What does a positive newborn screening result for 21-hydroxylase deficiency mean?

A positive newborn screening result for 21-hydroxylase deficiency indicates that your baby may have a genetic disorder affecting the adrenal glands, which are glands located above the kidneys that produce essential hormones. This disorder is a form of Congenital Adrenal Hyperplasia (CAH) and results in the adrenal glands producing excess male hormones (androgens) and lacking important hormones such as cortisol and aldosterone [3].

It is very important to follow up on this result quickly with additional testing to confirm the diagnosis. If these conditions are not treated, they can cause serious and long-term health problems, or even early death [1].

Understanding 21-Hydroxylase Deficiency

21-hydroxylase deficiency is a genetic disorder that affects the adrenal glands and is the most common cause of Congenital Adrenal Hyperplasia, accounting for about 95% of cases [3]. This disorder is caused by mutations in the CYP21A2 gene, which provides instructions for producing the 21-hydroxylase enzyme. This enzyme is essential for the production of the hormones cortisol and aldosterone [3].

Cortisol has multiple functions, such as regulating blood sugar levels and protecting the body from stress. Aldosterone regulates the amount of salt the kidneys retain, which affects fluid levels and blood pressure. When 21-hydroxylase is deficient, the substances typically used to make cortisol and aldosterone accumulate and are converted into excess androgens, leading to problems with sexual development [3].

Types of 21-Hydroxylase Deficiency

There are three main types of 21-hydroxylase deficiency, which vary in severity:

• Classic (Salt-wasting) type: This is the most severe type, leading to the loss of large amounts of sodium in the urine, which can be life-threatening in early infancy. Infants with this type may suffer from poor feeding, weight loss, dehydration, and vomiting [3].
• Classic (Simple virilizing) type: This type is less severe than the salt-wasting type and does not cause salt loss. In both classic types, females may have external genitalia that do not clearly appear male or female [3].
• Non-classic type: This is the least severe type, and some affected individuals may not show any symptoms. Females with this type may experience excessive body hair growth, male-pattern baldness, irregular menstrual periods, and reduced fertility as they age [3].

Next Steps After a Positive Result

If you receive notification that your baby's newborn screening showed a positive result for 21-hydroxylase deficiency, it is essential to act quickly. Your healthcare provider or the health department will contact you to guide you on the next steps [1]. These steps usually include:

• Confirmatory testing: Your baby will need additional tests, such as blood tests, to confirm whether they have the disease. These tests are essential to determine the accurate diagnosis [1].
• Medical consultation: You will be referred to a pediatric endocrinologist to evaluate your baby's condition and develop an appropriate treatment plan if the diagnosis is confirmed.
• Starting early treatment: If the diagnosis is confirmed, treatment should begin immediately. Early diagnosis and treatment can prevent serious or permanent health problems [1]. For example, children who are diagnosed and treated early can live longer, healthier lives [2].

The Importance of Early Diagnosis and Treatment

Early diagnosis of 21-hydroxylase deficiency is vital because treatment can begin before serious problems appear or become permanent [1]. Without treatment, 21-hydroxylase deficiency can lead to life-threatening complications, especially in the salt-wasting type [3]. Thanks to newborn screening programs, these rare conditions can be detected and immediate treatment started, allowing children to grow normally and reach adulthood in good health [2]. For more information on the importance of newborn screenings in general, you can visit Newborn screenings: Early detection of genetic and infectious diseases (Arabic).

Medical references

• Newborn Screening
• 21-hydroxylase deficiency: MedlinePlus Genetics
• What disorders are newborns screened for in the United States?