17-α-Hydroxylase Deficiency Due to P.R362C Mutation in two Sisters From India

ABSTRACT Objective: 17-α-Hydroxylase deficiency (17-OHD) is a very rare disorder of adrenal and gonadal steroidogeneis. The patient usually presents as a phenotypic female with hypertension, hypokalemia, and delayed puberty due to hypergonadotropic hypogonadism. Karyotype may be 46,XX or 46,XY. Timely diagnosis leads to effective management of the patient and appropriate screening of family members. Methods: Case report and review of the literature. Results: A 24-year-old woman presented with primary amenorrhea and poor development of secondary sexual characters along with persistent hypokalemia and hypertension of several years duration. Examination did not show any stigma of Turner syndrome, features of any pituitary hormone deficiency, or hypothyroidism. Further evaluation revealed hypergonadotropic hypogonadism with persistent hypokalemia and refractory hypertension. The karyotype was 46,XX. Possible diagnosis of 17-OHD was considered, which was supported by low serum cortisol, high adrenocorticotropic hormone, and very high serum progesterone level and suppressed plasma renin activity. The patient had a younger sister (11 years old) whom we called for evaluation. She was found to have diffuse skin and mucosal hyperpigmentation along with hypertension. Analysis of the CYP17A1 gene of these two patients revealed a homozygous mutation, p.R362C (c.1084C>T), which has been shown to completely abolish the activity of both 17-α-hydroxylase and 17,20-lyase. Conclusion: The p.R362C (c.1084C>T) mutation led to 17-OHD in two sisters. One sister was diagnosed as a result of family screening. This is the first report of this mutation in India. Abbreviations: 17-OHD 17-α-hydroxylase deficiency; ACTH adrenocorticotropic hormone; CYP17A1 cytochrome P450 17-α-1; PRA plasma renin activity