Congenital adrenal hyperplasia due to 3 beta-hydroxysteroid dehydrogenase deficiency

Congenital adrenal hyperplasia due to 3 beta-hydroxysteroid dehydrogenase deficiency (3β-HSD deficiency) is a rare form of Congenital adrenal hyperplasia (CAH), a group of genetic disorders that affect the adrenal glands. This condition results from mutations in the HSD3B2 gene, which encodes the enzyme 3β-hydroxysteroid dehydrogenase (3β-HSD). This enzyme is crucial for the production of all classes of adrenal steroids, including glucocorticoids, mineralocorticoids, and sex steroids. The deficiency leads to impaired steroidogenesis, affecting the synthesis of cortisol, aldosterone, and sex steroids.

Symptoms and Presentation

Individuals with 3β-HSD deficiency present a spectrum of clinical manifestations, ranging from mild to severe. The severity largely depends on the extent of enzyme deficiency. Common symptoms include salt-wasting crisis, ambiguous genitalia in genetically female infants (due to excess androgen levels), and undervirilization in genetically male infants. Other potential symptoms include failure to thrive, hypoglycemia, and hyperpigmentation.

Genetics

3β-HSD deficiency is inherited in an autosomal recessive manner. It is caused by mutations in the HSD3B2 gene, located on chromosome 1 (1p13.1). This gene provides instructions for making the enzyme involved in the biosynthesis of steroid hormones. Mutations in this gene reduce or eliminate the activity of 3β-HSD, disrupting the production of vital hormones.

Diagnosis

Diagnosis of 3β-HSD deficiency involves clinical evaluation, biochemical testing, and genetic testing. Biochemical testing can reveal elevated levels of 17-hydroxypregnenolone and dehydroepiandrosterone (DHEA), along with low levels of cortisol and aldosterone. Genetic testing can confirm mutations in the HSD3B2 gene.

Treatment

Treatment aims to replace deficient hormones and manage symptoms. Glucocorticoid replacement is used to treat cortisol deficiency and suppress adrenocorticotropic hormone (ACTH) overproduction, which drives excessive androgen production. Mineralocorticoid replacement is necessary for individuals with aldosterone deficiency to manage salt-wasting symptoms. Sex hormone management may be required for individuals with ambiguous genitalia or delayed puberty.

Prognosis

With early diagnosis and appropriate treatment, individuals with 3β-HSD deficiency can lead healthy lives. However, ongoing management is necessary to monitor hormone levels and adjust treatment as needed.

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