Late-onset 21-hydroxylase deficiency is an allelic variant of congenital adrenal hyperplasia characterized by attenuated clinical expression and different HLA haplotype associations.
Three families with late-onset 21-hydroxylase deficiency were studied. Homozygous females presented with symptoms of mild hyperandrogenism such as acne, hirsutism, oligomenorrhea and menometrorrhagia. A homozygous male was asymptomatic and had reached normal adult height. The diagnosis of 21-hydroxylase deficiency was based upon markedly elevated responses of plasma 17-hydroxyprogesterone during a short (30-min) ACTH infusion test. The propositi of two of the families were diagnosed despite long-standing glucocorticoid therapy and adrenal suppression by using a prolonged (48-hour) ACTH infusion. Heterozygotes of late-onset 21-hydroxylase deficiency had mildly elevated 17-hydroxy-progesterone responses to ACTH. Late-onset 21-hydroxylase deficiency was inherited as an autosomal recessive trait with close linkage to the histocompatibility leukocyte antigens. The B14 haplotype was present in all affected members. One affected female had a daughter with classic, salt-losing 21-hydroxylase deficiency. Mixed heterozygosity of this patient for a classic and a late-onset 21-hydroxylase deficiency allele may have caused the classic phenotype in her daughter (homozygote for 2 classic alleles).
D000312:Adrenal Hyperplasia, Congenital / Q000235:genetics* / Q000276:immunology; D000324:Adrenocorticotropic Hormone; D000328:Adult; D005260:Female; D006680:HLA Antigens / Q000032:analysis*; D006801:Humans; D006908:Hydroxyprogesterones / Q000097:blood; D008297:Male; D010375:Pedigree; D013250:Steroid Hydroxylases / Q000172:deficiency*
D006680:HLA Antigens; D006908:Hydroxyprogesterones; D000324:Adrenocorticotropic Hormone; D013250:Steroid Hydroxylases