Cytochrome P450-oxidoreductase (POR) deficiency (ORD)
Synonyms and keywords: ORD, POR deficiency, P450-oxidoreductase cytochrome deficiency

# Overview
Cytochrome P450-oxidoreductase (POR) deficiency is a type of congenital adrenal hyperplasia that caused by mutations in the flavoprotein co-factor of the enzymes CYP17A1, CYP21A2, and CYP19A1 (aromatase). Severe Undervirilization in boys and severe virilization in girls and Antley-Bixler syndrome of craniofacial malformations are clinical finding of cytocrome P450-oxidoreductase deficiency. The mainstay of therapy for cytochrome P450-oxidoreductase deficiency is hydrocortisone to replace glucocorticoid deficiency.

# Historical Perspective
In 1865, Luigi De Crecchio, an Italian pathologist was the first who discovered Congenital adrenal hyperplasia.

# Classification
There is no established classification system for cytochrome P450-oxidoreductase deficiency.

# Pathophysiology
The cytochrome P450 oxidoreductase (POR) enzyme serves as an electron donor enzyme for many enzymes such as steroid synthesis enzymes CYP17A1, and CYP21A2. Cytochrome P450-oxidoreductase deficiency is characterized by combined CYP17A1 and CYP21A2 deficiency.
- CYP17A1 encodes17-hydroxylase/17,20-hydroxylase, a cytochrome P450 enzyme which acts upon:
Pregnenolone and progesterone to add a hydroxyl (-OH) group at carbon 17 of the steroid D ring (the hydroxylase activity).
17-hydroxyprogesterone and 17-hydroxypregnenolone to split the side chain off the steroid nucleus.
- Pregnenolone and progesterone to add a hydroxyl (-OH) group at carbon 17 of the steroid D ring (the hydroxylase activity).
- 17-hydroxyprogesterone and 17-hydroxypregnenolone to split the side chain off the steroid nucleus.
- CYP21A2 encodes steroid 21-hydroxylase, a cytochrome P450 enzyme which is involved with the biosynthesis of the steroid hormones aldosterone and cortisol.
Also, cytochrome P450 oxidoreductase enzyme serves as a co-factor for an enzyme called lanosterol de-methylase (CYP51A1), which is effective in de novo cholesterol synthesis. In this disease cholesterol loss may lead to craniofacial malformations and Antley-Bixler syndrome (ABS).

# Causes
Cytochrome P450-oxidoreductase (POR) deficiency is caused by mutations in the flavoprotein that is a co-factor of the enzymes CYP17A1, CYP21A2, and CYP19A1 (aromatase).

# Differentiating  from other Diseases
Cytochrome P450-oxidoreductase deficiency must be differentiated from other diseases that cause ambiguous genitalia such as: 21-hydroxylase deficiency, 11- hydroxylase deficiency, 17 alpha-hydroxylase deficiency, and gestational hyperandrogenism.

# Epidemiology and Demographics
Cytochrome P450-oxidoreductase (POR) deficiency is a rere disease with unknown prevalence.

# Diagnosis

## Symptoms and physical Examination
- Severe Undervirilization in boys and severe virilization in girls but pubertal development in this disease is not studied enough.
- Antley-Bixler syndrome (ABS): craniofacial malformations (midface hypoplasia with low set ears and pear-shaped nose), arachnodactyly, clinodactyly, and radio-humeral synostosis.

## Laboratory Findings
Genetic testing is the gold standard of diagnosis. Pregnenolone, progesterone and 17-hydroxyprogesterone metabolites are increased and androgen metabolites are decreased.

# Treatment

## Medical Therapy
The mainstay of therapy for cytochrome P450-oxidoreductase deficiency is hydrocortisone to replace glucocorticoid deficiency. Gender-appropriate replacement of androgens or estrogens with progestins is necessary at the puberty time.
- Preferred regiemen: hydrocortisone oral, 15 to 25 mg/day in 2 to 3 divided doses.

## Surgery
The reconstruction surgery for ambiguous genitalia in genetically male patients may be applied.