Analysis of the relation between alopecia and resistance to 1,25-dihydroxyvitamin D

Alopecia is a frequent feature in hereditary resistance to (1,25(OH)2D). We sought insight into this feature by analysing data from affected members of 30 kindreds. We assessed indices of mineral metabolism in one group with normal hair compared with a group with alopecia. Hereditary resistance to 1,25(OH)2D was diagnosed at an earlier age in alopecic patients (0.9 vs 3.3 years, P less than 0.05); this reflected late presentation of metabolic bone disease in some cases with normal hair and could not be attributed to early diagnosis resulting from the striking feature of alopecia. For untreated subjects, serum concentrations of calcium and 1,25(OH)2D were similar in both groups of patients. During calciferol therapy, however, the cases with alopecia showed lower serum calcium (1.9 vs 2.4 mmol/l, P less than 0.005), but higher serum 1,25(OH)2D (2900 v 340 pg/ml, P less than 0.005). Hair status did not predict the type of defect identified with cultured skin fibroblasts but did correlate with responsiveness of 25(OH)D 24-hydroxylase to 1,25(OH)2D3 in those cells. Cells from seven of eight kindreds with alopecia showed no 24-hydroxylase response to high doses of 1,25(OH)2D3 while cells from five of six kindreds with normal hair showed a 24-hydroxylase response to high doses of 1,25(OH)2D3. We conclude that in cases with hereditary resistance to 1,25(OH)2D alopecia reflects the more severe grades of this resistance based upon earlier age at time of diagnosis, lower potential for calcaemic response to calciferols, and lower potential for 24-hydroxylase response to 1,25(OH)2D3 by cultured skin fibroblasts.