Aromatase deficiency ... (Aromatase deficiency) - Gen CYP19A1.

Aromatase deficiency is a disorder characterized by reduced levels of estrogen and increased testosterone levels. Women with aromatase deficiency have a typical female chromosome pattern (46, XX), but are born with ambiguous genitalia. These individuals usually have normal internal reproductive organs, but ovarian cysts develop in early childhood that disrupt ovulation. In adolescence, the women most affected do not develop secondary sexual characteristics like breast growth and menstrual periods breasts. They also tend to develop acne and hirsutism. For its part, males with this disorder have a typical male chromosome pattern (46, XY) and born with male external genitalia. Some affected males have decreased libido, abnormal sperm production, small testes and cryptorchidism.

Other signs associated with aromatase deficiency can affect both men and women, and may include overgrowth of the long bones of the arms and legs, delayed bone age, osteoporosis, hyperglycemia, excessive weight gain and fatty liver. Pregnant women with fetuses with aromatase deficiency often present with mild symptoms of the disease although they themselves do not have the disorder. These women may develop hirsutism, acne, clitoromegaly and a deep voice. These features may appear at 12 weeks of pregnancy and disappears after delivery.

This process is due to mutations in the CYP19A1 gene, located on the long arm of chromosome 15 (15q21.1). This gene encodes the enzyme aromatase. This enzyme converts androgens, which are involved in male sexual development, the different forms of estrogen. In cells, aromatase is in the endoplasmic reticulum, involved in the production, processing and transport of proteins. In women, aromatase is more active in the ovaries, which guide sexual development. In men, aromatase is active in adipose tissue. In both sexes, estrogen plays a role in the regulation of bone growth and concentrations of blood sugar. During fetal development, placental aromatase converts androgens into estrogens. This conversion in the placenta prevents androgens direct sexual development in female fetuses. After birth, the conversion of androgens to estrogens occurs in multiple tissues.

They have identified more than 20 mutations in the CYP19A1 gene in people with aromatase deficiency. These genetic changes result in a deficiency or absence of aromatase activity, resulting in an inability to convert androgens into estrogens before birth and throughout life. As a result, there is a decrease in estrogen production and increased levels of androgens, including testosterone. In women who are pregnant with an affected fetus, excess androgens in the placenta into the bloodstream of women, and can cause temporary symptoms have signs and aromatase deficiency.

This disease is inherited in an autosomal recessive pattern, that is, both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.

Tests in IVAMI: in IVAMI perform detection of mutations associated with aromatase deficiency, by complete PCR amplification of the exons of CYP19A1 gene, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).