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X-linked adrenal hypoplasia congenita

Reviewed April 2008

What is X-linked adrenal hypoplasia congenita?

X-linked adrenal hypoplasia congenita is a 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.

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 are often life-threatening.

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

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

How common is X-linked adrenal hypoplasia congenita?

X-linked adrenal hypoplasia congenita is estimated to affect 1 in 12,500 newborns.

What genes are related to X-linked adrenal hypoplasia congenita?

Mutations in the NR0B1 gene cause X-linked adrenal hypoplasia congenita. 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 (endocrine) 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.

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.

How do people inherit X-linked adrenal hypoplasia congenita?

This condition 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 striking characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

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.

Where can I find information about treatment for X-linked adrenal hypoplasia congenita?

You may find information on treatment or management of X-linked adrenal hypoplasia congenita or some of its symptoms in the links below, particularly the links for Gene Reviews, MedlinePlus Encyclopedia, Educational resources, and Patient support.

Where can I find additional information about X-linked adrenal hypoplasia congenita?

You may find the following resources about X-linked adrenal hypoplasia congenita helpful. These materials are written for the general public.

  • MedlinePlus - Health information
    • Encyclopedia: Adrenal Glands (http://www.nlm.nih.gov/medlineplus/ency/article/002219.htm)
    • Encyclopedia: Hypogonadotropic Hypogonadism (http://www.nlm.nih.gov/medlineplus/ency/article/000390.htm)
    • Health Topic: Adrenal Gland Disorders (http://www.nlm.nih.gov/medlineplus/adrenalglanddisorders.html)
    • Health Topic: Endocrine Diseases (http://www.nlm.nih.gov/medlineplus/endocrinediseases.html)
  • Additional NIH Resources - National Institutes of Health
    • NIH Clinical Center: Managing Adrenal Insufficiency (http://www.cc.nih.gov/ccc/patient_education/pepubs/mngadrins.pdf)
  • Educational resources - Information pages
    • New York Online Access to Health: Adrenal Gland Disorders (http://www.noah-health.org/en/endocrine/adrenal/)
    • Orphanet (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=95349)
    • The Stanford Health Library: Adrenal Disorders (http://healthlibrary.stanford.edu/resources/bodysystems/endocrine_adrenal.html#adrenal)
  • Patient support - For patients and families
    • Family Village (http://www.familyvillage.wisc.edu/lib_adnd.htm)
    • National Adrenal Diseases Foundation (http://www.nadf.us/)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

  • Gene Reviews - Clinical summary
    • Gene Review: Hypogonadotropic Hypogonadism Overview (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=ihh-ov)
    • Gene Review: X-Linked Adrenal Hypoplasia Congenita (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=ahc)
  • Gene Tests - DNA tests ordered by healthcare professionals (http://www.genetests.org/query?testid=192605)
  • ClinicalTrials.gov - Linking patients to medical research (http://clinicaltrials.gov/search/condition=%22X-linked+adrenal+hypoplasia+congenita%22)
  • PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=PubMed&term=((x-linked+adrenal+hypoplasia+congenita[TIAB])+OR+(congenital+adrenal+hypoplasia[TIAB]))+OR+((x-linked+ahc[TIAB])+OR+(adrenal+hypoplasia+congenita[TIAB]))+AND+english[la]+AND+human[mh]&orig_db=PubMed&filters=ON&pmfilter_EDatLimit=1080+Days)
  • Online Books - Medical and science texts
    Scriver's Online Metabolic and Molecular Bases of Inherited Disease (OMMBID): Adrenal Hypoplasias and Aplasias (http://books.mcgraw-hill.com/getommbid.php?isbn=0071459960&template=ommbid&c=167)
  • OMIM - Genetic disorder catalog (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300200)

What other names do people use for X-linked adrenal hypoplasia congenita?

  • Adrenal hypoplasia congenita
  • X-linked AHC

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about X-linked adrenal hypoplasia congenita?

  • See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.
  • Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).
  • Submit your question to Ask the Geneticist (http://www.askthegen.org/).

What glossary definitions help with understanding X-linked adrenal hypoplasia congenita?

adrenal cortex ; adrenal glands ; carrier ; cell ; chromosome ; complication ; cryptorchidism ; dehydration ; endocrine gland ; gene ; gonad ; hormone ; hypoglycemia ; hypogonadism ; hypogonadotropic ; hypoplasia ; hypothalamus ; infertility ; inheritance ; kidney ; menstruation ; mutation ; ovary ; protein ; puberty ; recessive ; sex chromosomes ; sex hormone ; shock ; sign ; symptom ; testes ; testicles ; tissue ; trait ; undescended testicle ; wasting ; X-linked recessive

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

References
  • Ahmad I, Paterson WF, Lin L, Adlard P, Duncan P, Tolmie J, Achermann JC, Donaldson MD. A novel missense mutation in DAX-1 with an unusual presentation of X-linked adrenal hypoplasia congenita. Horm Res. 2007;68(1):32-7. Epub 2007 Feb 16. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=17308433)
  • Clipsham R, McCabe ER. DAX1 and its network partners: exploring complexity in development. Mol Genet Metab. 2003 Sep-Oct;80(1-2):81-120. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=14567960)
  • Fujieda K, Okuhara K, Abe S, Tajima T, Mukai T, Nakae J. Molecular pathogenesis of lipoid adrenal hyperplasia and adrenal hypoplasia congenita. J Steroid Biochem Mol Biol. 2003 Jun;85(2-5):483-9. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=12943739)
  • Fujieda K, Tajima T. Molecular basis of adrenal insufficiency. Pediatr Res. 2005 May;57(5 Pt 2):62R-69R. Epub 2005 Apr 6. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=15817507)
  • Gene Review: X-Linked Adrenal Hypoplasia Congenita (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=ahc)
  • Hammer GD, Parker KL, Schimmer BP. Minireview: transcriptional regulation of adrenocortical development. Endocrinology. 2005 Mar;146(3):1018-24. Epub 2004 Dec 16. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=15604207)
  • Lalli E, Sassone-Corsi P. DAX-1, an unusual orphan receptor at the crossroads of steroidogenic function and sexual differentiation. Mol Endocrinol. 2003 Aug;17(8):1445-53. Epub 2003 May 29. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=12775766)
  • Ludbrook LM, Harley VR. Sex determination: a 'window' of DAX1 activity. Trends Endocrinol Metab. 2004 Apr;15(3):116-21. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=15046740)
  • Mantovani G, De Menis E, Borretta G, Radetti G, Bondioni S, Spada A, Persani L, Beck-Peccoz P. DAX1 and X-linked adrenal hypoplasia congenita: clinical and molecular analysis in five patients. Eur J Endocrinol. 2006 May;154(5):685-9. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=16645015)
  • Sehgal A, Stack J. Complex glycerol kinase deficiency: An X-linked disorder associated with adrenal hypoplasia congenita. Indian J Pediatr. 2005 Jan;72(1):67-9. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=15684452)
  • Tabarin A. Congenital adrenal hypoplasia and DAX-1 gene mutations. Ann Endocrinol (Paris). 2001 Apr;62(2):202-6. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=11353895)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: April 2008
Published: May 4, 2009