Orphanic hereditary hypophosphatemic rachit with hypercalciuria, nephrocalcinosis on account of mutation gene SLC34A3(Review and case report)
https://doi.org/10.36485/1561-6274-2021-25-3-52-60
Abstract
Orphan Hereditary Hypophosphatemic Rickets with Hypercalciuria (HHRH) (OMIM: 241530; ORPHA: 157215) with an autosomal recessive mode of inheritance occurs with an estimated prevalence of 1: 250,000 in the child population. HHRH was first described by M. Tieder, et al. (1985). The syndrome is caused by heterozygous or homozygous mutations in the SLC34A3 gene mapped to chromosome 9q34.3, which encodes a type II sodium phosphate cotransporter (NaPiIIc). Mutations result in loss of NaPi-IIc function and impairment of phosphate reabsorption in the proximal renal nephron. HHRH is characterized by a decrease in phosphate reabsorption in the proximal nephron tubules, manifested by hyperphosphaturia, hypercalciuria, hypophosphatemia, an increase in the concentration of 1,25(OH) 2D3, a decrease in parathyroid hormone (PTH) circulating in the blood, osteomalacia, inhibition of growth, low corrosiveness, low corrosiveness. The article presents the characteristics of the phenotype and genotype of HHRH, diagnostic criteria and treatment strategy. A description of a clinical case of HHRH with hypercalciuria, nephrocalcinosis and urolithiasis due to mutation of the SLC34A3gene is presented.
About the Authors
Zh. G. Leviashvili
Saint-Petersburg State Pediatric Medical University
Russian Federation
Russian Federation
Prof. Leviashvili Zhanna Gavrilovna, MD, PhD, PROF.DMedSci
Affiliations, Head of the Department of Faculty Pediatrics
194100, St. Petersburg, Litovskaya d. 2.
Phone: (812) 4165286
N. D. Savenkova
Saint-Petersburg State Pediatric Medical University
Russian Federation
Russian Federation
Prof. Savenkova Nadezhda Dmitrievna, MD, PhD, DMedSci
Affiliations, Head of the Department of faculty pediatrics.
194100, St-Petersburg, Litovskaya st., 2.
Phone: (812)4165286
O. V. Lyubimova
Saint-Petersburg State Pediatric Medical University
Russian Federation
Russian Federation
Lyubimova Olga Viktorovna, MD, Head of the Nephrology Department of the University Clinic Affiliations
194100, Saint Petersburg, Litovskaya str., 2
N. L. Levi
Saint-Petersburg State Pediatric Medical University
Russian Federation
Russian Federation
Levi Nazi Lvovna Senior Affiliations, Department of Faculty Pediatrics, Medical Laboratory Assistant
194100, Saint Petersburg, Litovskaya str., 2.
M. О. Amiryan
Saint-Petersburg State Pediatric Medical University
Russian Federation
Russian Federation
Amiryan Margarita Oganesovna, MD Affiliations, Department of Faculty Pediatrics, Senior Medical Laboratory Assistant
194100, St.Petersburg, Litovskaya st. 2.
T. V. Karpova
Saint-Petersburg State Pediatric Medical University
Russian Federation
Russian Federation
Karpova Tatiana Victorovna, MD, Head of the Nephrology Unite of the University Clinic, hea
194100, St. Petersburg, Litovskaya str., 2.
