93-95

154. Mersebach H, Johansson JO, Rasmussen AK, et al. Osteopenia: a common aspect of Fabry disease. Predictors of bone mineral density. Genet Med 2007; 9:812-818

155. Germain DP. Bone and muscle involvement in Fabry disease. In Fabry disease. Edited by Elstein D, Altarescu G, Beck M. Dordrecht, Heidelberg, Springer; London, New-York, 2010:293-298

156. Sadek J, Shellhaas R, Camfield CS, et al. Psychiatric findings in four female carriers of Fabry disease. Psychiatr Genet 2004; 14:199-201

157. Gold KF, Pastores GM, Botteman MF, et al. Quality of life of patients with Fabry disease. Qual Life Res 2002; 11:317-327

158. Street NJ, Yi MS, Bailey LA, Hopkin RJ. Comparison of health-related quality of life between heterozygous women with Fabry disease, a healthy control population, and patients with other chronic disease. Genet Med 2006; 8:346-353

159. Crosbie TW, Packman W, Packman S. Psychological aspects of patients with Fabry disease. J Inherit Metab Dis 2009; 32:745-753

160. Segal P, Kohn Y, Pollak Y, et al. Psychiatric and cognitive profile in Anderson-Fabry patients: a preliminary study. J Inherit Metab Dis 2010; 33:429-436

161. Laney DA, Gruskin DJ, Fernhoff PM, et al. Social-adaptive and psychological functioning of patients affected by Fabry disease. J Inherit Metab Dis 2010; 33:429-436

162. Kleinert J, Dehout F, Schwarting A, et al. Anemia is a new complication in Fabry disease: data from the Fabry Outcome Survey. Kidney Int 2005; 67:1955-1960

163. Oliveira JP, Valbuena C, Baldaia Moreira A, et al. Splenomegaly, hypersplenism and peripheral blood cytopaenias in patients with classical Anderson-Fabry disease. Virchows Arch 2008; 453:291-300

164. Boutouyrie P, Laurent S, Laloux B, et al. Non-invasive evaluation of arterial involvement in patients affected with Fabry disease. J Med Genet 2001; 38:629-631

165. Boutouyrie P, Laurent S, Laloux B, et al. Arterial remodelling in Fabry disease. Acta Paediatr Suppl 2002; 91:62-66

166. Barbey F, Brakch N, Linhart A, et al. Increased carotid intima-media thickness in the absence of atherosclerotic plaques in an adult population with Fabry disease. Acta Paediatr Suppl 2006; 95:63-68

167. Barbey F, Brakch N, Linhart A, et al. Cardiac and vascular hypertrophy in Fabry disease: evidence for a new mechanism independent of blood pressure and glycosphingolipid deposition. Arterioscler Thromb Vasc Biol 2006; 26:839-844

168. Papaxanthos-Roche A, Deminiere C, Bauduer F, et al. Azoospermia as a new feature of Fabry disease. Fertil Steril 2007; 88:212. e215-218

169. Cox-Brinkman J, Vedder A, Hollak C, et al. Threedimensional face shape in Fabry disease. Eur J Hum Genet 2007; 15:535-542

170. Hauser AC, Gessl A, Lorenz M, et al. High prevalence of subclinical hypothyroidism in patients with Anderson-Fabry disease. J Inherit Metab Dis 2005; 28:715-722

171. Faggiano A, Pisani A, Milone F, et al. Endocrine dysfunction in patients with Fabry disease. J Clin Endocrinol Metab 2006; 91:4319-4325

172. Amann-Vesti BR, Gitzelmann G, Widmer U, et al. Severe lymphatic microangiopathy in Fabry disease. Lymphat Res Biol 2003; 1:185-189

173. Ries M, Bettis KE, Choyke P, et al. Parapelvic kidney cysts: a distinguishing feature with high prevalence in Fabry disease. Kidney Int 2004; 66:978-982

174. Sayer JA, Haslam P, Brennan P. Parapelvic cysts leading to a diagnosis of Fabry disease. Kidney Int 2008; 74:1366

175. Foda MM, Mahmood K, Rasuli P, et al. High-flow priapism associated with Fabry’s disease in a child: a case report and review of the literature. Urology 1996; 48:949-952

176. Backenroth R, Landau EH, Goren M, et al. Fabry disease and G6PD in three family members with priapism: is the nitric oxide pathway to blame? J Sex Med 2010; 7:1588-1591

177. Germain DP. General aspects of X-linked diseases. In Fabry disease. Perspectives from 5 years of FOS. Edited by Mehta AB, Beck M, Sunder-Plassman G. Oxford, Oxford Pharmagenesis; 2006; 63-68

178. Germain DP. [Genetics of Fabry disease: diagnostic and therapeutic implications]. Presse Med 2007; 36:S14-19

179. Lyon MF. Gene action in the X-chromosome of the mouse (mus musculus L.). Nature 1961; 190:372-373

180. Dobyns WB, Filauro A, Tomson BN, et al. Inheritance of most X-linked traits is not dominant or recessive, just X-linked. Am J Med Genet A 2004; 129:136-143

181. Germain DP. [Fabry disease. Clinical and genetic aspects. Therapeutic perspectives]. Rev Med Interne 2000; 21:1086-1103

182. Whybra C, Kampmann C, Willers I, et al. Anderson-Fabry disease: clinical manifestations of disease in female heterozygotes. J Inherit Metab Dis 2001; 24:715-724

183. Whybra C, Wendrich K, Ries M, et al. Clinical manifestations in female Fabry disease patients. Contrib Nephrol 2001; 136:245-250

184. Eng CM, Fletcher J, Wilcox WR, et al. Fabry disease: baseline medical characteristics of a cohort of 1765 males and females in the Fabry Registry. J Inherit Metab Dis 2007; 30:184-192

185. Mutoh T, Senda Y, Sugimura K et al. Severe orthostatic hypotension in a female carrier of Fabry’s disease. Arch Neurol 1988; 45:468-472

186. Galanos J, Nicholls K, Grigg L, et al. Clinical features of Fabry’s disease in Australian patients. Intern Med J 2002; 32:575-584 187. Germain DP. [Fabry disease in 2004]. Rev Prat 2003; 53:2215-2220

187. Igawa O, Miake J, Hisatome I. Ventricular tachycardias and dilated cardiomyopathy caused by Fabry disease. Pacing Clin Electrophysiol 2005; 28:1142-1143

188. Grewal RP, McLatchey SK. Cerebrovascular manifestations in a female carrier of Fabry’s disease. Acta Neurol Belg 1992; 92:36-40

189. Wendrich K, Whybra C, Ries M, et al. Neurological manifestations of Fabry disease in females. Contrib Nephrol 2001; 136:241-244

190. Giacomini PS, Shannon PT, Clarke JT, Jaigobin C. Fabry’s disease presenting as stroke in a young female. Can J Neurol Sci 2004; 31:112-114

