Rickets: it’s not just vitamin D deficiency

Malnutrition of vitamin D and calcium is still the most common cause of rickets and especially in individuals with dark complexions. The capacity of the two renal enzymes in vitamin D metabolism is rather low. Only approximately 10% of 25-hydroxyvitamin D is 24-hydroxylated and 0.3% is 1α-hydroxylated. The activities of these two enzymes are reciprocally controlled by 1,25-dihydroxyvitamin D itself, and vitamin A antagonizes the action of vitamin D. Mutations in the 25-hydroxyvitamin D-1α-hydroxylase gene cause hereditary vitamin D–dependent rickets type I (VDDRI). The domains that are essential for the enzyme activity were identified and are rather selective. X-linked hypophosphatemic rickets is caused by mutations in the PHEX gene and inactivity of the membrane-bound endopeptidase, resulting in impairment of both Na-dependent P-cotransporter and vitamin D metabolism. Likewise, tumor-induced osteomalacia is related to overproduction by a mesenchymal tumor of the putative phosphatonin with remission after resection of the tumor. These disease mechanisms lead to a rational algorithmic approach to diagnosis of rickets.