X-linked adrenal hypoplasia congenita

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What is X-Linked Adrenal Hypoplasia Congenita?

X-linked adrenal hypoplasia congenita (XLAHC) is a condition caused by harmful genetic changes (mutations) in the NR0B1 gene and primarily affects males. NR0B1 is an important for the development of organs that are important to producing hormones. This includes parts of the brain, the glands located above each kidney (adrenal glands), the ovaries, and the testes. When these organs are unable to properly produce hormones, the body cannot retain enough salt and lacks important sex hormones for development. An inability to retain salt is commonly called "salt wasting" and leads to serious side effects, such as dehydration, vomiting, diarrhea, failure to thrive, heart rhythm abnormalities (arrhythmias), and shock. If not recognized and properly treated, a salt-wasting crisis can be fatal. Lack of sex hormones produced by the adrenal glands is called hypogonadotropic hypogonadism. The lack of sex hormones can cause males with XLAHC to have smaller than average sex organs, undescended testes, delayed or incomplete puberty, and fertility problems.

Most commonly, affected males will show signs of the disease from the first few weeks of life to early childhood, but some later-onset cases have been reported. The age of onset and severity of symptoms can be variable, even within the same family.

XLAHC is an X-linked disease which means that the NR0B1 gene is on the X chromosome. Males have one copy of the X chromosome and the NR0B1 gene, while females have two copies. Because of this, males with a mutation in NR0B1 are affected by XLAHC, while most female carriers still have one working copy of the gene. While most female carriers do not have symptoms, there are rare case reports of female carriers affected by adrenal insufficiency or hypogonadotropic hypogonadism.

How common is X-Linked Adrenal Hypoplasia Congenita?

Studies estimate that between 1 in 70,000 and 1 in 600,000 males will have XLAHC, but the true global incidence is unknown. Other presentations of XLAHC may not be recognized as of yet.

How is X-Linked Adrenal Hypoplasia Congenita treated?

Currently, there is no cure for XLAHC and treatments is based on symptoms. Patients will benefit from taking hormone replacement medications to restore and maintain the right balance of hormones in the body; most patients will need to take hormone medications for the rest of their lives. A multidisciplinary team of physicians, including an endocrinologist, will need to monitor the hormone levels to determine medication dosage, medication side effects, growth, and sexual development of patients with this condition. The endocrinologist will carefully monitor sex hormones near puberty and supplement hormones if puberty is delayed or not progressing as expected. Once the condition is diagnosed, illness caused by salt wasting should be treated in a hospital, where the imbalances can be monitored and corrected.

What is the prognosis for an individual with X-Linked Adrenal Hypoplasia Congenita?

With early diagnosis and proper medication management, most individuals with XLAHC will have a normal life expectancy. Early death can occur during periods of significant salt loss (salt crises), especially during times of illness or trauma. Problems with sexual development and infertility are monitored by physicians on an ongoing basis.