Endocrine Abstracts

Introduction: X-linked hypophosphatemic rickets is the most common form of familial hypophosphatemic rickets. It is caused by a defect in renal phosphate transport leading to phosphate wasting and hypophosphatemia. Furthermore 1,25-dihydroxyvitamin D concentrations are inappropriately normal in regard to hypophosphatemia. Clinical manifestation of the disease are skeletal deformities, short stature, osteomalacia, dental abscesses, bone pain, and loss of hearing. PHEX is located on Xp22.1 and inactivating mutations of PHEX have been identified as the gene defective in X-linked hypophosphatemic rickets.

Clinical characteristics: We report three cases of hypophosphatemic rickets. Two patients are female (55 and 24 years old), one is male (49 years old). Age at diagnosis ranged from early childhood to the age of 35 years. One patient underwent hip replacement at the age of 41 due to secondary arthritis caused by coxa vara. Two patients have mild calcification of kidney tissue. One patient suffers from loss of hearing since the age of 17. All three patients have been treated with phosphate supplements, two patients receive 1,25-dihydroxycholecalciferol for treatment of secondary hypoparathyroidism. Under this regimen blood levels of calcium, phosphate and parathyroid hormone are in normal range. In all patients at least one family member is affected by rickets, as well.

Genetical analysis: Genetic mutational analysis of the PHEX gene was performed in all patients. In both female patients known mutations were found: 683delTC (exon 6, codon 228) and c.1952G>C (exon 19, codon 651, R651P). However, in one patient and an unknown nonsense mutation was found in exon 7, codon 245 (c.735T>G, Tyr245Term, Y245X).

Conclusions: We report a novel nonsense mutation of PHEX that has not been identified so far. It underlines that genetic testing of patients and family members is needed to guarantee early diagnosis and treatment.