Abstract
Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare genetic condition with autosomal recessive inheritance and a prevalence of 1 in 250000. It is due to mutation of the SLC4A3 gene. Correct diagnosis of this condition is important as treatment with active vitamin D metabolites is contraindicated. Evolution of the disease despite initial completely normal biochemistry has been observed, potentially creating diagnostic confusion. The first child presented at the age of 5.5 years with features of rickets. He had an abnormal bone profile with normal vitamin D levels. Urinary phosphate studies were compatible with HHRH. He was treated with phosphate supplementation and potassium citrate. He has well responded well to treatment. The second child initially presented at 1.5 years of age with leg bowing and a family history of hypercalciuria. All investigation findings, including urinary phosphate studies, were within normal limits. At the age of 2.5 years, he again presented with worsening of bowing. Biochemical and urinary investigations were repeated and laboratory findings were now compatible with HHRH. These cases highlight the importance of repeated investigations despite initial normal parameters, if the initial clinical suspicion is strong. Clinical- and investigation-based diagnosis of this rare genetic disease, HHRH, is feasible in resource limited setting.
Keywords: Hereditary hypophosphatemic rickets with hypercalciuria, evolution of investigation findings, clinical diagnosis of the disease
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References
Bergwitz C, Roslin NM, Tieder M, Loredo-Osti JC, Bastepe M, Abu-Zahra H, Frappier D, Burkett K, Carpenter TO, Anderson D, Garabedian M, Sermet I, Fujiwara TM, Morgan K, Tenenhouse HS, Juppner H. 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;78:179-192.Epub 2005 Dec 9
Bergwitz C, Miyamoto KI. Hereditary hypophosphatemic rickets with hypercalciuria: pathophysiology, clinical presentation, diagnosis and therapy. Pflugers Arch. 2019;471:149-163. Epub 2018 Aug 14
Zhu Z, Bo-Ran Ho B, Chen A, Amrhein J, Apetrei A, Carpenter TO, Lazaretti-Castro M, Colazo JM, McCrystal Dahir K, Geßner M, Gurevich E, Heier CA, Simmons JH, Hunley TE, Hoppe B, Jacobsen C, Kouri A, Ma N, Majumdar S, Molin A, Nokoff N, Ott SM, Peña HG, Santos F, Tebben P, Topor LS, Deng Y, Bergwitz C. An update on clinical presentation and responses to therapy of patients with hereditary hypophosphatemic rickets with hypercalciuria (HHRH). Kidney Int. 2024;105:1058-1076. Epub 2024 Feb 15. Erratum in: Kidney Int. 2024;106:159.
Tieder M, Modai D, Shaked U, Samuel R, Arie R, Halabe A, Maor J, Weissgarten J, Averbukh Z, Cohen N, Edelstein S, Liberman UA. “Idiopathic” hypercalciuria and hereditary hypophosphatemic rickets. Two phenotypical expressions of a common genetic defect. N Engl J Med. 1987;316:125-129.
Bose A, Bushinsky DA. Nephrolithiasis, nephrocalcinosis, and hypercalciuria. In: Kimmel PL, Rosenberg ME, editors. Chronic Renal Disease. 2nd ed. San Diego: Academic Press; 2020. p. 1117-1140.
Chi Y, Zhao Z, He X, Sun Y, Jiang Y, Li M, Wang O, Xing X, Sun AY, Zhou X, Meng X, Xia W. A compound heterozygous mutation in SLC34A3 causes hereditary hypophosphatemic rickets with hypercalciuria in a Chinese patient. Bone. 2014;59:114-121. Epub 2013 Nov 16
Hanna C, Potretzke TA, Chedid M, Rangel LJ, Arroyo J, Zubidat D, Tebben PJ, Cogal AG, Torres VE, Harris PC, Sas DJ, Lieske JC, Milliner DS, Chebib FT. Kidney cysts in hypophosphatemic rickets with hypercalciuria: a case series. Kidney Med. 2022;4:100419.
Walker E, Hayes W, Bockenhauer D. Inherited non-FGF23-mediated phosphaturic disorders: a kidney-centric review. Best Pract Res Clin Endocrinol Metab. 2024;38:101843. Epub 2023 Nov 25
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;2020:1047327.
Karakilic-Ozturan E, Ozturk AP, Oney C, Kardelen Al AD, Yildirim ZY, Balci HI, Poyrazoglu S, Bas F, Darendeliler F. SLC34A3 gene mutation as a rare cause of hypophosphatemia in two siblings. Acta Endocrinol (Buchar). 2022;18:387-391.