191. Kotanko P, Kramar R, Devrnja D, et al. Results of a nationwide screening for Anderson-Fabry disease among dialysis patients. J Am Soc Nephrol 2004; 15:1323-1329

192. Ichinose M, Nakayama M, Ohashi T, et al. Significance of screening for Fabry disease among male dialysis patients. Clin Exp Nephrol 2005; 9:228-232

193. Sachdev B, Takenaka T, Teraguchi H, et al. Prevalence of Anderson-Fabry disease in male patients with late onset hypertrophic cardiomyopathy. Circulation 2002; 105:1407-1411

194. Monserrat L, Gimeno-Blanes JR, Marin F, et al. Prevalence of Fabry disease in a cohort of 508 unrelated patients with hypertrophic cardiomyopathy. J Am Coll Cardiol 2007; 50:2399-2403

195. Hagege AA, Caudron E, Damy T, et al. Screening patients with hypertrophic cardiomyopathy for Fabry disease using a filterpaper test: the FOCUS study. Heart 2010; in press

196. Rolfs A, Bottcher T, Zschiesche M, et al. Prevalence of Fabry disease in patients with cryptogenic stroke: a prospective study. Lancet 2005; 366:1794-1796

197. Brouns R, Sheorajpanday R, Braxel E, et al. Middelheim Fabry Study (MiFaS): a retrospective Belgian study on the prevalence of Fabry disease in young patients with cryptogenic stroke. Clin Neurol Neurosurg 2007; 109:479-484

198. Brouns R, Thijs V, Eyskens F, et al. Belgian Fabry study: prevalence of Fabry disease in a cohort of 1000 young patients with cerebrovascular disease. Stroke 2010; 41:863-868

199. Wozniak MA, Kittner SJ, Tuhrim S, et al. Frequency of unrecognized Fabry disease among young European-American and African-American men with first ischemic stroke. Stroke 2010; 41:78-81

200. Vedder AC, Gerdes VE, Poorthuis BJ, et al. Failure to detect Fabry patients in a cohort of prematurely atherosclerotic males. J Inherit Metab Dis 2007; 30:988

201. Hauser AC, Lorenz M, Voigtlander T, et al. Results of an ophthalmologic screening programme for identification of cases with Anderson-Fabry disease. Ophthalmologica 2004; 218:207- 209

202. Ishii S, Kase R, Sakuraba H, Suzuki Y. Characterization of a mutant alpha-galactosidase gene product for the late-onset cardiac form of Fabry disease. Biochem Biophys Res Commun 1993; 197:1585-1589

203. Ishii S, Chang HH, Kawasaki K, et al. Mutant alphagalactosidase A enzymes identified in Fabry disease patients with residual enzyme activity: biochemical characterization and restoration of normal intracellular processing by 1-deoxygalactonojirimycin. Biochem J 2007; 406:285-295

204. Kleinert J, Kotanko P, Spada M, et al. Anderson-Fabry disease: a case-finding study among male kidney transplant recipients in Austria. Transpl Int 2009; 22:287-292

205. Linthorst GE, Hollak CE, Korevaar JC, et al. alphaGalactosidase A deficiency in Dutch patients on dialysis: a critical appraisal of screening for Fabry disease. Nephrol Dial Transplant 2003; 18:1581-1584

206. Germain DP. A new phenotype of Fabry disease with intermediate severity between the classical form and the cardiac variant. Contrib Nephrol 2001; 136:234-240

207. Germain DP, Benistan K, Angelova L. [X-linked inheritance and its implication in the diagnosis and management of female patients in Fabry disease]. Rev Med Int 2010; 31:S209-S214

208. Sakuraba H, Oshima A, Fukuhara Y, et al. Identification of point mutations in the alpha-galactosidase A gene in classical and atypical hemizygotes with Fabry disease. Am J Hum Genet 1990; 47:784-789

209. Eng CM, Resnick-Silverman LA, Niehaus DJ, et al. Nature and frequency of mutations in the alpha-galactosidase A gene that cause Fabry disease. Am J Hum Genet 1993; 53:1186-1197

210. Eng CM, Desnick RJ. Molecular basis of Fabry disease: mutations and polymorphisms in the human alpha-galactosidase A gene. Hum Mutat 1994; 3:103-111

211. Ploos van Amstel JK, Jansen RP, de Jong JG, et al. Six novel mutations in the alpha-galactosidase A gene in families with Fabry disease. Hum Mol Genet 1994; 3:503-505

212. Blanch LC, Meaney C, Morris CP. A sensitive mutation screening strategy for Fabry disease: detection of nine mutations in the alpha-galactosidase A gene. Hum Mutat 1996; 8:38-43

213. Davies JP, Eng CM, Hill JA, et al. Fabry disease: fourteen alpha-galactosidase A mutations in unrelated families from the United Kingdom and other European countries. Eur J Hum Genet 1996; 4:219-224

214. Germain DP, Biasotto M, Tosi M, et al. Fluorescenceassisted mismatch analysis (FAMA) for exhaustive screening of the alpha-galactosidase A gene and detection of carriers in Fabry disease. Hum Genet 1996; 98:719-726

215. Redonnet-Vernhet I, Ploos van Amstel JK, Jansen RP, et al. Uneven × inactivation in a female monozygotic twin pair with Fabry disease and discordant expression of a novel mutation in the alpha-galactosidase A gene. J Med Genet 1996; 33:682-688

216. Eng CM, Ashley GA, Burgert TS, et al. Fabry disease: thirty-five mutations in the alpha-galactosidase A gene in patients with classic and variant phenotypes. Mol Med 1997; 3:174-182

217. Guffon N, Froissart R, Chevalier-Porst F, Maire I. Mutation analysis in 11 French patients with Fabry disease. Hum Mutat 1998; (Suppl 1):S288-290

218. Germain DP, Poenaru L. Fabry disease: identification of novel alpha-galactosidase A mutations and molecular carrier detection by use of fluorescent chemical cleavage of mismatches. Biochem Biophys Res Commun 1999; 257:708-713.

