Congenital adrenal hyperplasia (CAH) is a group of rare genetic conditions that affect the adrenal glands, which are located above the kidneys. Adrenal glands make important hormones that affect your body in many ways:

• Cortisol helps your body respond to stress, control blood sugar, reduce inflammation, and manage energy.
• Aldosterone helps your body balance salt and water and keeps blood pressure steady.
• Androgens are important for growth, development, and overall health.

CAH happens when the adrenal glands are missing a key enzyme needed to make certain hormones, which causes hormone levels to get out of balance. The resulting imbalances can range from mild to serious or even life-threatening.

How Rare Is Congenital Adrenal Hyperplasia?

Overall, CAH is a rare condition that affects about 1 in every 15,000 to 20,000 people around the world. There are several known types, and each is caused by a deficiency in a different enzyme that helps make important hormones. Some types are more common than others.

This article explores how common each type of CAH is, who is most affected, and why these patterns happen.

Why Are Some Types More Common Than Others?

CAH can affect people of any sex, race, or background. However, some types are more common than others, and certain groups may be more likely to have higher rates of specific types. Here’s why:

• Some gene mutations (changes) are more common — Certain types happen because of mutations in specific genes. Some of these changes are more frequent, so those types of CAH are seen more often.
• Family and ethnic patterns — In some communities, a rare gene change may be passed down through generations. Called the genetic founder effect, this can make a specific type of CAH more common in that group.
• Newborn screening programs — Babies with more severe forms of CAH can have serious symptoms at birth and are often diagnosed early through routine newborn screening. Milder or rarer types may not be picked up as easily because they aren’t included in standard screening tests.

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

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 genes that cause CAH are located on nonsex chromosomes, which means the chance of inheriting CAH is the same for all sexes.

CAH can affect anyone, no matter their biological sex. However, symptoms can show up differently in males and females, which can affect how and when the condition is diagnosed and treated.

• Females with some types of CAH may be born with genitalia that look different than expected — not clearly male or female. This visible sign often leads to early testing and diagnosis right after birth.
• Males with CAH typically don’t have visible signs at birth, and their genitalia look typical, so the condition may not be noticed right away. It might be diagnosed later when symptoms of vomiting, dehydration, or early puberty appear.
• In milder forms like nonclassic CAH, serious symptoms like adrenal crisis are rare, and the condition may not be diagnosed until later in life.

What Are the Most Common Types of Congenital Adrenal Hyperplasia?

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

CAH due to 21-hydroxylase deficiency makes 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 CAH Due to 21-Hydroxylase Deficiency

The most common type of CAH is nonclassic CAH. Also called nonclassic 21-hydroxylase deficiency, it’s caused by mutations in the CYP21A2 gene, which leads to a lack of the enzyme 21-hydroxylase. This enzyme plays a key role in producing certain hormones.

Nonclassic CAH is milder than the classic form. Nonclassic CAH does not typically cause life-threatening complications and often goes undiagnosed until symptoms show up later in childhood, adolescence, or adulthood. The way the condition appears can vary, depending on the extent of the deficiency. Some people are diagnosed when they experience menstrual problems, while others are diagnosed only when they have fertility issues in adulthood.

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

Classic CAH Due to 21-Hydroxylase Deficiency

Classic 21-hydroxylase deficiency CAH is also caused by mutations in the CYP21A2 gene. Classic CAH is divided into two forms — salt-wasting and simple-virilizing CAH.

Salt-wasting CAH is the more severe form, affecting about 70 percent to 75 percent of individuals with classic CAH. It involves a deficiency in cortisol and aldosterone, which can make it hard for the body to keep the right balance of salt and water. People with this form also have too much androgen.

The milder form, simple-virilizing CAH, affects 25 percent to 30 percent of people with classic CAH. Cortisol is deficient, but salt and water levels are normal. Like in the salt-wasting type, too much androgen can cause unusual genital development and faster growth during childhood. Extra androgens can also make the growth plates close sooner, leading to shorter adult height. That’s why early diagnosis and adequate treatment are so important.

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

CAH Due to 11-Beta-Hydroxylase Deficiency

This form of CAH is caused when 11-beta-hydroxylase, which helps make key hormones like cortisol and aldosterone, is missing. When the enzyme isn’t working properly, the body can’t finish making these hormones. Instead, materials that were supposed to become cortisol and aldosterone get rerouted and turned into extra androgens and other substances that can raise blood pressure.

This hormone imbalance can lead to symptoms like early puberty, high blood pressure, and changes in genital development, especially in girls.

This type of CAH accounts for 5 percent to 8 percent of all CAH cases. It’s 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.

CAH Due to 17-Alpha-Hydroxylase Deficiency

This condition affects about 1 in 50,000 people worldwide, representing about 1 percent of CAH cases. It’s more frequently seen in Brazil, China, and Japan, due to genetic founder effects.

This rare form of CAH is caused by mutations in a gene called CYP17A1. This gene helps your body make an enzyme called 17-alpha-hydroxylase, which is important for producing several key hormones, including cortisol, aldosterone, and sex hormones like estrogen and testosterone. When the CYP17A1 gene doesn’t work properly, the body can’t make enough of these hormones. The hormone-building materials get rerouted, which has these effects:

• Extra mineralocorticoids are made instead of cortisol and sex hormones, which can lead to high blood pressure and low potassium.
• Lack of sex hormones can cause delayed or absent puberty, infertility, and genital differences, especially in people with XY chromosomes.

This enzyme is found in both the adrenal glands and the gonads (ovaries or testes), so the hormone imbalance affects both areas. Hormone replacement therapy may be needed to manage symptoms and help the body develop normally.

The Rarest Types of Congenital Adrenal Hyperplasia

The prevalence of the remaining rare 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 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.

CAH Due to 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 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 3-beta-hydroxysteroid dehydrogenase. This enzyme is essential for producing several important hormones, including cortisol, aldosterone, and sex hormones.

CAH Due to P450 Oxidoreductase Deficiency

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

A systematic review of past research from 2023 found 119 cases of PORD. A 2017 review, which put the number of known global cases at 140, reported one type 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. It’s also known as STAR protein deficiency because it’s caused by mutations in the steroidogenic acute regulatory protein (STAR) gene. STAR protein plays a critical role in moving cholesterol into the mitochondria (the energy centers of cells). Lipoid CAH results in the complete inability to produce adrenal steroids, causing a life-threatening salt-wasting crisis in infancy. Without early diagnosis and treatment, this condition is often fatal​​.

The prevalence of lipoid CAH is documented only in specific populations. It appears to be most common among Chinese, Japanese, Korean, and Palestinian Arab 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 diagnosing and managing it. Some forms, like classic CAH due to 21-hydroxylase deficiency, are more common, but 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, people share their experiences with congenital adrenal hyperplasia, get advice, and find support from others who understand.

Have you or a loved one been diagnosed with CAH? Which type? Let others know in the comments below.