X-linked congenital adrenal hypoplasia (XLCAH) is a condition that impacts the adrenal glands, found above the kidneys, causing them to not produce essential chemicals called hormones.
Without proper hormone production, the body struggles to retain enough sodium (salt), leading to a condition known as “salt wasting.” This can result in severe problems like dehydration, vomiting, diarrhea, failure to thrive, irregular heart rhythms, and shock. If not identified and treated correctly, a salt wasting crisis can be life-threatening. XLCAH can also affect the production of sex hormones by the adrenal glands, causing a condition called hypogonadotropic hypogonadism. In males with XLCAH, this shortage of sex hormones can result in smaller-than-average sex organs, undescended testes, delayed or incomplete puberty, and fertility issues. Most boys with XLCAH show signs of the disease from the first few weeks of life to early childhood, although some cases with later onset have been reported. The age of onset and symptom severity can vary, even within the same family. Currently, there is no cure for XLCAH, but there are treatments available to manage the symptoms.
XLCAH is caused by pathogenic (disease-causing) variants in the NR0B1 gene which exhibits X-linked recessive inheritance. This means that one pathogenic variant is enough to cause the disease in both males (who have one X chromosome and one Y chromosome) and females (who have two X chromosomes) may experience symptoms depending on how many copies of the X chromosome that has the pathogenic variant are turned on in the cells.
In most cases, female carriers do not experience symptoms, but there have been rare reports of female carriers with adrenal insufficiency or hypogonadotropic hypogonadism.
Other names for this condition are adrenal hypoplasia congenita and X-linked AHC.
Resources:
Genetic and Rare Diseases Center
Revised November 2023
