Isolated 17,20-lyase deficiency

Autosomal recessive - en

Isolated 17,20-lyase deficiency is a rare congenital disorder that affects the production of sex steroids due to a defect in the enzyme 17,20-lyase. This enzyme is crucial for the biosynthesis of androgens and estrogens from progestogens.

Pathophysiology

The enzyme 17,20-lyase, also known as CYP17A1, is responsible for the conversion of pregnenolone and progesterone into their respective 17-hydroxylated products, which are then converted into dehydroepiandrosterone (DHEA) and androstenedione. In isolated 17,20-lyase deficiency, mutations in the CYP17A1 gene impair this conversion, leading to decreased levels of DHEA and androstenedione, and consequently, reduced synthesis of testosterone and estradiol.

Clinical Presentation

Patients with isolated 17,20-lyase deficiency typically present with ambiguous genitalia or disorder of sex development (DSD) in 46,XY individuals, due to insufficient androgen production. 46,XX individuals may present with delayed puberty, primary amenorrhea, and lack of secondary sexual characteristics.

Diagnosis

Diagnosis is based on clinical presentation, hormonal assays showing low levels of androgens and estrogens with elevated levels of gonadotropins, and genetic testing confirming mutations in the CYP17A1 gene.

Treatment

Management of isolated 17,20-lyase deficiency involves hormone replacement therapy to induce and maintain secondary sexual characteristics and to address any associated adrenal insufficiency. Glucocorticoids may be administered to suppress elevated adrenocorticotropic hormone (ACTH) levels.

Related Pages

• Congenital adrenal hyperplasia
• Disorder of sex development
• CYP17A1
• Androgen
• Estrogen
• Hormone replacement therapy

See Also

• Endocrinology
• Genetic disorder
• Steroidogenesis