References
1. ORPHAhttps://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=15721 [Electronic resource].20212. OMIM https://www.omim.org/entry/241530 [Electronic resource]2021
2. Bergwitz C, Miyamoto KI. Hereditary hypophosphatemic rickets with hypercalciuria: pathophysiology, clinical presentation, diagnosis and therapy. Pflugers Arch2019;471(1):149–163. doi: 10.1007/s00424-018-2184-2
3. Miyamoto K, Segawa H, Ito M, Kuwahata M Physiological regulation of renal sodium-dependent phosphate cotransporters. Jpn J Physiol2004; 54 (2): 93–102. doi: 10.2170/ jjphysiol.54.93
4. Bergwitz C, Roslin NM, Tieder M, Loredo-Osti JC et al. SLC34A3 mutations in patients with hereditary hypophosphatemic rickets with hypercalciuria predict a key role for the sodium-phosphate cotransporter NaPi-IIc in maintaining phosphate homeostasis. Am J Hum Genet 2006;78(2):179–192. doi: 10.1086/499409
5. Dasgupta D, Wee MJ, Reyes M, Li Y et al. Mutations in SLC34A3/NPT2c are associated with kidney stones and nephrocalcinosis. J Am Soc Nephrol2014;25(10):2366–2375. doi: 10.1681/ASN.2013101085
6. Wagner CA, Rubio-Aliaga I, Hernando N. Renal phosphate handling and inherited disorders of phosphate reabsorption: an update. Pediatr Nephrol2019;34(4):549–559. doi: 10.1007/s00467-017-3873-3
7. Colazo JM, Reasoner SA, Holt G, Faugere MCM, Dahir KM. Hereditary Hypophosphatemic Rickets with Hypercalciuria (HHRH) Presenting with Genu Valgum Deformity: Treatment with Phosphate Supplementation and Surgical Correction. Case Rep Endocrinol 2020 9; 2020:1047327. doi: 10.1155/2020/1047327
8. Tieder M, Modai D, Samuel R, Arie R et al. Hereditary hypophosphatemic rickets with hypercalciuria. N Engl J Med 1985 7; 312 (10): 611–617. doi: 10.1056/NEJM198503073 121003
9. Savenkova ND, Leviashvili ZhG. Tubulopathy with the leading rickets syndrome: hypophosphatemic rickets in children B: N.D. Savenkova ed. Hereditary kidney disease in children. Levsha. SPb (Saint-Petersburg). 2020; 207–223 (In Russ.)
10. Chen A, Ro H, Mundra VRR, Joseph K et al. Description of 5 Novel SLC34A3/NPT2c Mutations Causing Hereditary Hypophosphatemic Rickets With Hypercalciuria. Kidney Int Rep.2019 17; 4(8):1179–1186. doi: 10.1016/j.ekir.2019.05.004
11. Tang AR, Hinz LE, Khan A, Kline GA. Phosphate matters when investigating hypercalcemia: a mutation in SLC34A3 causing HHRH. Endocrinol Diabetes Metab Case Rep 2019 26; 2019(1):1–6. doi: 10.1530/EDM-19-0058
12. Ichikawa S, Tuchman S, Padgett LR, Gray AK et al. Intronic deletions in the SLC34A3 gene: a cautionary tale for mutation analysis of hereditary hypophosphatemic rickets with hypercalciuria. Bone2014; 59:53–56. doi: 10.1016/j.bone.2013.10.018.
13. Leviashvili ZhG. Tubulopathy with the leading rickets syndrome: hypophosphatemic rickets in children B: N.D. Savenkova ed. Hereditary kidney disease in children. Levsha. SPb (SaintPetersburg). 2020; 90–133 (In Russ.)
14. Liu L, Gao X, Ma Y, Jia S et al. [Clinical feature and variant analysis of a case with hereditary hypophosphatemic rickets with hypercalciuria]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi2020 10; 37 (6):637–640. Chinese.doi: 10.3760/cma.j.issn.1003-9406.2020.06.010.
15. Dreimane D, Chen A, Bergwitz C. Ther Description of a novel SLC34A3.c.671delT mutation causing hereditary hypophosphatemic rickets with hypercalciuria in two adolescent boys and response to recombinant human growth hormone. Ther Adv Musculoskelet Dis2020 12;12:1759720X20912862. doi: 10.1177/1759720X20912862
16. Rafaelsen S, Johansson S, Ræder H, Bjerknes R. Hereditary hypophosphatemia in Norway: a retrospective population-based study of genotypes, phenotypes, and treatment complications. Eur J Endocrinol2016; 174(2):125–36. doi: 10.1530/EJE-15-0515
17. Shimada T, Hasegawa H, Yamazaki Y, Muto T et al. FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis. J Bone Miner Res2004;19(3):429–435. doi: 10.1359/JBMR.0301264
