Late-Onset Steroid 21-Hydroxylase Deficiency

Abstract

Hormonal studies and human leukocyte antigen (HLA) genotyping were performed in 5 males and 13 females who were demonstrated to have 21-hydroxylase deficiency. The enzymatic deficiency of steroidogenesis was detected by family studies of 10 females who presented with varying symptoms of androgen excess. The 10 index cases had normal genitalia at birth, but virilized to varying degrees postnatally. The additional 8 affected family members had not sought medical care, but some were found to have signs of virilization on physical exam- ination, while others were normal. Thus both late-onset (symp- tomatic) and cryptic (asymptomatic) 21-hydroxylase deficiency occurred in the same pedigree. The hormonal and genetic linkage studies indicate that the late-onset (symptomatic) form of 21- hydroxylase deficiency, like the cryptic (asymptomatic) and classical forms of 21-hydroxylase deficiency, is transmitted by an autosomal recessive gene which is linked to HLA-B. Further- more, the classical form of 21-hydroxylase deficiency associated with prenatal virilization is transmitted by an allelic variant for steroid 21-hydroxylase different from that of the nonclassical forms, late-onset (symptomatic) and cryptic (asymptomatic) 21- hydroxylase deficiency. Although these latter 2 disorders have different clinical manifestations, they demonstrate a similar de- gree of steroid 21-hydroxylase deficiency that is less severe than that observed in classical 21-hydroxylase deficiency. The hor- monal and genetic linkage data indicate that cryptic (asympto- matic) and late-onset (symptomatic) 21-hydroxylase deficiency result from the same allelic variant at the steroid 21-hydroxylase locus. A glossary of terms is presented to describe the various allelic forms of 21-hydroxylase deficiency with consistency. (J Clin Endocrinol Metab 55: 817, 1982)