219. Topaloglu AK, Ashley GA, Tong B, et al. Twenty novel mutations in the alpha-galactosidase A gene causing Fabry disease. Mol Med 1999; 5:806-811

220. Ashton-Prolla P, Tong B, Shabbeer J, et al. Fabry disease: twenty-two novel mutations in the alpha-galactosidase A gene and genotype/phenotype correlations in severely and mildly affected hemizygotes and heterozygotes. J Investig Med 2000; 48:227-235

221. Kase R, Bierfreund U, Klein A, et al. Characterization of two alpha-galactosidase mutants (Q279E and R301Q) found in an atypical variant of Fabry disease. Biochim Biophys Acta 2000; 1501:227-235

222. Lee JK, Kim GH, Kim JS, et al. Identification of four novel mutations in five unrelated Korean families with Fabry disease. Clin Genet 2000; 58:228-233

223. Altarescu GM, Goldfarb LG, Park KY, et al. Identification of fifteen novel mutations and genotype-phenotype relationship in Fabry disease. Clin Genet 2001; 60:46-51

224. Ashley GA, Shabbeer J, Yasuda M, et al. Fabry disease: twenty novel alpha-galactosidase A mutations causing the classical phenotype. J Hum Genet 2001; 46:192-196

225. Blaydon D, Hill J, Winchester B. Fabry disease: 20 novel GLA mutations in 35 families. Hum Mutat 2001; 18:459

226. Germain DP, Salard D, Fellmann F, et al. Identification of a novel de novo mutation (G373D) in the alpha-galactosidase A gene (GLA) in a patient affected with Fabry disease. Hum Mutat 2001; 17:353

227. Germain DP. Co-occurrence and contribution of Fabry disease and Klippel-Trenaunay-Weber syndrome to a patient with atypical skin lesions. Clin Genet 2001; 60:63-67

228. Germain DP, Shabbeer J, Cotigny S, Desnick RJ. Fabry disease: twenty novel alpha-galactosidase A mutations and genotype-phenotype correlations in classical and variant phenotypes. Mol Med 2002; 8:306-312

229. Yasuda M, Shabbeer J, Osawa M, Desnick RJ. Fabry disease: novel alpha-galactosidase A 3’-terminal mutations result in multiple transcripts due to aberrant 3’-end formation. Am J Hum Genet 2003; 73:162-173

230. Garman SC, Garboczi DN. The molecular defect leading to Fabry disease: structure of human alpha-galactosidase. J Mol Biol 2004; 337:319-335

231. Dobrovolny R, Dvorakova L, Ledvinova J, et al. Recurrence of Fabry disease as a result of paternal germline mosaicism for alpha-galactosidase A gene mutation. Am J Med Genet A 2005; 134:84-87

232. Shabbeer J, Robinson M, Desnick RJ. Detection of alpha-galactosidase A mutations causing Fabry disease by denaturing high performance liquid chromatography. Hum Mutat 2005; 25:299-305

233. Schaefer E, Mehta A, Gal A. Genotype and phenotype in Fabry disease: analysis of the Fabry Outcome Survey. Acta Paediatr Suppl 2005; 94:87-92

234. Shabbeer J, Yasuda M, Benson SD, Desnick RJ. Fabry disease: identification of 50 novel alpha-galactosidase A mutations causing the classic phenotype and three-dimensional structural analysis of 29 missense mutations. Hum Genomics 2006; 2:297-309

235. Shimotori M, Maruyama H, Nakamura G, et al. Novel mutations of the GLA gene in Japanese patients with Fabry disease and their functional characterization by active site specific chaperone. Hum Mutat 2008; 29:331

236. Bernstein HS, Bishop DF, Astrin KH, et al. Fabry disease: six gene rearrangements and an exonic point mutation in the alphagalactosidase gene. J Clin Invest 1989; 83:1390-1399

237. Kornreich R, Bishop DF, Desnick RJ. α-Galactosidase A gene rearrangement causing Fabry disease. Identification of short direct repeats at breakpoints in an Alu-rich gene. J Biol Chem 1990; 265:9319-9326

238. Gal A. Molecular genetics of Fabry disease and Genotype-phenotype correlation. In Fabry disease. Edited by Elstein D, Altarescu G, Beck M. Dordrecht, Heidelberg, Springer;London, New-York: 2010:3-19

239. The Human Gene Mutation Database at the Institute of Medical Genetics in Cardiff [http://www.hgmd.cf.ac.uk.]

240. Froissart R, Guffon N, Vanier MT, et al. D313Y is an alphagalactosidase A sequence variant that causes pseudodeficient activity in plasma. Mol Genet Metab 2003; 80:307-314

241. Davies JP, Winchester BG, Malcolm S. Sequence variations in the first exon of alpha-galactosidase A. J Med Genet 1993; 30:658-663

242. Fitzmaurice TF, Desnick RJ, Bishop DF. Human alphagalactosidase A: high plasma activity expressed by the -30G > A allele. J Inherit Metab Dis 1997; 20:643-657

243. Aerts JM, Groener JE, Kuiper S, et al. Elevated globotriaosylsphingosine is a hallmark of Fabry disease. Proc Natl Acad Sci USA 2008; 105:2812-2817

244. Guce AI, Garman SC. The structure of human α-galactosidase A and implications for Fabry disease. In Fabry disease. Edited by Elstein D, Altarescu G, Beck M. Dordrecht, Heidelberg, London, New-York: Springer; 2010:21-38

245. Guce AI, Clark NE, Salgado EN, et al. Catalytic mechanism of human alpha-galactosidase. J Biol Chem 2010; 285:3625- 3632

246. Linthorst GE, De Rie MA, Tjiam KH, et al. Misdiagnosis of Fabry disease: importance of biochemical confirmation of clinical or pathological suspicion. Br J Dermatol 2004; 150:575-577

247. Mayes JS, Scheerer JB, Sifers RN, Donaldson ML. Differential assay for lysosomal alpha-galactosidases in human tissues and its application to Fabry’s disease. Clin Chim Acta 1981; 112:247-251

248. Hoffmann B, Georg Koch H, Schweitzer-Krantz S, et al. Deficient alpha-galactosidase A activity in plasma but no Fabry disease--a pitfall in diagnosis. Clin Chem Lab Med 2005; 43:1276-1277

249. Linthorst GE, Vedder AC, Aerts JM, Hollak CE. Screening for Fabry disease using whole blood spots fails to identify one-third of female carriers. Clin Chim Acta 2005; 353:201-203

250. Chamoles NA, Blanco M, Gaggioli D. Fabry disease: enzymatic diagnosis in dried blood spots on filter paper. Clin Chim Acta 2001; 308:195-196

251. Caudron E, Moliere D, Zhou JY, et al. [Recent advances of Fabry disease screening for at risk population]. Med Sci (Paris) 2005; 21:48-50

252. Lukacs Z, Keil A, Kohlschutter A, et al. The ratio of alphagalactosidase to beta-glucuronidase activities in dried blood for the identification of female Fabry disease patients. J Inherit Metab Dis 2005; 28:803-805

253. Zhang XK, Elbin CS, Chuang WL, et al. Multiplex enzyme assay screening of dried blood spots for lysosomal storage disorders by using tandem mass spectrometry. Clin Chem 2008; 54:1725-1728

254. Olivova P, der Veen KV, Cullen E, et al. Effect of sample collection on alpha-galactosidase A enzyme activity measurements in dried blood spots on filter paper. Clin Chim Acta 2009; 403:159-162

255. Vedder AC, Linthorst GE, van Breemen MJ, et al. The Dutch Fabry cohort: diversity of clinical manifestations and Gb3 levels. J Inherit Metab Dis 2007; 30:68-78

