Congenital adrenal hyperplasia due to 3β-hydroxysteroid dehydrogenase deficiency

Cortisol2

Congenital adrenal hyperplasia due to 3β-hydroxysteroid dehydrogenase deficiency (CAH due to 3β-HSD deficiency) is a rare form of congenital adrenal hyperplasia (CAH), a group of inherited disorders affecting the adrenal glands. This condition is caused by mutations in the HSD3B2 gene, which encodes the enzyme 3β-hydroxysteroid dehydrogenase (3β-HSD). This enzyme is crucial for the biosynthesis of steroid hormones, including cortisol, aldosterone, and sex steroids.

Pathophysiology

The deficiency of 3β-HSD disrupts the normal production of steroid hormones. This leads to a buildup of precursor hormones and a deficiency in the end products. The lack of cortisol can result in adrenal insufficiency, while the deficiency in aldosterone can cause salt-wasting. The imbalance in sex steroids can lead to ambiguous genitalia in affected individuals.

Clinical Presentation

The clinical manifestations of CAH due to 3β-HSD deficiency can vary widely. Common symptoms include:

• Ambiguous genitalia in newborns
• Salt-wasting crisis in infancy
• Adrenal insufficiency
• Hypotension
• Hyponatremia
• Hyperkalemia

Diagnosis

Diagnosis is typically made through a combination of clinical presentation, hormonal assays, and genetic testing. Elevated levels of 17-hydroxypregnenolone and dehydroepiandrosterone (DHEA) with low levels of cortisol and aldosterone are indicative of the disorder. Genetic testing can confirm mutations in the HSD3B2 gene.

Treatment

Management of CAH due to 3β-HSD deficiency involves hormone replacement therapy to correct the deficiencies in cortisol and aldosterone. This typically includes:

• Glucocorticoid replacement
• Mineralocorticoid replacement
• Salt supplementation

Prognosis

With appropriate treatment, individuals with CAH due to 3β-HSD deficiency can lead relatively normal lives. However, ongoing medical supervision is necessary to manage hormone levels and prevent complications.

Related Pages

• Congenital adrenal hyperplasia
• Adrenal insufficiency
• Steroid hormone
• HSD3B2