HLA linkage and B14, DR1, BfS haplotype association with the genes for late onset and cryptic 21-hydroxylase deficiency

Classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21-OH-def) has been established to be an HLA-linked, recessive monogenetic disease. However, two nonclassical forms of 21-OH-def have also been described: 'cryptic' 21-OH-def, which has been shown to be HLA-linked, and 'late onset' 21-OH-def, for which the status of linkage to HLA has been less certain. The authors now describe studies of 8 additional unrelated probands with symptomatic, 'late-onset' 21-OH-def, and conclude that this form is also HLA-linked. Both 'late onset' and 'cryptic' 21-OH-def are highly associated with the same HLA antigens and markers (HLA-B14, HLA-DR1, and Bf type S) in individuals from different ethnic and geographical backgrounds. Since both 'late onset' and 'cryptic' 21-OH-def appear to occur in individuals with one classical 21-OH-def [21-OH(CAH)] allele who in addition have another 21-OH-def allele, as well as in individuals who appear to be homozygous for variant 21-OH-def alleles, and since both late onset and cryptic 21-OH-def appear to occur in the same families, the data suggest that these syndromes may represent different clinical expressions of similar or identical nonclassical 21-OH-def alleles.