Bone Abstracts

Objectives: Vitamin D dependent rickets type I (VDDR-I) is an autosomal recessive disorder with impaired activation of vitamin D, caused by mutations in CYP27B1. Characteristic clinical features are hypotonia, muscle weakness, growth failure, hypocalcemic seizures in early infancy, and radiographic findings of rickets. We aimed to describe the clinical and laboratory findings in a VDDR-1 case and to report a mutation in CYP27B1.

Methods and results: The patient was admitted with seizure at the age of 14 months. Blood calcium, phosphorus, alkaline phosphatase, parathyroid hormone (PTH), 25(OH) vitamin D, and 1,25(OH)2 vitamin D levels were 5.1 mg/dl, 3.7 mg/dl, 705 IU/l, 429 pg/ml, 24.9 ng/ml, and 8.8 pg/ml, respectively. Radiological findings included cupping and fraying of the radial and ulnar metaphysis. On molecular genetic study, the patient revealed a compound heterozygous mutation for the 7-bp duplication 1319-1325dupCCCACCC (Phe443Profs*24) and IVS3+1 G>A in the CYP27B1 gene. Analysis of the family members showed that the asymptomatic mother and sister were heterozygous mutations for IVS3+1 G>A, and the father was heterozygous for the Phe443Profs*24. The patient was treated with calcium lactate and calcitriol.

Conclusion: Until now, five Korean patients with VDDR-I have been studied and three distinct mutations have been identified. The splice site mutation, IVS3+1 G>A, occurred in 5 of 10 alleles, the Phe443Profs*24 occurred in four alleles and the 2561G>A (W328X) mutation in exon 6 occurred only one allele. This patient showed a compound heterozygosity for IVS3+1 G>A and Phe443Profs*24 mutation. So, Korean patients with VDDR-I revealed only three different mutations in 12 alleles, suggesting that the genetic defect in the CYP27B1 gene is homogeneous in Korean ethnic group.

Disclosure: The authors declared no competing interests.