256. Roy S, Gaudin K, Germain DP, et al. Optimisation of the separation of four major neutral glycosphingolipids: application to a rapid and simple detection of urinary globotriaosylceramide in Fabry disease. J Chromatogr B Analyt Technol Biomed Life Sci 2004; 805:331-337

257. Auray-Blais C, Cyr D, Mills K, et al. Development of a filter paper method potentially applicable to mass and high-risk urinary screenings for Fabry disease. J Inherit Metab Dis 2007; 30:106

258. Auray-Blais C, Cyr D, Ntwari A, et al. Urinary globotriaosylceramide excretion correlates with the genotype in children and adults with Fabry disease. Mol Genet Metab 2008;93:331-340

259. Touboul D, Roy S, Germain DP, et al. Fast fingerprinting by MALDI-TOF mass spectrometry of urinary sediment glycosphingolipids in Fabry disease. Anal Bioanal Chem 2005; 382:1209-1216

260. Mills K, Morris P, Lee P, et al. Measurement of urinary CDH and CTH by tandem mass spectrometry in patients hemizygous and heterozygous for Fabry disease. J Inherit Metab Dis 2005; 28:35-48

261. Young E, Mills K, Morris P, et al. Is globotriaosylceramide a useful biomarker in Fabry disease? Acta Paediatr Suppl 2005; 94:51-54

262. Piraud M, de Goiffon F, Froissart R, et al. [Globotriaosylceramide measurement in urine]. Med Sci (Paris) 2005; 21:45-47

263. Hozumi I, Nishizawa M, Ariga T, Miyatake T. Biochemical and clinical analysis of accumulated glycolipids in symptomatic heterozygotes of angiokeratoma corporis diffusum (Fabry’s disease) in comparison with hemizygotes. J Lipid Res 1990; 31:335-340

264. Delobel A, Roy S, Touboul D, et al. Atmospheric pressure photoionization coupled to porous graphitic carbon liquid chromatography for the analysis of globotriaosylceramides. Application to Fabry disease. J Mass Spectrom 2006l;41:50-58

265. Touboul D, Roy S, Germain DP, et al. MALDI-TOF and cluster-TOF-SIMS imaging of Fabry disease biomarkers. Int J Mass Spectrometry 2007; 260:158-165

266. Bishop DF, Calhoun DH, Bernstein HS, et al. Human alpha-galactosidase A: nucleotide sequence of a cDNA clone encoding the mature enzyme. Proc Natl Acad Sci USA 1986; 83:4859-4863

267. Kornreich R, Desnick RJ, Bishop DF. Nucleotide sequence of the human alpha-galactosidase A gene. Nucl Acids Res 1989; 17:3301-3302

268. Rodriguez-Mari A, Coll MJ, Chabas A. Molecular analysis in Fabry disease in Spain: fifteen novel GLA mutations and identification of a homozygous female. Hum Mutat 2003; 22:258

269. Schirinzi A, Centra M, Prattichizzo C, et al. Identification of GLA gene deletions in Fabry patients by Multiplex Ligationdependent Probe Amplification (MLPA). Mol Genet Metab 2008; 94:382-385

270. Bekri S, Lidove O, Jaussaud R, et al. The role of ceramide trihexoside (globotriaosylceramide) in the diagnosis and followup of the efficacy of treatment of Fabry disease: a review of the literature. Cardiovasc Hematol Agents Med Chem 2006; 4:289-297

271. Andrade J, Waters PJ, Singh RS, et al. Screening for Fabry disease in patients with chronic kidney disease: limitations of plasma alpha-galactosidase assay as a screening test. Clin J Am Soc Nephrol 2008; 3:139-145

272. Li Y, Scott CR, Chamoles NA, et al. Direct multiplex assay of lysosomal enzymes in dried blood spots for newborn screening. Clin Chem 2004; 50:1785-1796

273. Gelb MH, Turecek F, Scott CR, Chamoles NA. Direct multiplex assay of enzymes in dried blood spots by tandem mass spectrometry for the newborn screening of lysosomal storage disorders. J Inherit Metab Dis 2006; 29:397-404

274. Navarro C, Teijeira S, Dominguez C, et al. Fabry disease: an ultrastructural comparative study of skin in hemizygous and heterozygous patients. Acta Neuropathol 2006; 111:178-185

275. Albay D, Adler SG, Philipose J, et al. Chloroquine-induced lipidosis mimicking Fabry disease. Mod Pathol 2005; 733-738

276. Demuth K, Germain DP. Endothelial markers and homocysteine in patients with classic Fabry disease. Acta Paediatr Suppl 2002; 91:57-61

277. Cartwright DJ, Cole AL, Cousins AJ, Lee PJ. Raised HDL cholesterol in Fabry disease: response to enzyme replacement therapy. J Inherit Metab Dis 2004; 27:791-793

278. Vedder AC, Cox-Brinkman J, Hollak CE, et al. Plasma chitotriosidase in male Fabry patients: a marker for monitoring lipid-laden macrophages and their correction by enzyme replacement therapy. Mol Genet Metab 2006; 89:239-244

279. van Breemen MJ, Rombach SM, Dekker N, et al. Reduction of elevated plasma globotriaosylsphingosine in patients with classic Fabry disease following enzyme replacement therapy. Biochim Biophys Acta 2010; in press

280. Rombach SM, Dekker N, Bouwman MG, et al. Plasma globotriaosylsphingosine: Diagnostic value and relation to clinical manifestations of Fabry disease. Biochim Biophys Acta 2010’ 180:741-748

281. Togawa T, Kodama T, Suzuki T, et al. Plasma globotriaosylsphingosine as a biomarker of Fabry disease. Mol Genet Metab 2010; 100:257-261

282. Auray-Blais C, Ntwari A, Clarke JT, et al. How well does urinary lyso-Gb3 function as a biomarker in Fabry disease? Clin Chim Acta 2010; 411:1906-1914

283. Sanchez-Nino MD, Sanz AB, Carrasco S, et al. Globotriaosylsphingosine actions on human glomerular podocytes: implications for Fabry nephropathy. Nephrol Dial Transplant 2010; in press

284. Brakch N, Dormond O, Bekri S, et al. Evidence for a role of sphingosine-1 phosphate in cardiovascular remodelling in Fabry disease. Eur Heart J 2010’ 31:67-76

285. Lacomis D, Roeske-Anderson L, Mathie L. Neuropathy and Fabry’s disease. Muscle Nerve 2005;31:102-107

286. Saip S, Uluduz D, Erkol G. Fabry disease mimicking multiple sclerosis. Clin Neurol Neurosurg 2007; 109:361-363

287. Linthorst GE, Hollak CE. Chloroquine-induced phospholipidosis of the kidney mimicking Fabry’s disease. Hum Pathol 2003; 34:1358

288. Bennett RL, Hart KA, O’Rourke E, et al. Fabry disease in genetic counseling practice: recommendations of the National Society of Genetic Counselors. J Genet Couns 2002; 11:121-146

