Congenital adrenal hyperplasia due to 3-beta-hydroxysteroid dehydrogenase deficiency

What it is

From: Orphanet

A rare form of congenital adrenal hyperplasia (CAH) due to 3-beta-hydroxysteroid dehydrogenase (HSD3B2) deficiency and characterized by salt-wasting and non-salt wasting CAH with a wide variety of symptoms, including glucocorticoid and mineralocorticoid deficiencies in both sexes. Salt wasting can lead to dehydration and hypotension in the first few weeks of life. Affected males had undervirilization manifesting as a micropenis to severe perineoscrotal hypospadias. Females show normal or mildly virilized external genitalia (mild clitoromegaly, labial fusion) due to dehydroepiandrosterone (DHEA) accumulation and conversion to androgens by the normal HSD3B1.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Congenital adrenal hyperplasia · Very frequent (99-80%)

A type of adrenal hyperplasia with congenital onset.

Abnormal serum dehydroepiandrosterone level · Frequent (79-30%)

A deviation from the normal concentration of dehydroepiandrosterone in the circulation.

Adrenocorticotropic hormone excess · Frequent (79-30%)

Overproduction of adrenocorticotropic hormone (ACTH), which generally leads secondarily to overproduction of cortisol by the adrenal cortex.

Ambiguous genitalia, female · Frequent (79-30%)

Ambiguous genitalia in an individual with XX genetic gender.

Ambiguous genitalia, male · Frequent (79-30%)

Ambiguous genitalia in an individual with XY genetic gender.

Clitoral hypertrophy · Frequent (79-30%)

Hypertrophy of the clitoris.

Decreased circulating aldosterone level · Frequent (79-30%)

Abnormally reduced levels of aldosterone.

Decreased circulating cortisol level · Frequent (79-30%)

Abnormally reduced concentration of cortisol in the blood.

Elevated circulating 17-hydroxyprogesterone · Frequent (79-30%)

An increased level of 17-hydroxyprogesterone in the blood. 17-hydroxyprogesterone is an intermediate steroid in the adrenal biosynthetic pathway from cholesterol to cortisol and is the substrate for steroid 21-hydroxylase.

Gynecomastia · Frequent (79-30%)

Abnormal development of large mammary glands in males resulting in breast enlargement.

Hyperkalemia · Frequent (79-30%)

The concentration of potassium(1+) in the blood circulation is above the upper limit of normal.

Hyperpigmentation of the skin · Frequent (79-30%)

A darkening of the skin related to an increase in melanin production and deposition.

Hyponatremia · Frequent (79-30%)

The concentration of sodium in the blood circulation is below the lower limit of normal.

Hypospadias · Frequent (79-30%)

Abnormal position of urethral meatus on the ventral penile shaft (underside) characterized by displacement of the urethral meatus from the tip of the glans penis to the ventral surface of the penis, scrotum, or perineum.

Other findings in the same source

From: Orphanet

Additional reported features include Hypotension (Frequent (79-30%)); Increased circulating androstenedione concentration (Frequent (79-30%)); Increased circulating renin level (Frequent (79-30%)); Increased serum testosterone level (Frequent (79-30%)); Renal salt wasting (Frequent (79-30%)); Vomiting (Frequent (79-30%)); Decreased fertility in males (Frequent (79-30%)); Decreased serum testosterone concentration (Frequent (79-30%)); Dehydration (Frequent (79-30%)); Neonatal hypoglycemia (Frequent (79-30%)). This is a selected summary, not a complete description of the condition.

When it may begin

From: Orphanet

Infancy; Neonatal

Inheritance in the source

From: Orphanet

Autosomal recessive

Frequency and the population described

From: Orphanet

Reported case(s): 68.0; Worldwide. This is a published case count, not prevalence. Point prevalence: <1 / 1 000 000; Worldwide; Class only.

Understanding the inheritance label

From: MedlinePlus Genetics

An autosomal recessive pattern usually involves disease-causing changes in both copies of a gene. Parents may each carry one altered copy without having the condition themselves. A genetic counsellor can explain carrier testing and reproductive implications using the actual laboratory findings, rather than the condition name alone.

Which doctor should you see?

The suggested department for discussing Congenital adrenal hyperplasia due to 3-beta-hydroxysteroid dehydrogenase deficiency is Clinical Genetics, with a clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with clinical geneticist referral.

Additional services that may be relevant, depending on the findings, include: Nephrology.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Does the exact genetic or chromosome finding explain the observed features?
• Would a genetic counsellor help the family understand the result?
• Which organ-specific assessments are appropriate for this particular diagnosis?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Congenital adrenal hyperplasia due to 3-beta-hydroxysteroid dehydrogenase deficiency. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.