Inborn errors of steroid metabolism

Editor-In-Chief: Prab R Tumpati, MD
Obesity, Sleep & Internal medicine
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Inborn errors of steroid metabolism
Synonyms	N/A
Pronounce	N/A
Specialty	N/A
Symptoms	Varies depending on specific disorder; may include ambiguous genitalia, adrenal insufficiency, hypertension, hypotension, virilization, feminization
Complications	Adrenal crisis, infertility, osteoporosis, metabolic syndrome
Onset	Congenital
Duration	Lifelong
Types	N/A
Causes	Genetic mutations affecting steroidogenesis
Risks	Family history of genetic disorders
Diagnosis	Genetic testing, hormone level testing, imaging studies
Differential diagnosis	Other forms of congenital adrenal hyperplasia, adrenal tumors, polycystic ovary syndrome
Prevention	N/A
Treatment	Hormone replacement therapy, surgery, glucocorticoid therapy
Medication	N/A
Prognosis	Varies; depends on specific disorder and treatment
Frequency	Rare; varies by specific condition
Deaths	N/A

Group of genetic disorders affecting steroid metabolism

Inborn errors of steroid metabolism are a group of genetic disorders that affect the biosynthesis and metabolism of steroids. These disorders result from mutations in the genes encoding enzymes involved in the steroidogenic pathway, leading to an accumulation or deficiency of specific steroid hormones. This can cause a variety of clinical manifestations depending on the specific enzyme affected and the role of the steroid hormones involved.

Introduction

Steroid hormones are crucial for a wide range of physiological processes, including growth, immune function, metabolism, and reproduction. They are synthesized from cholesterol through a series of enzymatic reactions occurring primarily in the adrenal glands, gonads, and placenta. Inborn errors of steroid metabolism can disrupt these pathways, leading to hormonal imbalances and clinical syndromes.

Pathophysiology

The steroidogenic pathway involves multiple steps, each catalyzed by a specific enzyme. Mutations in the genes encoding these enzymes can lead to:

• Enzyme deficiencies: Resulting in reduced production of downstream steroid hormones.
• Substrate accumulation: Leading to excess production of upstream precursors, which may be converted into alternative steroid products.

The clinical consequences depend on the specific enzyme affected and the resulting hormonal imbalance. Commonly affected pathways include the synthesis of glucocorticoids, mineralocorticoids, and sex steroids.

Common Disorders

Congenital Adrenal Hyperplasia (CAH)

Congenital adrenal hyperplasia is a group of disorders caused by enzyme deficiencies in the adrenal steroidogenic pathway. The most common form is 21-hydroxylase deficiency, leading to impaired synthesis of cortisol and aldosterone, with excess androgen production.

11β-Hydroxylase Deficiency

This condition results in impaired conversion of 11-deoxycortisol to cortisol, causing hypertension and virilization due to excess deoxycorticosterone and androgens.

17α-Hydroxylase Deficiency

A rare disorder characterized by hypertension and hypokalemia due to excess mineralocorticoids, with sexual infantilism due to deficient sex steroid production.

3β-Hydroxysteroid Dehydrogenase Deficiency

This disorder affects the conversion of pregnenolone to progesterone, leading to deficiencies in all steroid classes and ambiguous genitalia in genetic males.

Diagnosis

Diagnosis of inborn errors of steroid metabolism typically involves:

• Clinical evaluation: Assessment of symptoms and family history.
• Biochemical testing: Measurement of hormone levels in blood and urine.
• Genetic testing: Identification of mutations in genes encoding steroidogenic enzymes.

Management

Management strategies depend on the specific disorder and may include:

• Hormone replacement therapy: To correct deficiencies in cortisol, aldosterone, or sex steroids.
• Surgical intervention: For ambiguous genitalia or other anatomical abnormalities.
• Monitoring and supportive care: To manage complications such as hypertension or electrolyte imbalances.

See also

• Steroid hormone
• Adrenal gland
• Endocrinology
• Genetic disorder