A case of 17 alpha-hydroxylase deficiency

Abstract

17α-hydroxylase and 17,20-lyase are enzymes encoded by the CYP17A1 gene and are required for the synthesis of sex steroids and cortisol. In 17α-hydroxylase deficiency, there are low blood levels of estrogens, androgens, and cortisol, and resultant compensatory increases in adrenocorticotrophic hormone that stimulate the production of 11-deoxycorticosterone and corticosterone. In turn, the excessive levels of mineralocorticoids lead to volume expansion and hypertension. Females with 17α-hydroxylase deficiency are characterized by primary amenorrhea and delayed puberty, with accompanying hypertension. Affected males usually have female external genitalia, a blind vagina, and intra-abdominal testes. The treatment of this disorder is centered on glucocorticoid and sex steroid replacement. In patients with 17α-hydroxylase deficiency who are being raised as females, estrogen should be supplemented, while genetically female patients with a uterus should also receive progesterone supplementation. Here, we report a case of a 21-year-old female with 17α-hydroxylase deficiency who had received inadequate treatment for a prolonged period of time. We also include a brief review of the recent literature on this disorder.

A Novel Missense Mutation in the CLPP Gene Causing Perrault Syndrome Type 3 in a Turkish Family

“…Autoimmunity is also considered as one of the important exclusion factors in patients with ovarian insufficiency, especially in secondary amenorrhea cases (21,22). Congenital disorders of adrenal and gonadal steroidogenesis are also rare causes of ovarian failure (23). Similarly, hearing loss is reported to be present in approximately 50% of women with Turner syndrome (18).…”

Current views on the diagnosis and management of hypokalaemia in children

“…The patients suffering from apparent mineralocorticoid excess have an enzymatic defect caused by mutations in the 11‐beta‐hydroxysteroid dehydrogenase type 2 gene encoding for the enzyme 11‐beta‐hydroxysteroid dehydrogenase type 2, which inactivates cortisol to cortisone. Thus, this defect leads to inappropriate mineralocorticoid activity of cortisol . Clinical features of this syndrome include severe hypertension in early childhood, low potassium levels, low birthweight and growth failure.…”

“…Male patients have ambiguous genitalia of variable severity and may be undiagnosed until adolescence, having been raised as girls as the first sign of the disease is a primary amenorrhoea. 46 patients may have delayed puberty, lack of menses, hypertension and the absence of other secondary sexual maturation signs . This syndrome should be considered in patients with sexual differentiation or maturation impairment along with hypertension and/or hypokalaemia.…”

DDIEM: Drug Database for Inborn Errors of Metabolism

“…Hydrocortisone as a replacement therapy for patients with 17alpha-hydroxylase deficiency (OMIM:202110) [40]. Functional complementation of a genetically defective protein by stimulation Sodium valproate activates the expression of one glycogen phosphorylase isoform, GP-BB, which in turn results in a decrease in intracellular glycogen accumulation, a dominant feature of glycogen storage disease type V (OMIM:232600) [41].…”