title: A Case of Vitamin D-Dependent Rickets Type 1A with a Novel Mutation in the Uzbek Population.
abstract: 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.
authors.forename: Bahar
authors.initials: B
authors.lastname: Özcabı
authors.forename: Feride
authors.initials: F
authors.lastname: Tahmiscioğlu Bucak
authors.forename: Sevinç
authors.initials: S
authors.lastname: Jaferova
authors.forename: Çiğdem
authors.initials: Ç
authors.lastname: Oruç
authors.forename: Amra
authors.initials: A
authors.lastname: Adrovic
authors.forename: Serdar
authors.initials: S
authors.lastname: Ceylaner
authors.forename: Oya
authors.initials: O
authors.lastname: Ercan
authors.affiliation: İstanbul University Cerrahpaşa Faculty of Medicine, Department of Pediatric Endocrinology, İstanbul, Turkey, E-mail: olcayevliyaoglu@hotmail.com.
authors.forename: Olcay
authors.initials: O
authors.lastname: Evliyaoğlu
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics*; D002117:Calcitriol / Q000627:therapeutic use; D002119:Calcium Carbonate / Q000627:therapeutic use; D003241:Consanguinity; D053098:Familial Hypophosphatemic Rickets / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D010290:Parents; D014610:Uzbekistan; D014815:Vitamins / Q000627:therapeutic use
chemical_list: D014815:Vitamins; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; C000600378:CYP27B1 protein, human; D002117:Calcitriol; D002119:Calcium Carbonate