Adrenal Hypoplasia Congenital (X-linked)

Definition

Definition of Adrenal Hypoplasia Congenital (X-linked)
X-linked adrenal hypoplasia congenita genetic disorder where it involves the endocrine tissues particularly the adrenal glands. It is usually manifests by adrenal insufficiency where there is reduction of the adrenal gland function which causes incomplete development of the adrenal cortex or the outer layer of the gland. It usually affects male thus, the symptoms includes manifestation of hypogonadotropic hypogonadism which are shown through the less and even lack of sex hormones which causes undeveloped reproductive tissues and cyptorchidism or the undescended testicles and infertility. In women, this disorder is rare but symptoms includes insufficiency of sex hormones and amenorrhea or lack of mentruation. It is said to be caused by the mutation and deletion of the NRRoB1 located at the X chromosome Xp21.3-p21.3 which are responsible for giving DAX1 or the transcription factor protein which controls the activity of certain genes.

Symptoms

Symptoms of Adrenal Hypoplasia Congenital (X-linked)
One of the main characteristics of this disorder is adrenal insufficiency, which is a reduction in adrenal gland function resulting from incomplete development of the gland's outer layer (the adrenal cortex). Adrenal insufficiency typically begins in infancy or in childhood and can cause vomiting, difficulty with feeding, dehydration, extremely low blood sugar (hypoglycemia), low sodium levels, and shock. However, adult-onset cases have also been described. See also Addison's Disease.

Causes

Causes of Adrenal Hypoplasia Congenital (X-linked)
Mutations in the NR0B1 gene located on the X chromosome (Xp21.3-p21.2) cause X-linked adrenal hypoplasia congenita. The NR0B1 gene provides instructions to make a transcription factor protein called DAX1 that helps control the activity of certain genes. When the NR0B1 gene is deleted or mutated, the activity of certain genes is not properly controlled. This leads to problems with the development of the adrenal glands, two structures in the brain (the hypothalamus and pituitary gland), and reproductive tissues (the ovaries or testes). These tissues are important for the production of many hormones that control various functions in the body. When these hormones are not present in the correct amounts, the signs and symptoms of adrenal insufficiency and hypogonadotropic hypogonadism can result. This condition is inherited in an X-linked recessive pattern.

Diagnosis

Diagnosis of Adrenal Hypoplasia Congenital (X-linked)
Primary adrenal failure characterized by hyponatremia, hyperkalemia, acidosis, and an elevated serum concentration of ACTH in the presence of normal or low serum concentration of 17-hydroxyprogesterone presenting in a male in the first month of life strongly suggests X-linked AHC. Males with such findings may have: 1) a contiguous gene deletion including the glycerol kinase gene (GK) with or without deletion of DMD, the gene encoding dystrophin (~1/3 of all affected individuals); 2) isolated AHC with a positive family history consistent with X-linked inheritance (~1/3 of affected individuals); or 3) isolated AHC with a negative family history (~1/3 of affected individuals). Individuals with a contiguous gene deletion can be identified by fluorescent in situ hybridization (FISH) using a NR0B1 (DAX1) cosmid probe or other deletion/duplication testing methods. Such testing is clinically available. Nearly 100% of affected individuals with a positive family history consistent with X-linked inheritance have an identifiable mutation in NR0B1, the only gene associated with X-linked adrenal hypoplasia congenita. Between 50% and 70% of males with AHC who have no other affected family members have an identifiable mutation in NR0B1. Molecular genetic testing of the NR0B1 gene is clinically available.

Treatment

Treatment of Adrenal Hypoplasia Congenital (X-linked)
Episodes of acute adrenal insufficiency usually require admission to an intensive care unit with close monitoring of blood pressure, hydration, clinical status, and serum concentration of glucose and electrolytes. Treatment includes the IV administration of saline, glucose, and cortisol. Follow-up includes replacement doses of glucocorticoids and mineralocorticoids and oral supplements of sodium chloride (NaCl), which must be increased during periods of stress. Steroid replacement therapy must be monitored by an endocrinologist. Affected individuals with hypogonadotropic hypogonadism may need increasing doses of testosterone to induce puberty. Surveillance includes monitoring of serum concentration of LH and FSH if puberty has not started by age 14 years. Stress should be avoided.

Prognosis

Prognosis of Adrenal Hypoplasia Congenital (X-linked)
Consult with your doctor.

Prevention

Prevention of Adrenal Hypoplasia Congenital (X-linked)
Consult with your doctor.