The MAGIC Foundation India CAH – Diagnosis

About 1 in 10,000 to 18,000 children are born with congenital adrenal hyperplasia (CAH). The most common cause of CAH, accounting for ~95% of all cases, is 21-hydroxylase deficiency (21HD). In the body 21-hydroxylase is created by a gene called CYP21A2. When this gene stops working properly not enough 21-hydroxylase is created. In south Asia, there are 6 main mutations in the CYP21A2 gene that cause CAH. These mutations may either make the gene work less efficiently or stop the gene from being made by the body at all. These latter mutations are more likely to lead to the more severe, salt wasting, form of the disease.

21HD is an autosomal recessive disease (see figure below). This means that both girls and boys have 2 copies of the gene and get the disease at approximately the same frequency. It also means you need to have both copies of this gene functioning improperly to get the disease. When you have one functioning copy and one non-functioning copy you will not have the disease but will be a “carrier” for CAH/21HD. In order to have a child with CAH, both parents must be carriers of the disease and the child must have gotten a bad copy of the gene from each parent. Most parents do not know they are carriers of the disease until they have a sick child as they show no outward signs of disease. Every child born to parental carriers has a 25% chance of getting the disease. If you have a child with CAH your other children will have a 50% chance of being a carrier for CAH and will be at increased risk of their own children developing CAH. Risk of having a child with CAH/21HD is increased if there is a family history of the disease, especially in families where cousins or other related individuals marry. Parents of a child with CAH should consider genetic testing for their unaffected children and should undergo genetic counselling to understand the risks of having more children.