289. Laney DA, Fernhoff PM. Diagnosis of Fabry disease via analysis of family history. J Genet Couns 2008; 17:79-83

290. Desnick RJ. Prenatal diagnosis of Fabry disease. Prenat Diagn 2007; 27:693-694

291. Desnick RJ, Brady R, Barranger J, et al. Fabry disease, an under-recognized multisystemic disorder: expert recommendations for diagnosis, management, and enzyme replacement therapy. Ann Intern Med 2003; 138:338-346

292. Mehta A, Ricci R, Widmer U, et al. Fabry disease defined: baseline clinical manifestations of 366 patients in the Fabry Outcome Survey. Eur J Clin Invest 2004; 34:236-242

293. Beck M. Agalsidase alfa - a preparation for enzyme replacement therapy in Anderson-Fabry disease. Expert Opin Investig Drugs 2002; 11:851-858

294. Germain DP. Fabry disease: recent advances in enzyme replacement therapy. Expert Opin Investig Drugs 2002; 11:1467- 1476

295. Desnick RJ. Enzyme replacement therapy for Fabry disease: lessons from two alpha-galactosidase A orphan products and one FDA approval. Expert Opin Biol Ther 2004; 4:1167-1176

296. Beck M. Agalsidase alfa for the treatment of Fabry disease: new data on clinical efficacy and safety. Expert Opin Biol Ther 2009; 9:255-261

297. Morel CF, Clarke JT. The use of agalsidase alfa enzyme replacement therapy in the treatment of Fabry disease. Expert Opin Biol Ther 2009; 9:631-639

298. Germain DP. [Fabry’s disease (alpha-galactosidase-A deficiency): recent therapeutic innovations]. J Soc Biol 2002; 196:183-190

299. Germain DP. [Current practice in Fabry disease: a comprehensive multidisciplinary approach]. Presse Med 2007; 36:S3-6

300. Weidemann F, Sommer C, Duning T, et al. Departmentrelated tasks and organ-targeted therapy in Fabry disease: an interdisciplinary challenge. Am J Med 2010; 123:658e1-658e10

301. Gordon KE, Ludman MD, Finley GA. Successful treatment of painful crises of Fabry disease with low dose morphine. Pediatr Neurol 1995; 12:250-251

302. Lenoir G, Rivron M, Gubler MC et al. [Fabry’s disease. Carbamazepine therapy in acrodyniform syndrome]. Arch Fr Pediatr 1977; 34:704-716

303. Filling-Katz MR, Merrick HF, Fink JK, et al. Carbamazepine in Fabry’s disease: effective analgesia with dose- dependent exacerbation of autonomic dysfunction. Neurology 1989; 39:598-600

304. Ries M, Mengel E, Kutschke G, et al. Use of gabapentin to reduce chronic neuropathic pain in Fabry disease. J Inherit Metab Dis 2003; 26:413-414

305. Lockman LA, Hunninghake DB, Krivit W, Desnick RJ. Relief of pain of Fabry’s disease by diphenylhydantoin. Neurology 1973; 23:871-875

306. Argoff CE, Barton NW, Brady RO, Ziessman HA. Gastrointestinal symptoms and delayed gastric emptying in Fabry’s disease: response to metoclopramide. Nucl Med Commun 1998; 19:887-891

307. Warnock DG. Fabry disease: diagnosis and management, with emphasis on the renal manifestations. Curr Opin Nephrol Hypertens 2005; 14:87-95

308. Germain DP, Waldek S, Banikazemi M, et al. Sustained, long-term renal stabilization after 54 months of agalsidase beta therapy in patients with Fabry disease. J Am Soc Nephrol 2007; 18:1547-1557

309. Wanner C, Breunig F. Fabry nephropathy and the case for adjunctive renal therapy. J Am Soc Nephrol 2007; 18:2426-2428

310. Warnock DG, Remuzzi G, Brenner BM, et al. Introduction to Focus on Fabry nephropathy: biomarkers, progression, and disease severity. Clin J Am Soc Nephrol 2010; 5:359

311. Tahir H, Jackson LL, Warnock DG. Antiproteinuric therapy and Fabry nephropathy: sustained reduction of proteinuria in patients receiving enzyme replacement therapy with agalsidase-beta. J Am Soc Nephrol 2007; 18:2609-2617

312. Kleinert J, Dehout F, Schwarting A, et al. Prevalence of uncontrolled hypertension in patients with Fabry disease. Am J Hypertens 2006; 19:782-787

313. Thadhani R, Wolf M, West ML, et al. Patients with Fabry disease on dialysis in the United States. Kidney Int 2002; 61:249- 255

314. Mignani R, Feriozzi S, Pisani A, et al. Agalsidase therapy in patients with Fabry disease on renal replacement therapy: a nationwide study in Italy. Nephrol Dial Transplant 2008; 23:1628-1635

315. Cybulla M, Walter KN, Schwarting A, et al. Kidney transplantation in patients with Fabry disease. Transpl Int 2009; 22:475-481

316. Ojo A, Meier-Kriesche HU, Friedman G, et al. Excellent outcome of renal transplantation in patients with Fabry‘s disease. Transplantation 2000; 69:2337-2339

317. Shah T, Gill J, Malhotra N, et al. Kidney transplant outcomes in patients with Fabry disease. Transplantation 2009; 87:280-285

318. Politei JM. Can we use statins to prevent stroke in Fabry disease? J Inherit Metab Dis 2009; 32:481-487

319. Cantor WJ, Daly P, Iwanochko M, et al. Cardiac transplantation for Fabry’s disease. Can J Cardiol 1998; 14:81-84

320. Lee K, Jin X, Zhang K, et al. A biochemical and pharmacological comparison of enzyme replacement therapies for the glycolipid storage disorder Fabry disease. Glycobiology 2003; 13:305-313

321. Sakuraba H, Murata-Ohsawa M, Kawashima I, et al. Comparison of the effects of agalsidase alfa and agalsidase beta on cultured human Fabry fibroblasts and Fabry mice. J Hum Genet 2006; 51:180-188

322. Eng CM, Guffon N, Wilcox WR, et al. Safety and efficacy of recombinant human α-galactosidase A - replacement therapy in Fabry’s disease. N Engl J Med 2001; 345:9-16

323. Schiffmann R, Kopp JB, Austin HA, et al. Enzyme replacement therapy in Fabry disease: a randomized controlled trial. JAMA 2001; 285:2743-2749

324. Banikazemi M, Bultas J, Waldek S, et al. Agalsidase-beta therapy for advanced Fabry disease: a randomized trial. Ann Intern Med 2007; 146:77-86

325. Hughes DA, Elliott PM, Shah J, et al. Effects of enzyme replacement therapy on the cardiomyopathy of Anderson-Fabry disease: a randomised, double-blind, placebo-controlled clinical trial of agalsidase alfa. Heart 2008; 94:153-158

