Published: 18 Jun 2025

ICD9: 255.2      ICD10: E25.0      ICD11: 8A02.11

Hydroxylase deficiency is a group of genetic disorders that fall under the umbrella of Congenital Adrenal Hyperplasia (CAH).
These disorders affect the adrenal glands, which are responsible for producing vital hormones like cortisol, aldosterone, and androgens (male sex hormones).

The deficiency stems from a mutation in a gene that codes for a specific enzyme called a hydroxylase. This enzyme is crucial for the production of these hormones. The most common type of hydroxylase deficiency is 21-hydroxylase deficiency (21-OHD), but other less common types exist.

Here's a breakdown of the key aspects:

1. The Problem: Enzyme Deficiency

Hydroxylases are crucial for hormone production: Enzymes act as catalysts in chemical reactions. Hydroxylases are enzymes needed for the adrenal glands to synthesize cortisol, aldosterone, and androgens.
Genetic mutation: A mutation in the gene that codes for the hydroxylase enzyme results in a deficient or non-functional enzyme.
Impaired hormone production: With a deficient enzyme, the adrenal glands cannot produce enough cortisol and/or aldosterone.

2. Consequences of Hormone Deficiency

Cortisol deficiency: Cortisol helps regulate blood sugar, blood pressure, and the body's response to stress. Lack of cortisol can lead to:
Adrenal crisis: A life-threatening condition characterized by low blood sugar, low blood pressure, vomiting, dehydration, and shock.
Difficulty managing stress: Increased vulnerability to illness and difficulty coping with physical or emotional stress.
Aldosterone deficiency: Aldosterone helps regulate sodium and potassium levels in the blood, which are vital for blood pressure and fluid balance. Lack of aldosterone can lead to:
Salt-wasting: The body loses too much sodium and retains too much potassium. This can cause dehydration, low blood pressure, and heart problems.
Androgen excess: Because the body cannot produce cortisol and aldosterone efficiently, it tries to compensate by over-stimulating the adrenal glands. This leads to an overproduction of androgens. Excess androgens can cause:
Virilization in females: Development of male characteristics, such as ambiguous genitalia at birth, excessive facial and body hair, a deepened voice, and irregular menstruation.
Early puberty in males: Enlarged penis, premature development of secondary sexual characteristics.
Accelerated growth in children: Can result in shorter adult stature if not treated properly.

3. Types of Hydroxylase Deficiency

The most common type is 21-hydroxylase deficiency. Other rarer types include 11-beta-hydroxylase deficiency and 17-alpha-hydroxylase deficiency. Each type affects different enzymes and can lead to slightly different hormonal imbalances and symptoms.

21-Hydroxylase Deficiency (21-OHD): By far the most common type. There are two main forms:
Classical 21-OHD: The most severe form, often diagnosed at birth. It can be further subdivided into:
Salt-wasting: Affects both cortisol and aldosterone production.
Simple virilizing: Primarily affects cortisol production, with milder effects on aldosterone.
Non-classical 21-OHD (Late-onset): A milder form, often diagnosed later in childhood or adulthood. Individuals may have subtle symptoms like acne, excessive hair growth, and irregular periods.
11-beta-Hydroxylase Deficiency (11-OHD): The second most common type. It impairs the production of both cortisol and corticosterone. This leads to virilization and, often, hypertension (high blood pressure).
17-alpha-Hydroxylase Deficiency (17-OHD): This is a rare form that affects the production of both cortisol and sex hormones (androgens and estrogens). Individuals with this deficiency may have high blood pressure, low potassium levels, and delayed or absent puberty. Females may have absent uterus and ovaries, while males may have ambiguous genitalia or female genitalia.

4. Diagnosis and Treatment

Newborn screening: Many countries screen newborns for 21-OHD using a blood test that measures 17-hydroxyprogesterone (17-OHP) levels. Elevated 17-OHP is a sign that the adrenal glands are overproducing androgens due to a hydroxylase deficiency.
Blood tests: Blood tests can measure hormone levels (cortisol, aldosterone, androgens) to help diagnose and monitor the condition.
Genetic testing: Genetic testing can confirm the diagnosis and identify the specific mutation causing the deficiency.
Treatment: Treatment typically involves hormone replacement therapy with glucocorticoids (like hydrocortisone) to replace the deficient cortisol. Mineralocorticoids (like fludrocortisone) may also be needed to replace aldosterone in salt-wasting forms. In some cases, surgery may be necessary to correct ambiguous genitalia in females.

5. Importance of Early Diagnosis and Treatment

Early diagnosis and treatment are crucial to prevent adrenal crises, promote normal growth and development, and manage the symptoms of androgen excess. With proper treatment, individuals with hydroxylase deficiency can live healthy and fulfilling lives.

In summary, hydroxylase deficiency is a genetic disorder that affects the adrenal glands, leading to hormonal imbalances. The most common form is 21-hydroxylase deficiency. The condition is diagnosed through blood tests and genetic testing, and treatment involves hormone replacement therapy. Early diagnosis and treatment are essential for preventing serious complications.

If you suspect you or someone you know may have hydroxylase deficiency, it's vital to consult with a doctor, especially an endocrinologist, for proper diagnosis and management.