18. Phulwani P, Bergwitz C, Jaureguiberry G, Rasoulpour M, Estrada E. Hereditary hypophosphatemic rickets with hypercalciuria and nephrolithiasis-identification of a novel SLC34A3/NaPi-IIc mutation. Am J Med Genet A2011;155A(3):626–633. doi: 10.1002/ajmg.a.33832
19. Pesta DH, Tsirigotis DN, Befroy DE, Caballero D et al. Hypophosphatemia promotes lower rates of muscle ATP synthesis. FASEB J2016;30(10):3378–3387. doi: 10.1096/fj.201600473R
20. Papizh SV, Bashirova ZR. Hereditary hypophosphatemic rickets with hypercalciuria (case report). Nephrology (Saint-Petersburg). 2018; 22(2):88–96 (In Russ.). https://doi.org/10.24884/1561-6274-2018-22-2-88-96
21. Acar S, BinEssa HA, Demir K, Al-Rijjal RA et al. Clinical and genetic characteristics of 15 families with hereditary hypophosphatemia: Novel Mutations in PHEX and SLC34A3. PLoS One2018 5;13(3):e0193388. doi: 10.1371/journal.pone.0193388
22. Gohil A, Imel EA. FGF23 and Associated Disorders of Phosphate Wasting. Pediatr Endocrinol Rev 2019;17(1):17–34
23. Taguchi K, Yasui T, Milliner DS, Hoppe B, Chi T. Genetic Risk Factors for Idiopathic Urolithiasis: A Systematic Review of the Literature and Causal Network Analysis. Eur Urol Focus 2017;3(1):72–81. doi: 10.1016/j.euf.2017.04.010
24. Arcidiacono T, Mingione A, Macrina L, Pivari F et al. Idiopathic calcium nephrolithiasis: a review of pathogenic mechanisms in the light of genetic studies. Am J Nephrol2014;40(6):499–506. doi: 10.1159/000369833
25. Rodriguez Cuellar CI, Wang PZT, Freundlich M, Filler G. Educational review: role of the pediatric nephrologists in the work-up and management of kidney stones. Pediatr Nephrol 2020;35(3):383–397. doi: 10.1007/s00467-018-4179-9
26. Papizh S.V. Hypercalcemia in children. Nephrology(SaintPetersburg) 2020;24(2):42–51 (In Russ.). doi.org/10.36485/1561-6274-2020-24-2-42-51
27. Leviashvili ZHG, Savenkova ND. Spravochnik po nasledstvennym sindromam s patologiej pochek u detej. Levsha, SPb, 2015. www.levshaprint.ru s 104
28. Walton RJ, Bijvoet OL. Nomogram for derivation of renal threshold phosphate concentration. Lancet1975; 16: 2(7929):309–310. doi: 10.1016/s0140-6736(75)92736-1
29. Leviashvili ZHG, Savenkova ND, Musaeva AV, Belov DYu. Indicators of inorganic phosphate, blood parathyroid hormone and renal tubular phosphate reabsorption in children with hereditary hypophosphatemic rickets. Nephrology(Saint-Petersburg) 2014; (18) 3: 45–56 (In Russ.)
30. Haito-Sugino S, Ito M, Ohi A, Shiozaki Y et al. Processing and stability of type IIc sodium-dependent phosphate cotransporter mutations in patients with hereditary hypophosphatemic rickets with hypercalciuria. Am J Physiol Cell Physiol2012 1;302(9):C1316–1330. doi: 10.1152/ajpcell.00314.2011
31. Dhir G, Li D, Hakonarson H, Levine MA. Late-onset hereditary hypophosphatemic rickets with hypercalciuria (HHRH) due to mutation of SLC34A3/NPT2c. Bone2017; 97:15–19. doi: 10.1016/j.bone.2016.12.001
32. Daga A, Majmundar AJ, Braun DA, Gee HY et al. Whole exome sequencing frequently detects a monogenic cause in early onset nephrolithiasis and nephrocalcinosis. Kidney Int 2018;93(1):204–213. doi: 10.1016/j.kint.2017.06.025
33. Chi Y, Zhao Z, He X, Sun Y et al. A compound heterozygous mutation in SLC34A3 causes hereditary hypophosphatemic rickets with hypercalciuria in a Chinese patient. Bone2014;59:114–121. doi: 10.1016/j.bone.2013.11.008
Review
For citations:
Leviashvili Zh.G., Savenkova N.D., Lyubimova O.V., Levi N.L., Amiryan M.О., Karpova T.V. Orphanic hereditary hypophosphatemic rachit with hypercalciuria, nephrocalcinosis on account of mutation gene SLC34A3(Review and case report). Nephrology (Saint-Petersburg). 2021;25(3):52-60. (In Russ.) https://doi.org/10.36485/1561-6274-2021-25-3-52-60
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