Subtle 17α-hydroxylase/17,20-lyase deficiency with homozygous Y201N mutation in an infertile woman

Abstract

Steroid 17α-hydroxylase deficiency is characterized by failed sexual development and mineralocorticoid hypertension. Female patients usually exhibit primary amenorrhea. Some patients with partial deficiency are reported to have menses, yet they have hypertension and hypokalemia. We describe here a normotensive, infertile female patient with menses and minimal defects in secondary sex characteristics. The patient experienced menarche at age 13, and her menstrual cycles were regular until age 18 and irregular thereafter. Pubic hair was present (Tanner stage 3), and breast maturation was within normal range (Tanner stage 5). The patient's resting blood pressure was normal, and hypokalemia was not observed despite high blood corticosterone levels and reduced plasma renin activity. Analysis of the CYP17 gene revealed that the patient was homozygous for the Y201N mutation. In vitro expression of the mutated Y201N enzyme revealed reduced activities of both 17α-hydroxylase and 17,20-lyase; however, these reductions were less than those of the F53/54DEL mutation, which also shows mild clinical deficiency of 17α-hydroxylase/ 17,20-lyase. Thus, the 17α-hydroxylase/17,20-lyaee deficiency in the present case is very mild both clinically and enzymatically. This case raises the possibility that there are infertile, menstruating women with undiagnosed 17α-hydroxylase deficiency. Copyright © 2005 by The Endocrine Society.