Cytochrome P450 oxidoreductase deficiency

A genetic disorder affecting steroid metabolism

Cytochrome P450 oxidoreductase deficiency (PORD) is a rare genetic disorder that affects the body's ability to metabolize certain steroids. This condition is caused by mutations in the POR gene, which encodes the enzyme cytochrome P450 oxidoreductase. This enzyme is crucial for the activity of all microsomal cytochrome P450 enzymes, which are involved in the synthesis and metabolism of steroids, cholesterol, and other lipids.

Pathophysiology

Cytochrome P450 oxidoreductase deficiency disrupts the normal function of cytochrome P450 enzymes, leading to impaired steroidogenesis. This can result in a variety of clinical manifestations, depending on the specific enzymes affected and the severity of the enzyme deficiency. The condition can affect the synthesis of glucocorticoids, mineralocorticoids, and sex steroids, leading to a spectrum of symptoms.

Clinical Features

The clinical presentation of PORD can vary widely. Common features include:

• Congenital adrenal hyperplasia
• Ambiguous genitalia in both males and females
• Adrenal insufficiency
• Skeletal malformations, such as craniosynostosis and limb defects
• Infertility

Genetics

Cytochrome P450 oxidoreductase deficiency is inherited in an autosomal recessive pattern. This means that an individual must inherit two copies of the mutated POR gene (one from each parent) to be affected by the disorder. Carriers, who have only one copy of the mutation, typically do not show symptoms.

Diagnosis

Diagnosis of PORD is based on clinical features, biochemical testing, and genetic analysis. Biochemical tests may show abnormal levels of steroid metabolites in the blood and urine. Genetic testing can confirm mutations in the POR gene.

Management

Management of PORD involves hormone replacement therapy to address deficiencies in steroid hormones. This may include glucocorticoids, mineralocorticoids, and sex steroids, depending on the individual's specific needs. Surgical intervention may be necessary for individuals with ambiguous genitalia or skeletal malformations.

Prognosis

The prognosis for individuals with cytochrome P450 oxidoreductase deficiency varies depending on the severity of the condition and the effectiveness of treatment. With appropriate management, many individuals can lead relatively normal lives, although some may experience ongoing health challenges.

Related pages

• Congenital adrenal hyperplasia
• Steroidogenesis
• Adrenal insufficiency
• Genetic disorders