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Genetic and Rare Diseases Information Center (GARD)

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21-hydroxylase deficiency


Other Names for this Disease

  • 21 hydroxylase deficiency
  • Congenital adrenal hyperplasia due to 21-hydroxylase deficiency
  • CYP21 deficiency
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.

Your 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?

Our Answer

We have identified the following information that we hope you find helpful. If you still have questions, please contact us.

What is 21-hydroxylase-deficiency?

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

What is 21-hydroxylase?

21-hydroxylase is a steroid. It enables the adrenal glands, which are located on top of the kidneys, to convert cholesterol into other steroid hormones, specifically cortisol and aldosterone. Cortisol helps maintain blood sugar levels, protects the body from stress, and suppresses inflammation. Aldosterone, sometimes called the salt-retaining hormone, acts on the kidneys to regulate the levels of salt and water in the body, which affect blood pressure. Precursor molecules that are formed in the pathway leading to these two steroid hormones can be converted into male hormones called androgens. Androgens are normally responsible for the appearance of secondary sex characteristics in males (virilization).[3]
Last updated: 7/25/2013

What is 17α-hydroxyprogesterone?

17α-hydroxyprogesterone is a hormone involved in the production of cortisol. In 21-hydroxylase-deficient congenital adrenal hyperplasia, cortisol production is defective because the body is not able to convert 17α-hydroxyprogesterone to 11-deoxycortisol.[1]
Last updated: 7/25/2013

What are the symptoms of 21-hydroxylase-deficient congenital adrenal hyperplasia?

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

What are the symptoms of classical salt wasting 21-hydroxylase-deficient congenital adrenal hyperplasia?

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

What are the symptoms of simple virilizing 21-hydroxylase-deficient congenital adrenal hyperplasia?

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

What are the symptoms of nonclassical 21-hydroxylase-deficient congenital adrenal hyperplasia?

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

What causes salt-wasting, simple virilizing, and nonclassical 21-hydroxylase-deficient congenital adrenal hyperplasia?

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

How is 21-hydroxylase-deficient congenital adrenal hyperplasia passed through families?

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.[4]

                                            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

Is genetic testing for 21-hydroxylase-deficient congenital adrenal hyperplasia available?

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.[5] Click here to view a list of laboratories offering CYP21A2 testing.
Last updated: 7/25/2013

What is the goal for treating 21-hydroxylase-deficient congenital adrenal hyperplasia?

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

References
Other Names for this Disease
  • 21 hydroxylase deficiency
  • Congenital adrenal hyperplasia due to 21-hydroxylase deficiency
  • CYP21 deficiency
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.