Cytochrome P450 oxidoreductase deficiency (Cytochrome P450 oxidoreductase deficiency) - Gen POR.

The cytochrome P450 oxidoreductase deficiency is altered hormone production, which specifically affects steroid hormones. Hormonal changes associated with cytochrome P450 oxidoreductase deficiency can affect the development of the reproductive system, skeleton and other body parts. These signs and symptoms are usually present at birth or become manifest in early childhood.

Signs and symptoms of this disease vary from mild to severe. Signs and symptoms of mild cases may include primary amenorrhea, infertility in men and women, and polycystic ovary syndrome (PCOS). People with mild cases of cytochrome P450 oxidoreductase deficiency can have ambiguous genitalia and infertility. These individuals usually have no skeletal abnormalities.

Meanwhile, the severe form of the disease is often called Antley-Bixler syndrome with genital abnormalities and impaired steroidogenesis. Hormonal changes in men and women affected lead to the development of ambiguous genitalia or other genital abnormalities and infertility. Severe cases are also characterized by skeletal abnormalities, particularly involving the bones of the head and face. These include craniosynostosis, one half of the flat face and prominent forehead set ears. Other skeletal abnormalities may include contractures that limit movement, arachnodactyly, thigh bones and radiohumeral sinostosis inclined. In addition, individuals with the severe form of the disease may have choanal atresia, mental retardation and developmental delay. Some pregnant women with fetuses affected by cytochrome P450 oxidoreductase deficiency mild symptoms even though they themselves do not have the disease. These women may develop hirsutism, acne and a deep voice. These changes disappear shortly after birth.

This process is due to mutations per gene, located on the long arm of chromosome 7 (7q11.2). This gene encodes cytochrome P450 enzyme oxidoreductase. This enzyme is required for normal functioning of over 50 enzymes in the cytochrome P450 family. The cytochrome P450 enzymes are involved in the synthesis and metabolism of various chemicals and molecules inside cells. These enzymes are critical for the synthesis of cholesterol and steroid hormones. Moreover, cytochrome P450 enzymes are involved in the metabolism of ingested substances such as drugs in the liver. Because cytochrome P450 oxidoreductase helps regulate the activity of these enzymes, it is believed that variations in the per gene can influence the drug metabolism in individuals affected.

There are more than 50 mutations in the gene accountable for cytochrome P450 oxidoreductase deficiency. Most mutations change the amino acids in cytochrome P450 oxidoreductase. These mutations per gene significantly reduce the activity of the enzyme, which cuts the production of steroid hormones. Changes in sex hormones such as testosterone and estrogen lead to problems with sexual development. Reducing the activity of cytochrome P450 oxidoreductase can also disrupt the production of cholesterol, which probably affects normal bone formation in severe cases of the disease. It is likely that a molecule called retinoic acid also plays a role in skeletal abnormalities found in severe cases, because decomposition of retinoic acid oxidoreductase requires cytochrome P450. If a deficiency of P450 oxidoreductase prevents cytochrome retinoic acid decomposes, the resulting excess of that molecule can stimulate abnormal growth and bone fusion.

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 cytochrome P450 oxidoreductase deficiency, by complete PCR amplification of exons per 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).