Emergency Inherited Inborn Errors of Metabolism

Congenital Adrenal Hyperplasia (CAH)

Inherited Adrenal Steroidogenesis Enzyme Deficiency

Primary risk age: Neonates and infants (salt-wasting crises present in the first 2 weeks of life)

Urgency: Emergency
Typical age: Neonates and infants (salt-wasting crises present in the first 2 weeks of life)
Body system: Endocrine & Metabolic

Typical course: This is a lifelong autosomal recessive metabolic disorder requiring continuous daily hormone management.

Reviewed against AAP · CDC · WHO · NHS guidance Last reviewed 2026-06-13

1. Summary & Pathophysiology

Inherited Adrenal Steroidogenesis Enzyme Deficiency

Pathophysiology (Development Path)

Deficiency of 21-hydroxylase blocks the conversion of cholesterol precursors to cortisol and aldosterone. Deficient cortisol removes negative feedback on the pituitary, causing massive ACTH release. This overstimulates the adrenal cortex (hyperplasia), shunting accumulated precursors into androgen pathways, causing severe virilization.

Primary Causes & Etiology

Autosomal recessive mutation in the CYP21A2 gene, leading to a deficiency of the enzyme 21-hydroxylase.

2. Symptom Continuum

Early Onset Signs
Atypical external genitalia in newborn girls (clitoromegaly, labial fusion). Detected via routine newborn screening.
Progressive Phase
In salt-wasting CAH (75% of cases): vomiting, weight loss, progressive dehydration, and lethargy around 1 to 2 weeks of life.
Severe Indicators
Adrenal salt-wasting crisis: severe hypovolemic shock, hyponatremia, hyperkalemia, hypoglycemia, and death if untreated.

3. Clinical Verification

Elevated serum levels of 17-hydroxyprogesterone (17-OHP) on newborn screening. Confirmed with chromosomal karyotype and genetic testing.

4. Care & Elements Plan

Primary Care Treatment Plan

Initiate life-saving hormone replacement. Administer Hydrocortisone to suppress ACTH and excess androgens. Administer Fludrocortisone and sodium chloride supplements for salt-wasters. Implement stress dosing during illness.

Home Support Elements

Administer medications at exact scheduled times. Monitor for signs of vomiting or dehydration. Keep an emergency hydrocortisone injection kit. Coordinate pediatric endocrinology follow-up.

Generic Active Ingredients (No Brands)

Hydrocortisone (generic active glucocorticoid)
Fludrocortisone acetate (generic active mineralocorticoid)
Sodium chloride (salt supplements for infants).

Lists active elements only. Never administer self-designed therapies.

5. Doctor Critical Lines

Critical Thresholds: When to See a Doctor

Any newborn with atypical genitalia, or any infant showing poor feeding, vomiting, or excessive weight loss in the first weeks of life, requires immediate emergency evaluation.

6. Vaccine & Prevention

Routine Prophylaxis (Prevention)

Genetic counseling for carrier parents; prenatal treatment with dexamethasone to prevent virilization in female fetuses is controversial and requires expert monitoring.

Immunization Context

Routine pediatric vaccines are recommended; stress dosing may be required during febrile vaccine reactions.

7. Timelines & Outlook

Active Timeline

This is a lifelong autosomal recessive metabolic disorder requiring continuous daily hormone management.

Expected Prognosis

Excellent with early diagnosis and compliant hormone replacement; children achieve normal growth and fertility, though close monitoring of bone age is needed.

Potential Untreated Complications

Adrenal crisis, shock, severe electrolyte imbalances, short adult stature (due to advanced bone age), and virilization.

Severe

Phenylketonuria (PKU)

Inborn Error of Amino Acid Metabolism

Neonates (Screened at birth; symptoms develop over the first year if untreated)

Emergency

Classic Galactosemia

Inborn Error of Carbohydrate Metabolism

Neonates (Symptoms present within days of initiating milk feeding)