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Disease Profile

Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency

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

Antenatal

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)

Classic 21-OHD CAH

Summary

Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency (classic 21-OHD CAH) affects the adrenal glands which are responsible for producing specific hormones. There are two types of classic 21-OHD CAH, the salt-wasting form and the simple-virilizing form. Symptoms include abnormal development of the external sex organs in females (ambiguous genitalia), early puberty, and short stature. The salt-wasting form also may include the inability to retain salt and water. This can lead to dehydration, low blood pressure, and a life-threatening adrenal crisis. Classic 21-OHD CAH is caused by a genetic pathogenic variant in the CYP21A2 gene and is inherited in an autosomal recessive pattern. Diagnosis is based on the symptoms, blood hormone testing and may be confirmed by the results of genetic testing. Classic 21-OHD CAH can be diagnosed through a newborn screen. Treatment can prevent the more severe symptoms and may involve hormone replacement. in addition, some girls with abnormal genitalia may be offered surgery.[1][2][3][4]

Symptoms

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 hair growth rate
Abnormality of pace of hair growth
Abnormality of speed of hair growth

[ more ]

0011363
Accelerated bone age after puberty
0002805
Acidosis
0001941
Adrenogenital syndrome
0000840
Congenital adrenal hyperplasia
0008258
Decreased circulating aldosterone level
Low blood aldosterone level
0004319
Decreased circulating cortisol level
Low blood cortisol level
0008163
Dehydration
0001944
Elevated circulating follicle stimulating hormone level
0008232
Elevated circulating luteinizing hormone level
0011969
Enlarged polycystic ovaries
Enlarged ovaries with cysts
0008675
Feeding difficulties
Feeding problems
Poor feeding

[ more ]

0011968
Hirsutism
Excessive hairiness
0001007
Hyperkalemia
Elevated serum potassium levels
0002153
Hypernatriuria
0012605
Hyponatremia
Low blood sodium levels
0002902
Hypotension
Low blood pressure
0002615
Hypovolemia
Depleted blood volume
0011106
Increased circulating ACTH level
High blood corticotropin levels
0003154
Increased circulating androgen level
0030348
Increased circulating renin level
Elevated blood renin level
0000848
Irregular menstruation
Menstrual irregularity
0000858
Neonatal hypoglycemia
Low blood sugar in newborn
0001998
Osteoporosis
0000939
Premature adrenarche
0012412
Short stature
Decreased body height
Small stature

[ more ]

0004322
Vomiting
Throwing up
0002013
30%-79% of people have these symptoms
Abnormal oral glucose tolerance
0004924
Abnormal scrotal rugation
0012856
Abnormal spermatogenesis
0008669
Abnormality of circulating leptin level
0004361
Acne
0001061
Adrenocorticotropic hormone excess
0011749
Ambiguous genitalia, female
Atypical appearance of female genitals
0000061
Aortic root aneurysm
Bulge in wall of root of large artery that carries blood away from heart
0002616
Clitoral hypertrophy
Enlarged clitoris
0008665
Decreased fertility in females
Reduced fertility in females
0000868
Decreased fertility in males
0012041
Female sexual dysfunction
0030014
Fused labia minora
Fused inner lips
0000063
Generalized hyperpigmentation
0007440
Hyperpigmented genitalia
Increased genital pigmentation
0030258
Hypertension
0000822
Long penis
Enlarged penis
0000040
Obesity
Having too much body fat
0001513
Urogenital sinus anomaly
0100779
5%-29% of people have these symptoms
Adrenal medullary hypoplasia
0008239
Adrenocortical adenoma
0008256
Aggressive behavior
Aggression
Aggressive behaviour
Aggressiveness

[ more ]

0000718
Ectopic adrenal gland
Abnormal adrenal gland position
0011742
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Female pseudohermaphroditism
0010458
Gynecomastia
Enlarged male breast
0000771
Insulin resistance
Body fails to respond to insulin
0000855
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Maternal virilization in pregnancy
0008072
Renal salt wasting
Loss of salt in urine
0000127

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Newborn Screening

  • 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.

    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.

      In-Depth Information

      • 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.
      • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.

        References

        1. Congenital Adrenal Hyperplasia. National Organization of Rare Disorders (NORD). Updated 2018; . https://rarediseases.org/rare-diseases/congenital-adrenal-hyperplasia/.
        2. Nimkarn A, Gangishetti PK, Yau M, New MI. 21-Hydroxylase-Deficient Congenital Adrenal Hyperplasia. GeneReviews. Updated Feb 4, 2016; https://www.ncbi.nlm.nih.gov/books/NBK1171/.
        3. New M, Yau M, Lekarev O, Lin-Su K, Parsa A, Pina C, et al. Congenital Adrenal Hyperplasa. In: Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000–. Updated Mar 15, 2017; https://pubmed.ncbi.nlm.nih.gov/25905188/.
        4. Merke DP. Genetics and clinical presentation of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency. UpToDate. Updated Feb 28, 2020; https://www.uptodate.com/contents/genetics-and-clinical-presentation-of-classic-congenital-adrenal-hyperplasia-due-to-21-hydroxylase-deficiency.