326. Schiffmann R, Ries M, Timmons M, et al. Long-term therapy with agalsidase alfa for Fabry disease: safety and effects on renal function in a home infusion setting. Nephrol Dial Transplant 2006; 21:345-354

327. Schiffmann R, Askari H, Timmons M et al. Weekly enzyme replacement therapy may slow decline of renal function in patients with Fabry disease who are on long-term biweekly dosing. J Am Soc Nephrol 2007; 18:1576-1583

328. Wilcox WR, Banikazemi M, Guffon N, et al. Long-term safety and efficacy of enzyme replacement therapy for Fabry’s Disease. Am J Hum Genet 2004; 75:65-74

329. Beck M, Ricci R, Widmer U, et al. Fabry disease: overall effects of agalsidase alfa treatment. Eur J Clin Invest 2004; 34:838-844

330. Hoffmann B, Garcia de Lorenzo A, Mehta A, et al. Effects of enzyme replacement therapy on pain and health related quality of life in patients with Fabry disease: data from FOS (Fabry Outcome Survey). J Med Genet 2005; 42:247-252

331. Schwarting A, Dehout F, Feriozzi S, et al. Enzyme replacement therapy and renal function in 201 patients with Fabry disease. Clin Nephrol 2006; 66:77-84

332. Mehta A, Beck M, Elliott P, et al. Enzyme replacement therapy with agalsidase alfa in patients with Fabry’s disease: an analysis of registry data. Lancet 2009; 374:1886-1896

333. Breunig F, Weidemann F, Strotmann J, et al. Clinical benefit of enzyme replacement therapy in Fabry disease. Kidney Int 2006; 69:1216-1221

334. Kalliokoski RJ, Kantola I, Kalliokoski KK, et al. The effect of 12-month enzyme replacement therapy on myocardial perfusion in patients with Fabry disease. J Inherit Metab Dis 2006; 29:112-118

335. Vedder AC, Linthorst GE, Houge G, et al. Treatment of Fabry disease: outcome of a comparative trial with agalsidase alfa or beta at a dose of 0.2 mg/kg. PLoS One 2007; 2:e598

336. Vedder AC, Breunig F, Donker-Koopman WE, et al. Treatment of Fabry disease with different dosing regimens of agalsidase: effects on antibody formation and GL-3. Mol Genet Metab 2008; 94:319-325

337. Weidemann F, Niemann M, Breunig F, et al. Long-term effects of enzyme replacement therapy on Fabry cardiomyopathy: evidence for a better outcome with early treatment. Circulation 2009; 119:524-529

338. Fabrazyme (agalsidase beta) European Public Assessment Report (EPAR) Replagal (agalsidase alfa) European Public Assessment Report (EPAR) [http://www.emea.europa.eu/humandocs/Humans/EPAR/fabrazyme fabrazyme.htm.]

339. Replagal (agalsidase alfa) European Public Assessment Report (EPAR). [http://www.emea.europa.eu/humandocs Humans/EPAR/replagal/replagal.htm].

340. Pastores GM, Thadani R. Advances in the management of Anderson-Fabry disease: enzyme replacement therapy. Expert Opin Biol Ther 2002; 2:1-9

341. Ries M, Clarke JT, Whybra C, et al. Enzyme-replacement therapy with agalsidase alfa in children with Fabry disease. Pediatrics 2006; 118:924-932

342. Ramaswami U, Wendt S, Pintos-Morell G, et al. Enzyme replacement therapy with agalsidase alfa in children with Fabry disease. Acta Paediatr 2007; 96:122-127

343. Pintos-Morell G, Beck M. Fabry disease in children and the effects of enzyme replacement treatment. Eur J Pediatr 2009; 168:1355-1363

344. Ries M, Clarke JT, Whybra C, et al. Enzyme replacement in Fabry disease: pharmacokinetics and pharmacodynamics of agalsidase alpha in children and adolescents. J Clin Pharmacol 2007; 47:1222-1230

345. Schiffmann R, Martin RA, Reimschisel T, et al. Four-year prospective clinical trial of agalsidase alfa in children with Fabry disease. J Pediatr 2010; 156:832-837

346. Jardim LB, Gomes I, Netto CB, et al. Improvement of sympathetic skin responses under enzyme replacement therapy in Fabry disease. J Inherit Metab Dis 2006; 29:653-659

347. Dehout F, Schwarting A, Beck M, et al. Effects of enzyme replacement therapy with agalsidase alfa on glomerular filtration rate in patients with Fabry disease: preliminary data. Acta Paediatr Suppl 2003; 92:14-15

348. Feriozzi S, Schwarting A, Sunder-Plassmann G, et al. Agalsidase alfa slows the decline in renal function in patients with Fabry disease. Am J Nephrol 2008; 29:353-361

349. West M, Nicholls K, Mehta A, et al. Agalsidase alfa and kidney dysfunction in Fabry disease. J Am Soc Nephrol 2009; 20:1132-1139

350. Baehner F, Kampmann C, Whybra C, et al. Enzyme replacement therapy in heterozygous females with Fabry disease: results of a phase IIIB study. J Inherit Metab Dis 2003; 26:617-627

351. Germain DP. Fabry disease: the need to stratify patient populations to better understand the outcome of enzyme replacement therapy. Clin Ther 2007; 29:S17-S18.

352. Brady RO, Schiffmann R. Enzyme-replacement therapy for metabolic storage disorders. Lancet Neurol 2004; 3:752-756

353. Whybra C, Kampmann C, Krummenauer F et al. The Mainz Severity Score Index: a new instrument for quantifying the Anderson-Fabry disease phenotype, and the response of patients to enzyme replacement therapy. Clin Genet 2004; 65:299-307.

354. Parini R, Rigoldi M, Santus F, et al. Enzyme replacement therapy with agalsidase alfa in a cohort of Italian patients with Anderson-Fabry disease: testing the effects with the Mainz Severity Score Index. Clin Genet 2008; 74:260-266.

355. Whybra C, Miebach E, Mengel E, et al. A 4-year study of the efficacy and tolerability of enzyme replacement therapy with agalsidase alfa in 36 women with Fabry disease. Genet Med 2009; 11:441-449.

356. Thurberg BL, Rennke H, Colvin RB, et al. Globotriaosylceramide accumulation in the Fabry kidney is cleared from multiple cell types after enzyme replacement therapy. Kidney Int 2002; 62:1933-1946.

357. Eto Y, Ohashi T, Utsunomiya Y, et al. Enzyme replacement therapy in Japanese Fabry disease patients: the results of a phase 2 bridging study. J Inherit Metab Dis 2005; 28:575-583.

358. Thurberg BL, Fallon JT, Mitchell R, et al. Cardiac microvascular pathology in Fabry disease: evaluation of endomyocardial biopsies before and after enzyme replacement therapy. Circulation 2009; 119:2561-2567.

