In the adrenal cortex, cholesterol is metabolized, producing mineralocorticoids such as aldosterone. Aldosterone regulates plasma sodium (Na+), and potassium (K+) levels. In another metabolic pathway, cortisol is produced. Cortisol is essential for maintaining circulation and blood sugar levels and is primarily released during stress. In another metabolic pathway, androgens (male sexual hormones) are formed. Enzymes accelerate these breakdown processes. When these enzymes are absent or altered, the breakdown process is slowed down.

Congenital adrenal hyperplasia (CAH) refers to disorders named after defects or deficiencies of these enzymes in the adrenal gland. 

Homozygous Congenital Adrenal Hyperplasia (CAH) Adreno genital Syndrom (AGS)

Congenital adrenal hyperplasia (CAH) is an autosomal recessive genetic disorder that affects the adrenal glands’ ability to produce cortisol, aldosterone, and androgens. CAH can be either homozygous or heterozygous, depending on the genetic makeup of the individual. The most common form is a deficiency of 21-hydroxylase (95%, 11-beta-hydroxylase deficiency (approximately 4-5%)). This leads to an increase in androgens.

Homozygous Congenital Adrenal Hyperplasia (CAH) Adreno genital Syndrom (AGS)

  • Definition: Homozygous individuals have two copies of the mutated gene, one inherited from each parent.
  • Phenotype: These individuals typically present with clinical symptoms of CAH, which may vary in severity depending on the specific enzyme deficiency.
  • Common Types:
    1. 21-hydroxylase deficiency (CYP21A2 mutation)
      • Classic Salt-Wasting
      • Simple Virilizing
    2. 11β-hydroxylase deficiency (CYP11B1 mutation)
    3. 17α-hydroxylase deficiency (CYP17A1 mutation)
    4. 3β-hydroxysteroid dehydrogenase deficiency (HSD3B2 mutation)
    5. Congenital lipoid adrenal hyperplasia (StAR mutation)
    6. P450 oxidoreductase deficiency (POR mutation)

Heterozygous Congenital Adrenal Hyperplasia (Carrier)

  • Definition: Heterozygous individuals carry one normal allele and one mutated allele of the gene responsible for CAH.
  • Phenotype: Typically asymptomatic but may exhibit mild hormonal abnormalities or subtle clinical features.
  • Characteristics:
    • Generally do not have full-blown CAH symptoms.
    • May have slightly elevated androgen levels.
    • In females, this can sometimes result in mild symptoms such as hirsutism or irregular menstruation.

Summary of Genetic Patterns:

  • Homozygous (Affected): Two mutated alleles → Clinical symptoms of CAH.
  • Heterozygous (Carrier): One normal allele + One mutated allele → Usually asymptomatic, potential mild hormonal changes.

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Clinical Symptoms, Diagnosis and Treatment see adrenogenital syndrom

adrenal hormones pathway