Steroid 5 alpha-reductase 2 deficiency: virilization in early infancy may be due to partial function of mutant enzyme

Male pseudohermaphroditism due to steroid 5 alpha-reductase deficiency is the consequence of mutations in the gene encoding the type 2 isoenzyme. Most (60%) affected subjects have homozygous mutations, and the remainder are compound heterozygotes or presumed compound heterozygotes. We report an Italian subject with phenotypic and endocrine features of 5 alpha-reductase 2 deficiency who is homozygous for a substitution mutation (H231R). Although close consanguinity is not present, genealogical data demonstrated that the parents are distantly related, and both parents and the maternal grandmother are heterozygous carriers of the mutation. The fact that this particular mutation results in the formation of an enzyme with considerable residual activity may explain in part the significant degree of virilization that took place in this subject in early infancy. This same mutation (H231R) is present in heterozygous form in two other families, an African-American family and an American family of northern European descent.