Congenital adrenal hyperplasia (CAH) is a group of rare genetic conditions that affect the adrenal glands, which are located above the kidneys. These glands produce hormones like cortisol (a stress hormone), aldosterone (which helps balance salt and water), androgens (hormones involved in development and growth), as well as catecholamines (adrenaline and noradrenaline), which help your body respond to stressful or exciting situations. CAH occurs when there’s a lack of an enzyme that’s needed to properly make these hormones, leading to imbalances that can range from mild to life-threatening.

Overall, CAH is rare, affecting somewhere between 1 in 15,000 and 1 in 20,000 people worldwide. There are seven recognized types of CAH, each caused by a deficiency in a specific enzyme. Some forms are more common than others.

In this article, we’ll explore the prevalence of the different types of CAH, as well as which populations are most affected and why these patterns occur.

Why Are Some Types of CAH More Common Than Others?

CAH can affect people of all sexes and racial and ethnic backgrounds. However, some types of CAH are more common than others, and some are more common among certain populations. This may be due to:

• Common mutations (changes) in specific genes — Some types of CAH are more common because they are caused by mutations in genes that are more frequently affected.
• Genetic founder effects and ethnic differences — Certain groups have higher rates of specific types of CAH due to “genetic founder effects.” This happens when a small, isolated population passes down a specific genetic mutation over generations, making it more common in that group.
• Population-based newborn screening — Types of CAH that cause serious symptoms at birth are often detected early through newborn-screening programs. Rarer forms may not be diagnosed as often because they aren’t included in standard screening tests.

Does a Person’s Biological Sex Increase Their Risk for CAH?

CAH is an autosomal recessive condition, meaning a person inherits two copies of a mutated gene — one from each parent — to develop the condition. The affected genes are located on autosomes (nonsex chromosomes), so the likelihood of inheriting CAH is the same for people of any biological sex.

However, a person’s biological sex can influence how and when they’re diagnosed, because certain symptoms present differently in people of different sexes. For example:

• Females with some forms of CAH often present with ambiguous genitalia at birth. Ambiguous genitalia means the external genital structures don’t appear clearly male or female. This visible sign often leads to earlier diagnosis.
• Males with CAH typically don’t have visible signs at birth. In many types of CAH, male genitalia develop typically, so the condition may go undetected until other symptoms appear, such as adrenal crises in infancy or signs of early puberty. Nonclassic CAH is unlikely to cause adrenal crises, and healthcare professionals usually screen for classic CAH at birth, so this situation is rare.

While biological sex doesn’t affect the likelihood of inheriting CAH, it often plays a role in when and how the condition is identified.

What Are the Most Common Types of CAH?

Although CAH is quite rare in general, some types of CAH are more common than others.

CAH due to 21-hydroxylase deficiency is the most commonly diagnosed type of CAH, making up 95 percent of all CAH cases. This type can be broken down into classic CAH and nonclassic CAH, with nonclassic being more common.

Nonclassic 21-Hydroxylase Deficiency

Nonclassic CAH is the most common type of CAH. Also called nonclassic 21-hydroxylase deficiency, this type of CAH is caused by mutations in the CYP21A2 gene, which lead to a lack of the enzyme 21-hydroxylase. This enzyme plays a critical role in producing certain hormones. This form of CAH is milder. Unlike the classic form, nonclassic CAH does not typically cause life-threatening complications and often goes undiagnosed until symptoms appear later in childhood, adolescence, or adulthood. The way the condition presents can vary, depending on the extent of the deficiency: some biological females are diagnosed when they experience menstrual problems, while others are only diagnosed when they struggle with fertility in adulthood.

Nonclassic CAH is far more prevalent than classic CAH, affecting approximately 1 in 100 to 1 in 200 people in the general population. Certain groups have even higher rates; for example, it occurs in about 1 in 27 individuals in the Ashkenazi Jewish population, according to Endotext.

Classic 21-Hydroxylase Deficiency

Classic 21-hydroxylase deficiency — also simply called classic congenital adrenal hyperplasia — is also caused by mutations in the CYP21A2 gene.

Classic CAH is divided into two forms:

• Salt-wasting CAH — This is the more severe form, affecting about 70 percent to 75 percent of individuals with classic CAH. It involves too little aldosterone.
• Simple virilizing CAH — This milder form affects the remaining 25 percent to 30 percent of individuals with classic CAH. While salt and water levels are normal, too much androgen can cause unusual genital development and faster growth during childhood. Excess androgens can cause the growth plates to fuse together faster, resulting in a lower final stature (height). Therefore, early diagnosis is extremely important.

Classic CAH is rare in the general population, occurring in about 1 in 10,000 to 1 in 15,000 people in the United States and Europe. However, prevalence varies across different populations. For example, the Yupik Eskimo population experiences significantly higher rates, with about 1 in 282 children in this population being born with the salt-wasting form.

