17 Alpha-hydroxylase Deficiency: A Case Of Two Siblings With 46,XX And 46,XY Karyotypes
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Abstract
Background:
17α-hydroxylase deficiency (17α-OHD) is an uncommon autosomal recessive disorder and a rare variant of congenital adrenal hyperplasia (CAH). It results from CYP17A1 mutations leading to impaired cortisol and sex steroid synthesis with consequent compensatory elevations in ACTH and gonadotropins. Patients typically present with hypertension, hypokalemia, primary amenorrhea, sexual infantilism or disorders of sex development (DSD). We describe two siblings who exhibited distinct phenotypes despite sharing the same underlying condition.
Case Report:
Case 1 was a 36-year-old woman (46,XX) presenting with primary amenorrhea and long-standing hypertension. Clinical assessment revealed presence of partially developed breasts, infantile genitalia and presence of bilateral adrenal hyperplasia. Hormonal studies showed adrenal insufficiency, hypergonadotropic hypogonadism, markedly elevated DOC, and reduced 17-hydroxylated steroids. Treatment with hydrocortisone, estrogen–progesterone replacement, antihypertensives, and osteoporosis therapy resulted in complete pubertal maturation and regular menses. Case 2, her sibling (46,XY) was evaluated at age of 15 years for delayed puberty. The patient had female gender identity and phenotype despite 46,XY karyotype. She was found to have female external genitalia absent Müllerian structures, adrenal insufficiency and biochemical features that were consistent with 17α-OHD. An exploratory surgery was done which identified bilateral intra-abdominal testes. Hydrocortisone, estrogen therapy, and anti-osteoporotic measures were initiated, followed by vaginoplasty and gonadectomy.
Conclusion:
These cases highlight the importance of knowing phenotypic variability of 17α-OHD in both 46,XX and 46,XY individuals. The diagnosis of 17α-OHD should be considered not only in adolescents with delayed puberty but also in adults. Early recognition enables timely treatment thereby reducing complications such as hypertension and osteoporosis and is associated with improved quality of life.