359. Schiffmann R, Rapkiewicz A, Abu-Asab M, et al. Pathological findings in a patient with Fabry disease who died after 2.5 years of enzyme replacement. Virchows Arch 2006; 448:337-343

360. Keslova-Veselikova J, Hulkova H, Dobrovolny R, et al. Replacement of alpha-galactosidase A in Fabry disease: effect on fibroblast cultures compared with biopsied tissues of treated patients. Virchows Arch 2008; 452:651-665.

361. Wraith JE, Tylki-Szymanska A, Guffon N, et al. Safety and efficacy of enzyme replacement therapy with agalsidase beta: an international, open-label study in pediatric patients with Fabry disease. J Pediatr 2008; 152:563-570

362. Hilz MJ, Brys M, Marthol H, et al. Enzyme replacement therapy improves function of C-, Adelta-, and Abeta-nerve fibers in Fabry neuropathy. Neurology 2004; 62:1066-1072.

363. Watt T, Burlina AP, Cazzorla C, et al. Agalsidase beta treatment is associated with improved quality of life in patients with Fabry disease: Findings from the Fabry Registry. Genet Med 2010; in press

364. Lindeman RD, Tobin J, Shock NW. Longitudinal studies on the rate of decline in renal function with age. J Am Geriatr Soc 1985; 33:278-285

365. Koskenvuo JW, Hartiala JJ, Nuutila P, et al. Twentyfour-month alpha-galactosidase A replacement therapy in Fabry disease has only minimal effects on symptoms and cardiovascular parameters. J Inherit Metab Dis 2008; 31:432-441

366. Imbriaco M, Pisani A, Spinelli L, et al. Effects of enzymereplacement therapy in patients with Anderson-Fabry disease: a prospective long-term cardiac magnetic resonance imaging study. Heart 2009; 95:1103-1107

367. Lubanda JC, Anijalg E, Bzduch V, et al. Evaluation of a low dose, after a standard therapeutic dose, of agalsidase beta during enzyme replacement therapy in patients with Fabry disease. Genet Med 2009; 11:256-264

368. Mehta A, Beck M, Kampmann C, et al. Enzyme replacement therapy in Fabry disease: comparison of agalsidase alfa and agalsidase beta. Mol Genet Metab 2008; 95:114-115

369. Sirrs S, Clarke JT, Bichet DG, et al. Baseline characteristics of patients enrolled in the Canadian Fabry Disease Initiative. Mol Genet Metab 2010;, 99:367-373

370. Linthorst GE, Hollak CE, Donker-Koopman WE, et al. Enzyme therapy for Fabry disease: neutralizing antibodies toward agalsidase alpha and beta. Kidney Int 2004; 66:1589-1595

371. Benichou B, Goyal S, Sung C, et al. A retrospective analysis of the potential impact of IgG antibodies to agalsidase beta on efficacy during enzyme replacement therapy for Fabry disease. Mol Genet Metab 2009; 96:4-12

372. Stevens LA, Coresh J, Greene T, Levey AS. Assessing kidney function measured and estimated glomerular filtration rate. N Engl J Med 2006; 354:2473-2483

373. Waldek S, Germain DP, Wanner C, Warnock DG. Enzyme replacement therapy for Fabry’s disease. Lancet 2010 ; 375:1523

374. Centre de référence pour la maladie de Fabry et les maladies héréditaires du tissu conjonctif [http://www.centre-geneo. com]

375. Bodensteiner D, Scott CR, Sims KB, et al. Successful reinstitution of agalsidase beta therapy in Fabry disease patients with previous IgE-antibody or skin-test reactivity to the recombinant enzyme. Genet Med 2008; 10:353-358

376. Ohashi T, Iizuka S, Ida H, Eto Y. Reduced alpha-Gal A enzyme activity in Fabry fibroblast cells and Fabry mice tissues induced by serum from antibody positive patients with Fabry disease. Mol Genet Metab 2008; 94:313-318

377. Germain DP. Gaucher’s disease: a paradigm for interventional genetics. Clin Genet 2004;, 65:77-86

378. Germain DP, Puech JP, Caillaud C, et al. Exhaustive screening of the acid beta-glucosidase gene, by fluorescenceassisted mismatch analysis using universal primers: mutation profile and genotype/phenotype correlations in Gaucher disease. Am J Hum Genet 1998; 63:415-427

379. Germain DP, Kaneski CR, Brady RO. Mutation analysis of the acid beta-glucosidase gene in a patient with type 3 Gaucher disease and neutralizing antibody to alglucerase. Mutat Res 2001; 483:89-94

380. Garman RD, Munroe K, Richards SM. Methotrexate reduces antibody responses to recombinant human alpha-galactosidase A therapy in a mouse model of Fabry disease. Clin Exp Immunol 2004; 137:496-502

381. Kosch M, Koch HG, Oliveira JP, et al. Enzyme replacement therapy administered during hemodialysis in patients with Fabry disease. Kidney Int 2004; 66:1279-1282

382. Wendt S, Whybra C, Kampmann C, et al. Successful pregnancy outcome in a patient with Fabry disease receiving enzyme replacement therapy with agalsidase alfa. J Inherit Metab Dis 2005; 28:787-788

383. Kalkum G, Macchiella D, Reinke J, et al. Enzyme replacement therapy with agalsidase alfa in pregnant women with Fabry disease. Eur J Obstet Gynecol Reprod Biol 2009; 144:92-93

384. Germain DP, Bruneval P, Tran TC, et al. Uneventful pregnancy outcome after enzyme replacement therapy with agalsidase beta in a heterozygous female with Fabry disease: A case report. Eur J Med Genet 2010; 53:111-112

385. Politei JM. Treatment with agalsidase beta during pregnancy in Fabry disease. J Obstet Gynaecol Res 2010; 36:428-429

386. Cousins A, Lee P, Rorman D, et al. Home-based infusion therapy for patients with Fabry disease. Br J Nurs 2008; 17:653-657

387. Linthorst GE, Vedder AC, Ormel EE, et al. Home treatment for Fabry disease: practice guidelines based on 3 years experience in The Netherlands. Nephrol Dial Transplant 2006; 21:355-360

388. Thomaidis T, Relle M, Golbas M, et al. Downregulation of alpha-galactosidase A upregulates CD77: functional impact for Fabry nephropathy. Kidney Int 2009; 75:399-407

389. Pastores GM, Hughes DA. To see a world in a grain of sand: elucidating the pathophysiology of Anderson-Fabry disease through investigations of a cellular model. Kidney Int 2009; 75:351-353

390. Suzuki K, Proia RL. Mouse models of human lysosomal diseases. Brain Pathol 1998; 8:195-215

391. Ohshima T, Murray GJ, Swaim WD, et al. Alpha-galactosidase A deficient mice: a model of Fabry disease. Proc Natl Acad Sci USA 1997; 94:2540-2544

392. Gotlib RW, Bishop DF, Wang AM, et al. The entire genomic sequence and cDNA expression of mouse alpha-galactosidase A. Biochem Mol Med 1996; 57:139-148

