Late-Onset Steroid 21-Hydroxylase Deficiency: A Variant of Classical Congenital Adrenal Hyperplasia*

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 examination, while others were normal. Thus both late-onset (symptomatic) 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. Furthermore, 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 degree of steroid 21-hydroxylase deficiency that is less severe than that observed in classical 21-hydroxylase deficiency. The hormonal and genetic linkage data indicate that cryptic (asymptomatic) 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.

The Prevalence, Molecular Analysis and HLA Typing of Late-onset 21-Hydroxylase Deficiency in Turkish Woman with Hirsutism and Polycystic Ovary

“…Virilization was determined by the presence of masculine muscle hypertrophy or clitoromegaly and/or temporal balding. Hormonal evaluation of LOCAH was done by the level of plasma 17-hydroxyprogesterone (17-OHP) and elimination of prenatal virilization as reported previously by Kohn et al [19]. 17-OHP in blood samples were assayed by the Coat-A-Count 17-OHP procedure (a solid-phase radioimmunoassay, Diagnostic Products Corporation, Los Angeles, CA, USA).…”

Analysis of Adrenocortical Hyperplasia by Computed Tomography in Patients with Cushing's Disease, Idiopathic Hyperaldosteronism and Adrenogenital Syndrome.

“…Cases 33 and 34 had received hydrocortisone therapy for several years intermittently without benefit. The other 3 patients were diagnosed as late-onset (non-classic type) 21-hydroxylase deficiency because of moderate hirsutism and secondary amenorrhea or oligomenorrhea [15,16]. Case 38 was the father of cases 33 and 34, he had high plasma ACTH, serum DHEA and 17a-OH-progesterone but no symptoms.…”

Genotype-phenotype associations in non-classical steroid 21-hydroxylase deficiency

“…The disorder has traditionally been divided into three types according to severity of expression. (A) Salt-wasting (SW) and (B) simple virilizing (SV); the more severe SW and SV forms are collectively referred to as classical steroid 21-hydroxylase de®ciency (21-OHD), and (C) non-classical (NC21-OHD), which is associated with different degrees of postnatal virilization developing during childhood or at puberty and may be asymptomatic (1).…”