Author:
Mejia-Gaviria Natalia,Gil-Peña Helena,Coto Eliecer,Pérez-Menéndez Teresa M,Santos Fernando
Abstract
Abstract
Hereditary hypophosphatemic rickets with hypercalciuria is a rare autosomal recessive disorder (OMIM #241530), characterized by decreased renal phosphate reabsorption that leads to hypophosphatemia, rickets, and bone pain; hypophosphatemia is believed to stimulate 1,25 dihydroxyvitamin D synthesis which, in turn, results in hypercalciuria. Hereditary hypophosphatemic rickets with hypercalciuria is caused by loss-of-function in the type 2c sodium phosphate cotransporter encoded by the SLC34A3 gene. This report shows a family with a non-previously identified mutation in the SLC34A3 gene and exhibiting mild and different manifestations of HHRH. The probandus had hypophosphatemia, elevated serum 1,25 dihydroxyvitamin D concentrations, high serum alkaline phosphatase levels, hypercalciuria and nephrocalcinosis. The other members of the family presented some of these alterations: the mother, hypercalciuria and high 1,25 dihydroxyvitamin D concentrations; the son, hypercalciuria, high 1,25 dihydroxyvitamin D values and elevated alkaline phosphatases; the father, high alkaline phosphatases. The genetic analysis revealed the existence of a single mutation (G78R) in heterozygosis in the SLC34A3 gene in the probandus, her mother and her brother, but not in the father. These findings suggest that he mutation in heterozygosis likely gave rise to a mild phenotype with different penetrance in the three relatives and also indicates that the elevation of 1,25 dihydroxyvitamin D does not result from hypophosphatemia. Thus, this family raises some issues on the transmission and pathophysiology of hereditary hypophosphatemic rickets with hypercalciuria.
Publisher
Springer Science and Business Media LLC
Subject
Pharmacology (medical),Genetics(clinical),General Medicine
Reference16 articles.
1. Tieder M, Modai D, Samuel R, Arie R, Halabe A, Bab I, Gabizon D, Liberman UA: Hereditary hypophosphatemic rickets with hypercalciuria. N Engl J Med. 1985, 312: 611-617. 10.1056/NEJM198503073121003.
2. Royer P, Mathieu H, Gerbeaux S, Frederich A, Rodriguez-Soriano J, Dartois AM, Cuisinier P: Idiopathic hypercalciuria with nanism and renal involvement in children. Ann Pediatr (Paris). 1962, 9: 147-163.
3. 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. 10.1086/499409.
4. Segawa H, Kaneko I, Takahashi A, Kuwahata M, Ito M, Ohkido I, Tatsumi S, Miyamoto K: Growth-related renal type II Na/Pi cotransporter. J Biol Chem. 2002, 277: 19665-19672. 10.1074/jbc.M200943200.
5. Foster IC, Hernando N, Biber J, Murer H: Proximal tubular handling of phosphate: A molecular perspective. Kidney Int. 2006, 70: 1548-1559. 10.1038/sj.ki.5001813.
Cited by
41 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献