393. Ishii S, Yoshioka H, Mannen K, et al. Transgenic mouse expressing human mutant alpha-galactosidase A in an endogenous enzyme deficient background: a biochemical animal model for studying active-site specific chaperone therapy for Fabry disease. Biochim Biophys Acta 2004; 1690:250-257

394. Shimmoto M, Kase R, Itoh K, et al. Generation and characterization of transgenic mice expressing a human mutant alpha-galactosidase with an R301Q substitution causing a variant form of Fabry disease. FEBS Lett 1997; 417:89-91

395. Eitzman DT, Bodary PF, Shen Y, et al. Fabry disease in mice is associated with age-dependent susceptibility to vascular thrombosis. J Am Soc Nephrol 2003; 14:298-302

396. Shu L, Park JL, Byun J, et al. Decreased nitric oxide bioavailability in a mouse model of Fabry disease. J Am Soc Nephrol 2009; 20:1975-1985

397. Ohshima T, Schiffmann R, Murray GJ, et al. Aging accentuates and bone marrow transplantation ameliorates metabolic defects in Fabry disease mice. Proc Natl Acad Sci USA 1999; 96:6423-6427

398. Abe A, Gregory S, Lee L, et al. Reduction of globotriaosylceramide in Fabry disease mice by substrate deprivation. J Clin Invest 2000; 105:1563-1571

399. Ioannou YA, Zeidner KM, Gordon RE, Desnick RJ. Fabry disease: preclinical studies demonstrate the effectiveness of alpha-galactosidase A replacement in enzyme-deficient mice. Am J Hum Genet 2001; 68:14-25

400. Ishii S, Chang HH, Yoshioka H, et al. Preclinical efficacy and safety of 1-deoxygalactonojirimycin in mice for Fabry disease. J Pharmacol Exp Ther 2009; 328:723-731

401. Takenaka T, Murray GJ, Qin G, et al. Long-term enzyme correction and lipid reduction in multiple organs of primary and secondary transplanted Fabry mice receiving transduced bone marrow cells. Proc Natl Acad Sci USA 2000; 97:7515-7520

402. Jung SC, Han IP, Limaye A, et al. Adeno-associated viral vector-mediated gene transfer results in long-term enzymatic and functional correction in multiple organs of Fabry mice. Proc Natl Acad Sci USA 2001; 98:2676-2681

403. Takahashi H, Hirai Y, Migita M, et al. Long-term systemic therapy of Fabry disease in a knockout mouse by adeno-associated virus-mediated muscle-directed gene transfer. Proc Natl Acad Sci USA 2002; 99:13777-13782

404. Park J, Murray GJ, Limaye A, et al. Long-term correction of globotriaosylceramide storage in Fabry mice by recombinant adeno-associated virus-mediated gene transfer. Proc Natl Acad Sci USA 2003; 100:3450-3454

405. Nakamura G, Maruyama H, Ishii S, et al. Naked plasmid DNA-based alpha-galactosidase A gene transfer partially reduces systemic accumulation of globotriaosylceramide in Fabry mice. Mol Biotechnol 2008; 38:109-119

406. Koeberl DD. Age-related efficacy with an AAV vector in Fabry disease mice. Mol Genet Metab 2009; 96:83-84

407. Fabry Registry [http://www.lsdregistry.net/fabryregistry]

408. Fabry Outcome Survey [http://www.globaloutcomesurveys.com]

409. Deegan PB, Baehner AF, Barba Romero MA, et al. Natural history of Fabry disease in females in the Fabry Outcome Survey. J Med Genet 2006; 43:347-352

410. Giannini EH, Mehta AB, Hilz MJ, et al. A validated disease severity scoring system for Fabry disease. Mol Genet Metab 2010; 99:283-290

411. Ortiz A, Cianciaruso B, Cizmarik M, et al. End-stage renal disease in patients with Fabry disease: natural history data from the Fabry Registry. Nephrol Dial Transplant 2010; 25:769-775

412. Tomasic IB, Metcalf MC, Guce AI, et al. Interconversion of the specificities of human lysosomal enzymes associated with Fabry and Schindler diseases. J Biol Chem 2010; 285:21560-21566

413. Tajima Y, Kawashima I, Tsukimura T, et al. Use of a modified alpha-N-acetylgalactosaminidase in the development of enzyme replacement therapy for Fabry disease. Am J Hum Genet 2009; 85:569-580

414. Garman SC. Structure-function relationships in alphagalactosidase A. Acta Paediatr Suppl 2007; 96:6-16

415. Yam GH, Zuber C, Roth J. A synthetic chaperone corrects the trafficking defect and disease phenotype in a protein misfolding disorder. FASEB J 2005; 19:12-18

416. Yam GH, Bosshard N, Zuber C, et al. Pharmacological chaperone corrects lysosomal storage in Fabry disease caused by trafficking-incompetent variants. Am J Physiol Cell Physiol 2006; 290:C1076-1082

417. Fan JQ, Ishii S. Active-site-specific chaperone therapy for Fabry disease. Yin and Yang of enzyme inhibitors. FEBS J 2007; 274:4962-4971

418. Germain DP, Fan JQ. Pharmacological chaperone therapy by active-site-specific chaperones in Fabry disease: in vitro and preclinical studies. Int J Clin Pharmacol Ther 2009; 47:S111-117

419. Okumiya T, Ishii S, Takenaka T, et al. Galactose stabilizes various missense mutants of alpha-galactosidase in Fabry disease. Biochem Biophys Res Commun 1995; 214:1219-1224

420. Fan JQ, Ishii S, Asano N, Suzuki Y. Accelerated transport and maturation of lysosomal a-galactosidase A in Fabry lymphoblasts by an enzyme inhibitor. Nature Med 1999; 5:112-115

421. Frustaci A, Chimenti C, Ricci R, et al. Improvement in cardiac function in the cardiac variant of Fabry’s disease with galactose-infusion therapy. N Engl J Med 2001; 345:25-32

422. Sugawara K, Tajima Y, Kawashima I, et al. Molecular interaction of imino sugars with human alpha-galactosidase: Insight into the mechanism of complex formation and pharmacological chaperone action in Fabry disease. Mol Genet Metab 2009; 96:233-238

423. Benjamin ER, Flanagan JJ, Schilling A, et al. The pharmacological chaperone 1-deoxygalactonojirimycin increases alpha-galactosidase A levels in Fabry patient cell lines. J Inherit Metab Dis 2009; 32:424-440

424. MacDermot KD, Holmes A, Miners AH. Anderson-Fabry disease: clinical manifestations and impact of disease in a cohort of 98 hemizygous males. J Med Genet 2001; 38:750-760

425. Ozkara HA, Topcu M. Sphingolipidoses in Turkey. Brain Dev 2004; 26:363-366

426. Pinto R, Caseiro C, Lemos M, et al. Prevalence of lysosomal storage diseases in Portugal. Eur J Hum Genet 2004; 12:87-92