National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

X-linked adrenal hypoplasia congenita


Other Names:
X-linked congenital adrenal hypoplasia; X-linked AHC; Adrenal hypoplasia congenita; X-linked congenital adrenal hypoplasia; X-linked AHC; Adrenal hypoplasia congenita; Congenital adrenal hypoplasia See More
Categories:
X-linked adrenal hypoplasia congenita is an inherited disorder that mainly affects males. It involves many hormone-producing (endocrine) tissues in the body, particularly a pair of small glands on top of each kidney called the adrenal glands. These glands produce a variety of hormones that regulate many essential functions in the body. Congenital adrenal hypoplasia is characterized by adrenal insufficiency, which may be life threatening, and hypogonadotropic hypogonadism. Congenital adrenal hypoplasia is caused by mutations in the NR0B1 gene. It is inherited in an X-linked recessive pattern.[1]
Last updated: 8/15/2012
X-linked adrenal hypoplasia congenita is a disorder that mainly affects males. One of the main signs of this disorder is adrenal insufficiency, which occurs when the adrenal glands do not produce enough hormones. Adrenal insufficiency typically begins in infancy or childhood and can cause vomiting, difficulty with feeding, dehydration, extremely low blood sugar (hypoglycemia), and shock. If untreated, these complications may be life-threatening.[1]

Affected males may also have a shortage of male sex hormones, which leads to underdeveloped reproductive tissues, undescended testicles, delayed puberty, and an inability to father children. Together, these characteristics are known as hypogonadotropic hypogonadism.[1]

The onset and severity of these signs and symptoms can vary, even among affected members of the same family.[1]

Last updated: 8/15/2012

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.

Showing of 18 |
Medical Terms Other Names
Learn More:
HPO ID
Percent of people who have these symptoms is not available through HPO
Absence of pubertal development 0008197
Adrenal hypoplasia
Small adrenal glands
0000835
Autosomal recessive inheritance 0000007
Azoospermia
Absent sperm in semen
0000027
Cryptorchidism
Undescended testes
Undescended testis
[ more ] 		0000028
Decreased circulating aldosterone level
Low blood aldosterone level
0004319
Decreased circulating cortisol level
Low blood cortisol level
0008163
Dehydration 0001944
Delayed puberty
Delayed pubertal development
Delayed pubertal growth
Pubertal delay
[ more ] 		0000823
Failure to thrive
Faltering weight
Weight faltering
[ more ] 		0001508
Hyperpigmentation of the skin
Patchy darkened skin
0000953
Hypogonadotropic hypogonadism 0000044
Hyponatremia
Low blood sodium levels
0002902
Muscular dystrophy 0003560
Oligospermia
Low sperm count
0000798
Precocious puberty
Early onset of puberty
Early puberty
[ more ] 		0000826
Renal salt wasting
Loss of salt in urine
0000127
X-linked recessive inheritance 0001419
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Last updated: 7/1/2020
X-linked adrenal hypoplasia congenita is caused by mutations in the NR0B1 gene. The NR0B1 gene provides instructions to make a protein called DAX1. This protein plays an important role in the development and function of several hormone-producing tissues including the adrenal glands, two hormone-secreting glands in the brain (the hypothalamus and pituitary), and the gonads (ovaries in females and testes in males). The hormones produced by these glands control many important body functions.[1]

Some NR0B1 mutations result in the production of an inactive version of the DAX1 protein, while other mutations delete the entire gene. The resulting shortage of DAX1 disrupts the normal development and function of hormone-producing tissues in the body. The signs and symptoms of adrenal insufficiency and hypogonadotropic hypogonadism occur when endocrine glands do not produce the right amounts of certain hormones.[1]

Last updated: 8/15/2012
X-linked adrenal hypoplasia congenita is inherited in an X-linked recessive pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation must be present in both copies of the gene to cause the disorder. Males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.[1]

In X-linked recessive inheritance, a female with one mutated copy of the gene in each cell is called a carrier. She can pass on the altered gene, but usually does not experience signs and symptoms of the disorder. In rare cases, however, females who carry a NR0B1 mutation may experience adrenal insufficiency or signs of hypogonadotropic hypogonadism such as underdeveloped reproductive tissues, delayed puberty, and an absence of menstruation.[1]

Last updated: 8/15/2012

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

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 related to X-linked adrenal hypoplasia congenita. 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.

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

  • Genetics Home Reference (GHR) contains information on X-linked adrenal hypoplasia congenita. This website is maintained by the National Library of Medicine.

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.
  • 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. 
  • 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 X-linked adrenal hypoplasia congenita. Click on the link to view a sample search on this topic.

Selected Full-Text Journal Articles

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  1. X-linked adrenal hypoplasia congenita. Genetics Home Reference (GHR). 2008; http://ghr.nlm.nih.gov/condition/x-linked-adrenal-hypoplasia-congenita. Accessed 8/15/2012.