A case of vitamin d-dependent rickets type 1a with a novel mutation in the uzbek population

Vitamin d-dependent rickets type 1a (vddr-1a) (online mendelian inheritance in man #264700) is a rare,autosomal recessively inherited disorder due to inactivating mutations in cyp27b1. it is characterized by early onset of rickets with hypocalcemia. we aimed to describe the clinical and laboratory findings in a vddr-1a case and to report a novel homozygote truncating mutation nm_000785.3 c.403c>t (p.q135*) in cyp27b1 which to our knowledge is the first described mutation in the uzbek population. the patient was admitted with tetany at the age of 12 months. he was a healthy uzbek boy until 9 months of age when he had a seizure due to hypocalcemia. vitamin d treatment was given orally in turkmenistan (no data available for dose and duration). the patient was the product of a consanguineous marriage. his brother had died with hypocalcemia and pneumonia. at physical examination,anthropometric measurements were within normal limits; he had caput quadratum,enlarged wrists,and carpopedal spasm. blood calcium,phosphorus,alkaline phosphatase,and parathormone (pth) levels were 5.9 mg/dl,3.5 mg/dl,987 iu/l,and 182.8 pg/ml (12-72),respectively. radiological findings included cupping and fraying of the radial and ulnar metaphyses. renal ultrasound revealed nephrocalcinosis (grade 1). despite high serum pth and 25-hydroxyvitamin d3 levels,1,25-dihydroxyvitamin d3 level was low,suggesting a diagnosis of vddr-1a. the patient was treated with calcium carbonate and calcitriol. dna sequencing revealed a novel homozygous mutation of nm_000785.3 c.403c>t (p.q135*) in cyp27b1. vddr-1a is a rare disorder which needs to be considered even in countries where nutritional vitamin d deficiency is still common. © journal of clinical research in pediatric endocrinology.