The disease manifests within the first year of life with hypotonia, tetany, seizures, muscle weakness, and poor growth. Progressively, patients present with rachitic deformities (bowed legs, rachitic rosary...). Enamel hypoplasia is occasionally observed.
The disease is due to inactivating mutations in the CYP27B1 gene (12q14) that codes for 1-alpha-hydroxylase which converts the vitamin D precursor calcidiol to calcitriol, the vitamin D active metabolite. This defect in the synthesis of vitamin D leads to defective intestinal absorption of calcium and phosphate.
