17β-Hydroxysteroid dehydrogenase deficiency

17β-Hydroxysteroid dehydrogenase deficiency (17β-HSD deficiency) is a rare genetic disorder affecting steroid metabolism, specifically the biosynthesis of estrogens and androgens. This condition is part of a group of disorders known as congenital adrenal hyperplasia (CAH), which involves the adrenal glands' inability to produce certain hormones properly.

Overview

17β-Hydroxysteroid dehydrogenase (17β-HSD) is an enzyme crucial for the conversion of androstenedione (a weak androgen) to testosterone (a more potent androgen), and estrone to estradiol (a more potent estrogen). Deficiency in this enzyme leads to an imbalance in the levels of androgens and estrogens, affecting sexual development and fertility.

Causes

17β-HSD deficiency is caused by mutations in the HSD17B3 gene, which provides instructions for making the enzyme. This condition is inherited in an autosomal recessive pattern, meaning both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Symptoms

The symptoms of 17β-HSD deficiency can vary widely among affected individuals. In genetic males (individuals with one X and one Y chromosome), symptoms can include ambiguous genitalia at birth, micropenis, and undescended testes. Affected individuals may also have a female-typical appearance, including a more developed breast tissue and a lack of facial hair. In genetic females (individuals with two X chromosomes), symptoms are often less apparent and may include a delayed or absent menstrual cycle and reduced fertility.

Diagnosis

Diagnosis of 17β-HSD deficiency involves a combination of physical examination, hormone level testing, and genetic testing. Hormone tests measure levels of androgens, estrogens, and other related hormones in the blood or urine. Genetic testing can confirm a diagnosis by identifying mutations in the HSD17B3 gene.

Treatment

Treatment for 17β-HSD deficiency focuses on addressing the symptoms and may include hormone replacement therapy to correct hormone imbalances. For individuals with ambiguous genitalia or other physical abnormalities, surgical options may be considered. Psychological support is also important for affected individuals and their families to address any issues related to gender identity and sexual development.

Prognosis

With appropriate medical and psychological support, individuals with 17β-HSD deficiency can lead healthy lives. Fertility may be affected, but treatments are available to assist those who wish to have children.