21-hydroxylase deficiency

Title

Other Names:

Congenital adrenal hyperplasia due to 21-hydroxylase deficiency; CYP21 deficiency; 21 hydroxylase deficiency; Congenital adrenal hyperplasia due to 21-hydroxylase deficiency; CYP21 deficiency; 21 hydroxylase deficiency; Adrenal hyperplasia, congenital, due to 21-hydroxylase deficiency See More

Categories:

Newborn Screening

Summary Summary

21-hydroxylase-deficiency is a genetic disorder of cortisol biosynthesis. It is caused by mutations in the human 21-hydroxylase gene (CYP21A2).^[1] Symptoms of 21-hydroxylase deficiency vary, but can involve salt-wasting crises in infants; ambiguous genitalia in female infants; excessive hair, deep voice, abnormal periods, no periods, and fertility problems in older girls and women; early development of masculine features in boys; and shorter than average adult height, acne, and blood pressure problems.^[2]

Last updated: 2/22/2010

Symptoms Symptoms

Symptoms can vary greatly from patient to patient with 21-hydroxylase deficiency, as a result distinct forms of this deficiency have been recognized. Three common forms include classical salt wasting, simple virilizing, and nonclassical.^[1]

Last updated: 7/25/2013

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Abnormality of the thorax	-
Adrenal hyperplasia	-
Adrenogenital syndrome	-
Autosomal recessive inheritance	-
Fever	-
Growth abnormality	-
Gynecomastia	-
Hypertension	-
Hypoglycemia	-
Hypospadias	-
Renal salt wasting	-

Last updated: 9/1/2017

The classical salt wasting form of 21-hydroxylase-deficient is a severe form of 21-hydroxylase deficiency. People with this condition have no 21-hydroxylase function.Within the first week of life newborns may have life threatening salt-wasting crises and low blood pressure. Females are often born with ambiguous genitalia.^[1]

A close look at the hormone levels in patients with this form of 21-hydroxylase deficiency reveals an increased level of testosterone and rennin, and reduced levels of cortisol and aldosterone. Levels of 17-hydroxyprogesterone is over 5,000 nmol/L.^[1]

Last updated: 7/25/2013

Patients with simple virilizing 21-hydroxylase-deficient congenital adrenal hyperplasia have some functioning 21-hydroxylase (about 1%). Females may be born with clitoral enlargement, labial fusion, and sexual ambiguity. Males may present in early childhood with signs of precocious puberty such as very early sexual development, pubic hair development, and/or growth acceleration. Untreated patients have a shorter than average adult height.^[1]

A close look at hormone levels in patients with simple virilizing 21-hydroxylase deficiency reveal an increased level of testosterone, reduced level of cortisol, normal or increased level of renin, and normal levels of aldosterone. Levels of 17-Hydroxyprogesterone are 2500 to 5000 nmol/L.^[1]

Last updated: 7/25/2013

People with nonclassical or late-onset 21-hydroxylase-deficient congenital adrenal hyperplasia have 20% to 50% of 21-Hydroxylase activity. They may present in childhood or adulthood with early pubic hair growth or with symptoms of polycystic ovary syndrome. In females symptoms may include excessive hair growth, absent periods, infertility, androgenic alopecia, masculinized genitalia, and acne.^[1] Height is likely to be normal.

A close look at the hormone levels in patients with the nonclassical type reveal a variably increased level of testosterone and normal levels of aldosterone, renin, and cortisol. Levels of 17-Hydroxyprogesterone are 500 to 2500 nmol/L.^[1]

Last updated: 7/25/2013

Cause Cause

Salt-wasting, simple virilizing, and late-onset 21-hydroxylase deficiency are all caused by mutations in the human 21-hydroxylase gene (CYP21A2).

Last updated: 7/25/2013

Inheritance Inheritance

21-hydroxylase-deficient congenital adrenal hyperplasia has an autosomal recessive pattern of inheritance. In autosomal recessive conditions, both parents carry one copy of a mutated gene for the disorder. They have a 25 percent chance with each pregnancy of having a child affected by the disorder. The chance with each pregnancy of having an unaffected child who is a carrier of the disorder is 50 percent, and the chance that a child will not have the disorder and will not be a carrier is 25 percent. See the illustration below.^[3]

In this example, two unaffected parents each carry one copy of a gene mutation for an autosomal recessive disorder. They have one affected child and three unaffected children, two of which carry one copy of the gene mutation.

In this example, two unaffected parents each carry one copy of a gene mutation for an autosomal recessive disorder. They have one affected child and three unaffected children, two of which carry one copy of the gene mutation.

Last updated: 7/25/2013

Diagnosis Diagnosis

Yes. Genetic testing of 21-hydroxylase-deficient congenital adrenal hyperplasia is available. In most people with this condition, the genetic test result can be used to predict disease severity.^[4] Click here to view a list of laboratories offering CYP21A2 testing.

