Background: 11β-hydroxylase deficiency (HD) represents a rare cause of congenital adrenal hyperplasia (CAH) characterized by glucocorticoid deficiency and excess of mineralcorticoids and androgens. The CYP11B1 gene on chromosome 8q22 encodes the 11β-hydroxylase.
Objective: To report clinical, biochemical and molecular features of patients with 11β-HD.
Results: Four male patients of Turkish descent with 11β-HD including two brothers were identified in our patient cohort. They were diagnosed between the ages of 1.43.3 years with tall stature (height SDS 2.585.02), increased growth velocity (SDS 1.134.83), advanced bone age (GP, 412 years), precocious pseudo-puberty (PPP) and hypertension (systolic RR >95th percentile). The sibling was diagnosed postpartum because of his family history. The plasma concentrations of 11-deoxycorticosterone (525.83091.0 ng/dl, ref. 234), of 11-desoxycortisol (14.558.0, ref. 0.020.25), testosterone (129298 ng/dl, ref. 220), and ACTH (211512 pg/ml, ref. 1050) were elevated while plasma renin activity was suppressed. Treatment with high doses hydrocortisone was required to normalize steroid metabolism (16.429 mg/m2 per day). Mutations were identified in exon 7 (c.1181insGA and c.1179_1180dupGA (p.Asn394Argfs*37) and 8 ((T→C) 5* splice site) of the CYP11B1 gene leading to an almost complete loss of function of 11β-hydroxylase. The c.1179 mutation had been described once in 1992, but not been included in the database (HGMD). The parents in each case are consanguineous and heterozygous carriers of a mutation. Testicular adrenal rest tumors (TART) developed in the two brothers. The youngest patient had sonographic sings of TART at the age of 4.
Conclusion: Tall stature with advanced bone age, PPP and hypertension may be caused by CAH due to 11β-HD, which is not detected in routine newborn screening. The therapy requires higher doses of hydrocortisone compared to those in the treatment of 21-HD. TART may be present as early as infancy or develop during the course of illness.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology