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Disease Profile

Congenital adrenal hyperplasia

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 100 000

3,310 - 29,790

US Estimated

1-9 / 100 000

5,135 - 46,215

Europe Estimated

Age of onset

All ages

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ICD-10

E25.0

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

CAH

Summary

Congenital adrenal hyperplasia (CAH) refers to a group of genetic conditions that affect the adrenal glands. These glands sit on top of the kidneys and are responsible for releasing various types of hormones that the body needs to function. Affected people lack an enzyme the adrenal glands need to make one or more of these hormones and often overproduce androgens (male hormones such as testosterone).[1] The signs and symptoms present in each person depend on many factors including the type of CAH, the age of diagnosis, and the sex of the affected person. For example, females with a severe form of the condition may have ambiguous genitalia at birth and if not properly diagnosed, develop dehydration, poor feeding, diarrhea, vomiting and other health problems soon after. People with milder forms may not be diagnosed with the condition until adolescence or adulthood when they experience early signs of puberty or fertility problems. Treatment for CAH varies but may include medication and/or surgery.[2][3]

Symptoms

The signs and symptoms of congenital adrenal hyperplasia (CAH) vary based on many factors including the type of CAH, the age of diagnosis and the sex of the affected person. For example, girls with the severe form of CAH may be born with ambiguous genitalia, which often allows the condition to be diagnosed before other associated health problems such as poor feeding, vomiting, dehydration, and abnormal heart beat, can develop. Males typically appear unaffected at birth even when they have a severe form of CAH and without proper diagnosis, will develop associated health problems within 2-3 weeks after birth. Both genders can experience other symptoms such as early onset of puberty, fast body growth, and premature completion of growth leading to short stature, if they are not treated in early life.[4][1][2]

People affected by milder forms may not have any signs and symptoms of CAH during childhood. In these cases, a diagnosis may not be made until adolescence or adulthood when the affected person experiences early signs of puberty or fertility problems. Females with this type may have excessive facial or body hair; irregular menstrual periods; and/or acne.[4][1][2]

There are two main types of CAH: classic CAH, the more severe form, and a milder form called nonclassic CAH. For a detailed description of the signs and symptoms found in each type of CAH, please click here.[3]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormality of metabolism/homeostasis
Laboratory abnormality
Metabolism abnormality

[ more ]

0001939
Accelerated skeletal maturation
Advanced bone age
Early bone maturation

[ more ]

0005616
Cryptorchidism
Undescended testes
Undescended testis

[ more ]

0000028
Female pseudohermaphroditism
0010458
Hypertension
0000822
Hypospadias
0000047
Increased circulating cortisol level
0003118
30%-79% of people have these symptoms
Failure to thrive in infancy
Faltering weight in infancy
Weight faltering in infancy

[ more ]

0001531
Feeding difficulties in infancy
0008872
Percent of people who have these symptoms is not available through HPO
Abnormal thorax morphology
Abnormality of the chest
0000765
Abnormality of the urinary system
Urinary tract abnormalities
Urinary tract abnormality
Urinary tract anomalies

[ more ]

0000079
Absent scrotum
0008707
Adrenal hyperplasia
Enlarged adrenal glands
0008221
Adrenogenital syndrome
0000840
Ambiguous genitalia
Ambiguous external genitalia
Ambiguous external genitalia at birth
Intersex genitalia

[ more ]

0000062
Ambiguous genitalia, female
Atypical appearance of female genitals
0000061
Autosomal recessive inheritance
0000007
Bifid scrotum
Cleft of scrotum
0000048
Clitoral hypertrophy
Enlarged clitoris
0008665
Congenital adrenal hyperplasia
0008258
Decreased circulating aldosterone level
Low blood aldosterone level
0004319
Decreased circulating renin level
0003351
Decreased testicular size
Small testes
Small testis

[ more ]

0008734
Growth abnormality
Abnormal growth
Growth issue

[ more ]

0001507
Gynecomastia
Enlarged male breast
0000771
Hyperpigmentation of the skin
Patchy darkened skin
0000953
Hypoglycemia
Low blood sugar
0001943
Hypokalemia
Low blood potassium levels
0002900
Hypokalemic alkalosis
0001949
Hypoplasia of the uterus
Small uterus
Underdeveloped uterus

[ more ]

0000013
Hypoplasia of the vagina
Underdeveloped vagina
0008726
Long penis
Enlarged penis
0000040
Male pseudohermaphroditism
0000037
Micropenis
Short penis
Small penis

[ more ]

0000054
Neonatal onset
0003623
Precocious puberty in males
Early onset of puberty in males
0008185
Premature pubarche
Premature pubic hair growth
0012411
Primary amenorrhea
0000786
Recurrent fever
Episodic fever
Increased body temperature, episodic
Intermittent fever

[ more ]

0001954
Renal salt wasting
Loss of salt in urine
0000127
Short stature
Decreased body height
Small stature

[ more ]

0004322

Cause

Congenital adrenal hyperplasia (CAH) is a group of genetic conditions that can be caused by a change (mutation) in several different genes:[2]

Most of these genes encode enzymes that the adrenal glands need to make one or more hormones. The adrenal glands are cone-shaped organs that sit on top of the kidneys and are responsible for releasing various types of hormones that the body needs to function. Mutations in these genes lead to deficient levels of enzymes which cause low levels of hormones such as cortisol and/or aldosterone and an overproduction of androgens (male hormones such as testosterone). Cortisol is a hormone that affects energy levels, blood sugar levels, blood pressure, and the body's response to stress, illness, and injury. Aldosterone helps the body maintain the proper level of sodium (salt) and water and helps maintain blood pressure. Irregular levels of these hormones lead to the signs and symptoms of CAH.[3][4]

Diagnosis

Yes, genetic testing is available for many of the genes known to cause congenital adrenal hyperplasia (CAH).[5] Carrier testing for at-risk relatives and prenatal testing are possible if the disease-causing mutations in the family are known.

The Genetic Testing Registry (GTR) is a centralized online resource for information about genetic tests. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Shortly after birth, all newborns in the United States are screened for a variety of conditions, including 21-hydroxylase deficiency. This is the most common cause of congenital adrenal hyperplasia (CAH) and accounts for 95% of classic CAH cases. Nonclassic CAH is not detected through newborn screening and is often not suspected until signs and symptoms of the condition begin to appear later in childhood or early adulthood. In these cases, a diagnosis of CAH is usually based on physical examination; blood and urine tests that measure hormone levels; and/or genetic testing. An X-ray may also be helpful in confirming the diagnosis in children since CAH can cause bones to grow and develop more quickly than usual (advanced bone age) .[2][3][4]

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Newborn Screening

    • An ACTion (ACT) sheet is available for this condition that describes the short-term actions a health professional should follow when an infant has a positive newborn screening result. ACT sheets were developed by experts in collaboration with the American College of Medical Genetics.
    • An Algorithm flowchart is available for this condition for determining the final diagnosis in an infant with a positive newborn screening result. Algorithms are developed by experts in collaboration with the American College of Medical Genetics.
    • Baby's First Test is the nation's newborn screening education center for families and providers. This site provides information and resources about screening at the local, state, and national levels and serves as the Clearinghouse for newborn screening information.
    • The Newborn Screening Coding and Terminology Guide created by the National Library of Medicine (NLM) at the National Institutes of Health (NIH) promotes and facilitates the use of electronic health data standards in recording and transmitting newborn screening test results. The Web site includes standard codes and terminology for newborn tests and conditions for which they screen, and links to related sites. Click on the links to below view details for this condition.
      Congenital adrenal hyperplasia (due to 11-beta-hydroxylase deficiency)
      Congenital adrenal hyperplasia (non-classical)
      Congenital adrenal hyperplasia (salt-wasting)
      Congenital adrenal hyperplasia (simple virilizing)
    • National Newborn Screening and Global Resource Center (NNSGRC) provides information and resources in the area of newborn screening and genetics to benefit health professionals, the public health community, consumers and government officials.

      Treatment

      The best treatment options for congenital adrenal hyperplasia (CAH) depend on many factors including the type of CAH and the signs and symptoms present in each person. Many people with CAH require steroids to replace the low hormones. These medications will need to be taken daily throughout life or the symptoms of CAH may return. It is important that affected people on medications be closely followed by their healthcare provider because their dose may need to be adjusted at different times in life such as periods of high stress or illness.

      Girls with severe CAH who are born with ambiguous genitalia may undergo surgery to ensure proper function and/or to make the genitals look more female.[2][3][4]

      For more information on the treatment of CAH, please click here.

      Organizations

      Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

      Organizations Supporting this Disease

        Learn more

        These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

        Where to Start

          In-Depth Information

          • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
          • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
          • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
          • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
            21-hydroxylase deficiency
            17-hydroxylase deficiency
            11-beta-hydroxylase deficiency
            3-beta-hydroxysteroid dehydrogenase deficiency
            Congenital lipoid adrenal hyperplasia
          • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
          • PubMed is a searchable database of medical literature and lists journal articles that discuss Congenital adrenal hyperplasia. Click on the link to view a sample search on this topic.

            References

            1. Congenital adrenal hyperplasia. MedlinePlus. February 2014; https://www.nlm.nih.gov/medlineplus/ency/article/000411.htm.
            2. Congenital Adrenal Hyperplasia. National Organization of Rare Disorders (NORD). Updated 2018; . https://rarediseases.org/rare-diseases/congenital-adrenal-hyperplasia/.
            3. Congenital Adrenal Hyperplasia. Eunice Kennedy Shriver National Institute of Child Health and Human Development. July 2013; https://www.nichd.nih.gov/health/topics/cah/Pages/default.aspx.
            4. Thomas A Wilson, MD. Congenital Adrenal Hyperplasia. Medscape Reference. April 2014; https://emedicine.medscape.com/article/919218-overview.
            5. Congenital Adrenal Hyperplasia. Genetic Testing Registry. https://www.ncbi.nlm.nih.gov/gtr/conditions/C0001627/. Accessed 12/27/2014.

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