11-Beta-Hydroxylase Deficiency

This form of CAH is caused by a shortage of the enzyme 11-beta-hydroxylase, which helps make cortisol and hormones called corticosteroids. When the body doesn’t have enough 11-beta-hydroxylase, it can’t properly finish making these hormones. Instead, the ingredients (or building blocks) meant to create cortisol are turned into androgens. As a result, people with this condition have low cortisol and corticosteroid levels but high androgen levels, which can cause hormone imbalances.

This type accounts for 5 percent to 8 percent of all CAH cases. It is more common in specific populations, such as among certain groups within North Africa. Moroccan Jews, for example, are thought to have a higher rate of this type of CAH.

17 Alpha-Hydroxylase Deficiency

This condition affects about 1 in 1 million people worldwide, representing 1 about percent of CAH cases. It is more frequently observed in Brazil, China, and Japan, due to genetic founder effects discussed above.

As with classic CAH, this form of CAH is caused by mutations in a specific gene that disrupts hormone production in the adrenal glands. The affected gene is called CYP17A1 — not to be confused with the CYP21A2 gene that’s affected in classic CAH. The CYP17A1 gene provides instructions for making the enzyme 17a-hydroxylase, which is essential for producing mineralocorticoids (such as aldosterone, cortisol, and sex hormones like androgens and estrogens). A 17 alpha-hydroxylase deficiency affects both the adrenal glands and gonads because this enzyme is found in both types of glands.

The Rarest Types of CAH

The prevalence of the remaining three types of CAH is less certain. This is due to:

• Limited cases — These forms of CAH have been reported in only a small number of documented cases globally.
• Geographic and genetic differences — Cases may be geographically or genetically clustered in small populations, making it difficult to estimate global prevalence.
• Underdiagnosis — Symptoms of these rare forms can overlap with other medical conditions, and they may not be detected through standard newborn screening programs, further obscuring their prevalence.

3-Beta-Hydroxysteroid Dehydrogenase Deficiency

An extremely rare type of CAH, 3-beta-hydroxysteroid dehydrogenase deficiency has an estimated prevalence of less than 1 per 1 million live births. At least 61 unrelated families affected by 3-beta-hydroxysteroid dehydrogenase deficiency have been reported since 1962. Further, according to Medscape, 3-beta-hydroxysteroid dehydrogenase deficiency is relatively common in the Old Order Amish in North America.

This type of CAH is caused by mutations in the HSD3B2 gene, which provides instructions for making the 3-beta-hydroxysteroid dehydrogenase enzyme. This enzyme is essential for producing several important hormones, including cortisol, aldosterone, and sex hormones.

P450 Oxidoreductase Deficiency

In P450 oxidoreductase deficiency (PORD), mutations in the POR gene disrupt the function of the cytochrome P450 oxidoreductase enzyme. This enzyme is crucial for supporting other enzymes involved in producing certain steroids. When these enzymes don’t work properly, the body cannot produce a sufficient amount of cortisol, sex hormones, or others.

A systematic review of past research from 2023 found 119 documented cases of PORD. A review dated 2017 in GeneReviews puts the number of known global cases of PORD at 140. The latter review also reported one type of PORD to be more prevalent among people of Japanese ancestry and another to be more prevalent in individuals from European backgrounds.

Lipoid Congenital Adrenal Hyperplasia

Lipoid CAH is the rarest and most severe form of CAH. It is also known as “StAR protein deficiency” because it is caused by mutations in the steroidogenic acute regulatory protein (StAR). This protein plays a critical role in moving cholesterol into the mitochondria (the energy centers of cells). The condition results in the complete inability to produce adrenal steroids, causing a life-threatening salt-wasting crisis in infancy. Without early diagnosis and treatment, it is often fatal​​.

The prevalence of LCAH is documented only in specific populations. It appears to be most common among Chinese, Japanese, Korean, and Palestinian Arabs populations, with estimates in these groups suggesting an incidence of 1 in 250,000 to 1 in 300,000 births.

Take the Next Step

CAH is a complex group of conditions, but understanding its different types, causes, and how it affects individuals can make a big difference in managing it. While some forms, like classic 21-hydroxylase deficiency, are more common, others, such as lipoid CAH, are extremely rare but severe. Advances in genetic research and newborn screening programs have improved diagnosis and treatment, helping those with CAH lead healthier lives. If you or a loved one may be affected by CAH or are concerned about symptoms, talk to a healthcare provider. Early diagnosis and treatment are essential for the best outcomes.

Talk With Others Who Understand

On CAHteam, the site for people with congenital adrenal hyperplasia and their loved ones, people come together to gain a new understanding of CAH and share their stories with others who understand life with the condition.

Are you or a loved one diagnosed with CAH? Which type? Share your questions, experiences, and insights in the comments below.