Miller W L, Portale A A
Department of Pediatrics, University of California at San Francisco, Berkeley, USA.
Curr Opin Pediatr. 1999 Aug;11(4):333-9. doi: 10.1097/00008480-199908000-00012.
Dietary deficiency of vitamin D, genetic disorders of its bioactivation to 1,25-dihydroxyvitamin D [1,25(OH)2D], or disorders of vitamin D action can cause rickets. The rate-limiting, hormonally-regulated, biologically activating step in the synthesis of 1,25(OH)2D is the 1 alpha-hydroxylation of 25-hydroxyvitamin D, which occurs in kidney and other tissues and is mediated by a mitochondrial cytochrome P450 enzyme, P450c1 alpha. After many years of effort, the cDNA and gene for this enzyme were cloned in late 1997. Mutations in the P450c1 alpha gene, located on chromosome 12, cause 1 alpha-hydroxylase deficiency, also known as vitamin D-dependent rickets type I, an autosomal recessive disease characterized by rickets and impaired growth due to failure of renal synthesis of 1,25(OH)2D. X-linked hypophosphatemic rickets, a dominantly inherited disease, is caused by mutations in the PHEX gene, whose function in regulating renal phosphate and vitamin D metabolism remains to be elucidated.
维生素D的膳食缺乏、其生物活化成1,25-二羟基维生素D [1,25(OH)2D]的遗传紊乱，或维生素D作用的紊乱均可导致佝偻病。1,25(OH)2D合成过程中限速、受激素调节的生物活化步骤是25-羟基维生素D的1α-羟化，该反应发生在肾脏和其他组织中，由线粒体细胞色素P450酶P450c1α介导。经过多年努力，该酶的cDNA和基因于1997年末被克隆。位于12号染色体上的P450c1α基因突变会导致1α-羟化酶缺乏，也称为I型维生素D依赖性佝偻病，这是一种常染色体隐性疾病，其特征为佝偻病和因肾脏合成1,25(OH)2D失败而导致的生长障碍。X连锁低磷血症性佝偻病是一种显性遗传病，由PHEX基因突变引起，其在调节肾脏磷酸盐和维生素D代谢中的作用仍有待阐明。
