What are the other Names for this Condition? (Also known as/Synonyms)

• Adrenal Hypoplasia Congenita
• X-Linked AHC
• X-Linked Congenital Adrenal Hypoplasia

What is X-Linked Adrenal Hypoplasia Congenita? (Definition/Background Information)

• 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

(Source: X-Linked Adrenal Hypoplasia Congenita; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets X-Linked Adrenal Hypoplasia Congenita? (Age and Sex Distribution)

• X-Linked Adrenal Hypoplasia Congenita is a rare congenital disorder. The presentation of symptoms may occur at birth
• The disorder is mostly observed in males
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for X-Linked Adrenal Hypoplasia Congenita? (Predisposing Factors)

• A positive family history may be an important risk factor, since X-Linked Adrenal Hypoplasia Congenita can be inherited
• Currently, no other risk factors have been clearly identified for the disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of X-Linked Adrenal Hypoplasia Congenita? (Etiology)

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
• 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
• 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
• 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

(Source: X-Linked Adrenal Hypoplasia Congenita; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

What are the Signs and Symptoms of X-Linked Adrenal Hypoplasia Congenita?

The onset and severity of signs and symptoms of X-Linked Adrenal Hypoplasia Congenita can vary, even among affected members of the same family. The signs and symptoms may include:

• Absence of pubertal development
• Adrenal hypoplasia
• Azoospermia
• Cryptorchidism
• Decreased circulating aldosterone and cortisol level
• Dehydration
• Vomiting
• Hypoglycemia
• Delayed puberty
• Undescended testicles
• Hyperpigmentation of the skin
• Hypogonadotrophic hypogonadism
• Hyponatremia
• Muscular dystrophy
• Oligospermia
• Precocious puberty
• Renal salt-wasting

(Source: X-Linked Adrenal Hypoplasia Congenita; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is X-Linked Adrenal Hypoplasia Congenita Diagnosed?

X-Linked Adrenal Hypoplasia Congenita is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of X-Linked Adrenal Hypoplasia Congenita?

The complications of X-Linked Adrenal Hypoplasia Congenita may include:

• Failure to thrive
• Severe hypoglycemia can lead to shock
• Infertility
• Hormonal imbalances

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is X-Linked Adrenal Hypoplasia Congenita Treated?

There is no cure for X-Linked Adrenal Hypoplasia Congenita, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complications that develops.

How can X-Linked Adrenal Hypoplasia Congenita be Prevented?

X-Linked Adrenal Hypoplasia Congenita may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders
• Regular medical screening at periodic intervals with tests and physical examinations are recommended

What is the Prognosis of X-Linked Adrenal Hypoplasia Congenita? (Outcomes/Resolutions)

• The prognosis of X-Linked Adrenal Hypoplasia Congenita is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for X-Linked Adrenal Hypoplasia Congenita:

• X-Linked Adrenal Hypoplasia Congenita is also known as Congenital Adrenal Hypoplasia

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/