3-beta-hydroxysteroid dehydrogenase deficiency
Adrenal hyperplasia 2; Adrenal hyperplasia II; 3b-hydroxysteroid dehydrogenase deficiency; HSD3B deficiency; 3-beta-HSD deficiency; Type II 3-beta-hydroxysteroid dehydrogenase deficiency; CAH due to 3-beta-hydroxysteroid dehydrogenase deficiency; Congenital adrenal hyperplasia due to 3-beta-hydroxysteroid dehydrogenase deficiency
3-beta-hydroxysteroid dehydrogenase (3BHSD) deficiency is a form of congenital adrenal hyperplasia, a group of conditions that interfere with the body's ability to make hormones. People with this condition lack many of the hormones made in the gonads (testes or ovaries) and the adrenal glands.
3-beta-hydroxysteroid dehydrogenase (3BHSD) deficiency is very rare. Only 60 affected individuals have been reported.
There are three types of 3BHSD deficiency - the salt-wasting form, non-salt-wasting form, and non-classic form.
- 3BHSD deficiency is caused by changes (mutations) in the HSD3B2 gene.
- The HSD3B2 gene provides instructions for making the 3β-HSD enzyme.
- This enzyme is found in the gonads and adrenal glands.
- The 3β-HSD enzyme is involved in the production of many hormones, including cortisol, aldosterone, androgens, and estrogen.
- 3β-HSD deficiency is caused by a deficiency (shortage) of the 3β-HSD enzyme.
- Individuals with the salt-wasting type have HSD3B2 gene mutations that result in the production of very little or no enzyme.
- People with the non-salt-wasting type of this condition have HSD3B2 gene mutations that allow the production of some functional enzyme, although in reduced amounts.
This condition is inherited in an autosomal recessive manner.
Signs and symptoms
- Signs and symptoms depend on the type of 3BHSD deficiency; the age at diagnosis; and the sex of the affected person.
- The salt-wasting form is the most severe type and can even be life-threatening.
- People with this form are generally diagnosed at birth due to symptoms related to abnormal salt reabsorption (i.e. dehydration, poor feeding, vomiting). Males with any form of the condition often have abnormalities of the external genitalia and are frequently infertile.
- Females with the condition may have slight genital abnormalities at birth, but often go on to experience irregular menstruation, hirsutism, and infertility as they get older.
For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.
80%-99% of people have these symptoms
- Abnormal oral glucose tolerance
- Abnormal sex determination
- Abnormality of the menstrual cycle
- Accelerated skeletal maturation(Advanced bone age)
- Adrenocorticotropic hormone excess
- Adrenogenital syndrome
- Ambiguous genitalia, male(Ambiguous genitalia in males)
- Androgen insufficiency
- Congenital adrenal hyperplasia
- Cryptorchidism(Undescended testes)
- Decreased circulating aldosterone level(Low blood aldosterone level)
- Decreased circulating cortisol level(Low blood cortisol level)
- Delayed puberty(Delayed pubertal development)
- Delayed skeletal maturation(Delayed bone maturation)
- Elevated circulating follicle stimulating hormone level
- Elevated circulating luteinizing hormone level
- Feeding difficulties(Feeding problems)
- Female external genitalia in individual with 46,XY karyotype
- Generalized hyperpigmentation
- Hyperkalemia(Elevated serum potassium levels)
- Hyponatremia(Low blood sodium levels)
- Hypotension(Low blood pressure)
- Hypovolemia(Depleted blood volume)
- Increased circulating ACTH level(High blood corticotropin levels)
- Increased circulating renin level(Elevated blood renin level)
- Male pseudohermaphroditism
- Neonatal hypoglycemia(Low blood sugar in newborn)
- Perineal hypospadias
- Premature adrenarche
- Renal salt wasting(Loss of salt in urine)
- Urogenital sinus anomaly
- Vomiting(Throwing up)
30%-79% of people have these symptoms
- Absence of secondary sex characteristics
- Ambiguous genitalia, female(Atypical appearance of female genitals)
- Bifid scrotum(Cleft of scrotum)
- Clitoral hypertrophy(Enlarged clitoris)
- Decreased fertility in females(Reduced fertility in females)
- Decreased fertility in males
- Decreased testicular size(Small testes)
- Enlarged polycystic ovaries(Enlarged ovaries with cysts)
- Gynecomastia(Enlarged male breast)
- Hyperpigmented genitalia(Increased genital pigmentation)
- Insulin resistance(Body fails to respond to insulin)
5%-29% of people have these symptoms
- Abnormality of the labia majora(Abnormality of vaginal lips)
- Ectopic adrenal gland(Abnormal adrenal gland position)
- Hirsutism(Excessive hairiness)
Molecular Genetics Tests may includeː
- Sequence analysis of the entire coding region
- Mutation scanning of the entire coding region
- Deletion/duplication analysis
- Targeted variant analysis
- Sequence analysis of select exons
Biochemical Genetics Tests may includeː
- Enzyme assay
- People with the salt-wasting form of 3-beta–hydroxysteroid dehydrogenase (3BHSD) deficiency need replacement of glucocorticoids, mineralocorticoids, and sex steroids.
- This may include:
- Oral hydrocortisone (or other glucocorticoid) - hydrocortisone tablets are the preferred choice for treatment. In children, premixed, oral suspensions of hydrocortisone and long-acting glucocorticoid preparations should be avoided.
- Mineralocorticoid replacement by oral fludrocortisone acetate - those with non–salt-losing forms do not need mineralocorticoid replacement.
- Sex steroid replacement at puberty for those with a complete deficiency - including testosterone in males and cyclic estrogen-progesterone therapy in females. This promotes development of secondary sexual characteristics in both males and females, and cyclic menstrual bleeding in females with normal female chromosomes.
- In people with late-onset (non-classic) 3BHSD deficiency, the need for replacement therapy varies depending on the severity of the condition. Glucocorticoid replacement suppresses excess male hormones (androgens) in children with premature onset of puberty. In pubertal and post-pubertal females with the late-onset form, glucocorticoid replacement alone may correct menstrual irregularities and infertility, and decrease hirsutism and acne.
- The long-term outlook (prognosis) for people with 3BHSD deficiency is usually good-to-excellent with adequate replacement glucocorticoid and mineralocorticoid therapy (if needed) and monitoring.
- Because the enzyme deficiency is inherited and caused by genetic mutations present from birth, the condition will inherently be present (i.e. enzyme production will not increase during an affected person's lifetime).
- Males with poorly-controlled congenital adrenal hyperplasia (CAH) are at risk for benign testicular adrenal rest tumors.
NIH genetic and rare disease info
3-beta-hydroxysteroid dehydrogenase deficiency is a rare disease.
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