3 beta-hydroxysteroid dehydrogenase deficiency
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mehrian Jafarizade, M.D [2]
Overview
Historical Perspective
3 beta-hydroxysteroid dehydrogenase deficiency first time described in 1962, in a patient with ambiguous genitalia and salt wasting.[1]
Classification
There are two types of 3 beta-hydroxysteroid dehydrogenase deficiency: the salt-wasting, and non-salt-wasting type.
Pathophysiology
The pathogenesis of 3 beta-hydroxysteroid dehydrogenase deficiency is characterized by impaired pathway biosynthesis 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.[1]
Causes
3 beta-hydroxysteroid dehydrogenase deficiency is caused by a mutation in the HSD3B2 gene.
Differentiating 3 beta-hydroxysteroid dehydrogenase deficiency from other Diseases
3 beta-hydroxysteroid dehydrogenase deficiency must be differentiated from other diseases that cause ambiguous genitalia such as: 21-hydroxylase deficiency, 11-β hydroxylase deficiency, 17 alpha-hydroxylase deficiency, gestational hyperandrogenism and P450-oxidoreductase deficiency.
Epidemiology and Demographics
The prevalence of 3 beta-hydroxysteroid dehydrogenase deficiency is unknown. At least 60 affected individuals have been reported.[2]
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 newborn males, and mild virilization and clitoromegaly in newborn female. [3]
Physical Examination
Physical examination may be remarkable for: undervirilization in newborn males and mild virilization and clitoromegaly in newborn female.
Laboratory Findings
Diagnosis for 3 beta-hydroxysteroid dehydrogenase deficiency is based on delta-5-17-hydroxypregnenolone high levels. [4] Other laboratory findings include: hyponatremia, hyperkalemia.
Treatment
Medical Therapy
The mainstay of therapy for 3 beta-hydroxysteroid dehydrogenase deficiency is hydrocortisone and fludrocortisone acetate. Gender-appropriate replacement of androgens or estrogens with progestins is necessary at the puberty time.
Surgery
The reconstruction surgery for ambiguous genitalia in genetically male patients may be applied.
References
- ↑ 1.0 1.1 BONGIOVANNI AM (1962). "The adrenogenital syndrome with deficiency of 3 beta-hydroxysteroid dehydrogenase". J. Clin. Invest. 41: 2086–92. doi:10.1172/JCI104666. PMC 291138. PMID 13968789.
- ↑ "3-beta-hydroxysteroid dehydrogenase deficiency - Genetics Home Reference".
- ↑ Simard J, Rheaume E, Mebarki F, Sanchez R, New MI, Morel Y, Labrie F (1995). "Molecular basis of human 3 beta-hydroxysteroid dehydrogenase deficiency". J. Steroid Biochem. Mol. Biol. 53 (1–6): 127–38. PMID 7626445.
- ↑ Lutfallah C, Wang W, Mason JI, Chang YT, Haider A, Rich B, Castro-Magana M, Copeland KC, David R, Pang S (2002). "Newly proposed hormonal criteria via genotypic proof for type II 3beta-hydroxysteroid dehydrogenase deficiency". J. Clin. Endocrinol. Metab. 87 (6): 2611–22. doi:10.1210/jcem.87.6.8615. PMID 12050224.