Hereditary vitamin D-resistant rickets in Greek children: genotype, phenotype, and long-term response to treatment.

We describe four patients (two pairs of children from two unrelated kindreds) from a Greek island, suffering from hereditary vitamin D-resistant rickets (HVDRR) with alopecia. There were two different homozygous mutations in the vitamin D receptor (VDR) gene of the affected members of the two kindreds that resulted in a truncated or missing receptor. The disorder began in early infancy with similar clinical, biochemical and radiological findings in all four patients, namely, alopecia (which provided the initial diagnostic evidence for HVDRR), rachitic deformities, hypocalcemia, hypophosphatemia, secondary hyperparathyroidism, and elevated serum levels of 1,25-dihydroxyvitamin D; however, the patients of kindred B had a more severe clinical expression. Treatment options include oral or intravenous calcium and active vitamin D metabolites. The response varies widely in different cases. Our patients were initially treated with high doses of 1alpha(OH)D3 and oral calcium supplementation. Kindred A patients had a satisfactory response to this regimen, while kindred B patients presented clinical and biochemical improvement when 1alpha(OH)D3 was changed to 1,25(OH)2D3. In the older patients of each kindred, treatment requirements gradually decreased during puberty, and therapy was finally discontinued before adulthood.