3 beta-hydroxysteroid dehydrogenase deficiency

# Overview
3 beta-hydroxysteroid dehydrogenase deficiency is a rare disease due to congenital adrenal hyperplasia. It is characterized by impaired biosynthesis pathway of progestins, mineralocorticoids, glucocorticoids, and androgens. As a result of cortisol absence, corticotropin (ACTH) secretion increases and leads to produce 3-hydroxy-delta-5-steroids pregnenolone, 17-hydroxypregnenolone, and dehydroepiandrosterone (DHEA), also their sulfates. In peripheral tissues the conversion of DHEA sulfate (DHEAS) to testosterone, is responsible for virilization in females. 3 beta-hydroxysteroid dehydrogenase deficiency is caused by a mutation in the HSD3B2 gene. Symptoms of 3 beta-hydroxysteroid dehydrogenase deficiency may include symptoms of both cortisol and aldosterone deficiency such as feeding difficulties, vomiting, volume depletion, undervirilization in newborn males, and mild virilization and clitoromegaly in newborn female. Diagnosis for 3 beta-hydroxysteroid dehydrogenase deficiency is based on delta-5-17-hydroxypregnenolone high levels in serum laboratory tests. The mainstay of therapy for this disease is hydrocortisone and fludrocortisone acetate. The reconstruction surgery for ambiguous genitalia in genetically male patients may be applied.

# Historical Perspective
3 beta-hydroxysteroid dehydrogenase deficiency was first time described in 1962, in a patient with ambiguous genitalia and salt wasting.

# Classification
There are two types of 3 beta-hydroxysteroid dehydrogenase deficiency:
- Salt-wasting
- Non-salt-wasting

# Pathophysiology
The pathogenesis of 3 beta-hydroxysteroid dehydrogenase deficiency is characterized by impaired pathway of biosynthesis of progestins, mineralocorticoids, glucocorticoids, and androgens. As a result of cortisol absence, corticotropin (ACTH) secretion increases the production of 3-hydroxy-delta-5-steroids pregnenolone, 17-hydroxypregnenolone, and dehydroepiandrosterone (DHEA). ACTH secretion also increases the production of their sulfates. In peripheral tissues the conversion of DHEA sulfate (DHEAS) to testosterone is responsible for virilization in females.

# Causes
3 beta-hydroxysteroid dehydrogenase deficiency is caused by a mutation in the HSD3B2 gene.

# Differentiating 3 Beta-hydroxysteroid Dehydrogenase Deficiency From Other Diseases

## Differentials of ambiguous genitalia
3 beta-hydroxysteroid dehydrogenase deficiency must be differentiated from diseases that cause ambiguous genitalia:

## Differentials based on virilization and hirsutism
3 beta-hydroxysteroid dehydrogenase deficiency must be differentiated from diseases that cause virilization and hirsutism in female:

# Epidemiology and Demographics
The prevalence of 3 beta-hydroxysteroid dehydrogenase deficiency is unknown. At least 60 affected individuals have been reported.

# Risk Factors
Common risk factors in the development of 3 beta-hydroxysteroid dehydrogenase deficiency is family history of this disease.

# Diagnosis

## Symptoms
Symptoms of 3 beta-hydroxysteroid dehydrogenase deficiency may include symptoms of both cortisol and aldosterone deficiency such as feeding difficulties, vomiting, volume depletion, muscle weakness, undervirilization in male newborns, and mild virilization and clitoromegaly in newborn female. 

## Physical Examination
Physical examination may be remarkable for:
- Undervirilization in newborn males
- Mild virilization and clitoromegaly in newborn female.

## Laboratory Findings
Diagnosis for 3 beta-hydroxysteroid dehydrogenase deficiency is based on high levels of delta-5-17-hydroxypregnenolone.  Other laboratory findings incliude, hyponatremia and hyperkalemia.

# Treatment

## Medical Therapy
The mainstay of therapy for 3 beta-hydroxysteroid dehydrogenase deficiency is hydrocortisone and fludrocortisone acetate adiminstration. Gender-appropriate replacement of androgens or estrogens with progestins is necessary at the puberty time.
The goal of therapy includes the following: 
- Correct the effects of mineralocorticoid excess
- Prevent glucocorticoid deficiency
- Restore desired secondary sexual characteristics
- Treatment for 3 beta-hydroxysteroid dehydrogenase deficiency is by the use of glucocorticoids such as:
Preferred regimen (1): Hydrocortisone 10 to 25 mg/m2 body surface area/day PO.
Preferred regimen (2): Prednisolone 0.1 mg/kg/day PO.
Preferred regimen (3): Dexamethasone up to 0.5 mg/day PO.
- Preferred regimen (1): Hydrocortisone 10 to 25 mg/m2 body surface area/day PO.
- Preferred regimen (2): Prednisolone 0.1 mg/kg/day PO.
- Preferred regimen (3): Dexamethasone up to 0.5 mg/day PO.

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