Last updated: 7/25/2013

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.
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 below to view details for the three types of congenital adrenal hyperplasia due to 21-hydroxylase.
Congenital adrenal hyperplasia (non-classical)
Congenital adrenal hyperplasia (salt-wasting)
Congenital adrenal hyperplasia (simple virilizing)

Treatment Treatment

The objectives for treating 21-hydroxylase deficiency differ with age. In childhood, the overall goal is to replace cortisol. Obtaining hormonal balance is important and patient’s growth velocity and bone age is monitored. Routine analysis of blood, urine, and/or saliva may also be necessary. Corrective surgery is frequently required for females born with abnormal genitalia.^[1]

In late childhood and adolescence, maintaining hormonal balance is equally important. Overtreatment may result in obesity and delayed menarche/puberty, whereas under-replacement will result in sexual precocity. Also, it is important that teens and young adults with 21-hydroxylase deficiency be successfully transitioned to adult care facilities.^[1]

Follow-up of adult patients should involve multidisciplinary clinics. Problems in adult women include fertility concerns, excessive hair growth, and menstrual irregularity; obesity and impact of short stature; sexual dysfunction and psychological problems. Counseling may be helpful. Adult males may develop enlargement of the testes and if so, should work with an endocrinologist familiar with the management of patients with this deficiency.^[1]

Last updated: 7/25/2013

Management Guidelines

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.

Do you have updated information on this condition? Let us know.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

ClinicalTrials.gov lists trials that are studying or have studied 21-hydroxylase deficiency. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Organizations 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

Congenital Adrenal Hyperplasia Research Education and Support (CARES) Foundation
2414 Morris Ave, Suite 110
Union, NJ 07083
Toll-free: 866-227-3737
E-mail: contact@caresfoundation.org
Website: http://www.caresfoundation.org

Do you know of an organization? Send us your suggestions.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Genetics Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by GeneTests, the American College of Medical Genetics, and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Learn More 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

The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) provides information related to the health of children, adults, and families. Click on the link to view information on this topic.
The Genetic Alliance is an international coalition comprised of more than 600 advocacy, research and health care organizations representing millions of individuals with genetic conditions. Click on the link to view information on this topic.
Genetics Home Reference (GHR) contains information on 21-hydroxylase deficiency. This website is maintained by the National Library of Medicine.
The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

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.
PubMed is a searchable database of medical literature and lists journal articles that discuss 21-hydroxylase deficiency. Click on the link to view a sample search on this topic.

News & Events News & Events

News

Don’t Miss the NCATS Toolkit for Patient-Focused Therapy Development Event
August 31, 2017
Funding Opportunities Now Available for the Undiagnosed Diseases Network (UDN) Phase II
August 30, 2017
IRDiRC Goals 2017-2027: New Rare Disease Research Goals for the Next Decade
August 10, 2017

NCATS Co-Sponsored Conferences

International Adrenal Cortex Conference “Adrenal 2010” Wednesday, June 16, 2010 - Friday, June 18, 2010
Location: San Diego, California
Description: This conference provided a forum for both new and established investigators to present their most recent work, highlighting new findings relevant to adrenal physiology, biochemistry and molecular biology, genetics, and medicine. It was anticipated that these discoveries would provide a framework for further understanding of the function of the adrenal gland and its contributions to health and disease.

Contact: Maria L. Dufau, M.D., Ph.D., dufaum@mail.nih.gov dufaum@mail.nih.gov

Co-funding Institute(s): National Institute of Child Health and Human Development, Office of Rare Diseases Research
- Agenda ( - 53KB)
- Report ( - 71KB)

Related Diseases Related Diseases

The following diseases are related to 21-hydroxylase deficiency. If you have a question about any of these diseases, you can contact GARD.

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

My 1-month-old grandson was diagnosed with congenital adrenal hyperplasia, after an abnormal newborn screening result. We were told his condition is due to 21-hydroxylase deficiency and possibly also 17-hydroxyprogesterone. Do you have information on this condition that I could share with my family? See answer

Have a question? Contact a GARD Information Specialist.

References References

Stewart PM. The adrenal cortex. In: Kronenberg HM, Melmed S, Polonsky KS, Larsen PR, eds. Kronenberg: Williams Textbook of Endocrinology. 11th ed. Philadelphia, PA: Saunders; 2008..
Congenital Adrenal Hyperplasia: What It Is and How It's Treated. American Academy of Family Physicians. 2006; http://familydoctor.org/familydoctor/en/diseases-conditions/congenital-adrenal-hyperplasia/treatment.html. Accessed 4/4/2008.
If a genetic disorder runs in my family, what are the chances that my children will have the condition?. Genetics Home Reference. http://ghr.nlm.nih.gov/handbook/inheritance/riskassessment. Accessed 4/4/2008.
New MI, Nimkarn SJ. 21-Hydroxylase-Deficient Congenital Adrenal Hyperplasia . GeneReviews. 2006; http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=cah. Accessed 4/4/2008.