Just after birth, a few drops of blood are taken from a baby’s heel and placed on a card that is sent to the state’s newborn screening lab. The blood is screened for a variety of serious health conditions, including ALD. The ALD newborn screening test looks at levels of very long chain fatty acids (VLCFAs), which are elevated in all boys with ALD and 85% of girls with the ALD gene mutation. The results are then sent to the baby’s pediatrician and the hospital where they were born. Newborn screening is not considered a diagnostic test, meaning that additional testing, including biochemical tests and/or a DNA test (see FAQs), are needed after a positive newborn screen to confirm the diagnosis. In 2016, ALD was added to the Recommended Uniform Screening Panel (RUSP), meaning that Health and Human Services recommends all babies in the U.S. are screened for ALD. However, newborn screening for ALD has not yet been implemented in all states, and there are many countries outside the U.S. that do not screen for ALD. For up-to-date information on which states in the U.S. currently screen for ALD and advocacy efforts, see our “Advocate” page or visit the ALD Alliance website for more information.

Babies diagnosed with ALD through newborn screening are asymptomatic at birth. This means the individual has a mutation in the ABCD1 gene but does not have any symptoms. Boys with ALD often develop symptoms in childhood, including adrenal insufficiency and/or cerebral ALD. Or, they may be asymptomatic until adulthood, and develop symptoms associated with adrenomyeloneuropathy (AMN). Girls with ALD typically do not develop symptoms until later on in adulthood. Myeloneuropathy is common in women with ALD, while cerebral ALD and adrenal insufficiency are very rare in women.

There is currently no way to predict the way that an individual’s symptoms will change over time. ABCD1 pathogenic variants (i.e. the specific “spelling change” in the DNA sequence of the ABCD1 gene) have no predictive value with respect to the clinical outcome of an individual patient. Even brothers with the same genetic variant of the ABCD1 gene can have different symptoms. One brother may develop childhood cerebral ALD while the other remains asymptomatic until adulthood. Dr. Stephan Kemp, ALD Connect Board Member, manages the ALD Variant Database. His website, adrenoleukodystrophy.info provides excellent information about the ABCD1 gene and documented variants associated with ALD.

Sometimes, a baby diagnosed by newborn screening is identified to have an unique variant in the ABCD1 gene that has not been seen before in symptomatic ALD patients (i.e. a spelling change in the gene which has never been seen before in ALD patients). When this happens, it is unclear whether the change identified in the ABCD1 gene is harmful (pathogenic) or not harmful (benign), and thus the variants are called “variants of uncertain significance” or VUS. In the case of VUSes, it is particularly important to consider whether the patient has any symptoms or family history and whether their biochemical markers are elevated (See FAQs) to establish an ALD diagnosis. Due to the serious consequences of ALD manifestations, particularly adrenal insufficiency and cerebral ALD in boys, it is important that children with a VUS in the ABCD1 gene still undergo routine monitoring for ALD. Ongoing research studies aim to understand which of these VUSs may truly be pathogenic or benign. ALD Connect is proud to support these studies as a part of our Greyzone Project.

Baby boys identified on the newborn screen as having ALD should be started on a surveillance program with an endocrinologist to monitor adrenal gland function. International ALD experts recommend that screening begin within 6 months after birth and be performed every 3-6 months until age 10, and annually after age 10 throughout adulthood. Boys should also be seen by a neurologist to monitor for the development of cerebral disease. Experts recommend monitoring for cerebral disease with an MRI every 6 months from age 2-12, and shifting to annual MRIs after age 12. More details about recommended monitoring can be found in this international consensus guidelines for ALD paper and this endocrine-specific monitoring guidelines for ALD paper.

Experts typically do not recommend monitoring for adrenal function or cerebral disease in girls identified with ALD on the newborn screen. This is because adrenal insufficiency and cerebral ALD are very rare in girls. Adult women who develop myeloneuropathy should be treated based on symptoms.

A family with a newborn who has confirmed ALD (male or female) should also meet with a genetic counselor to discuss and identify other family members (male and female) who may be at risk for ALD and who should have testing.

ALD Connect hosts a Community Call for Newborn Screening, Young Families, and Parents of Asymptomatic Children each month. This call is usually on the last Wednesday of each month at 7:30 PM Eastern. Be sure to follow us on social media and subscribe to our newsletter to watch for the announcements. You can also bookmark our Community Calendar, which is were we post the links to register for the Community Calls. ALD Connect also hosts a peer mentor program, which connects less experienced community members to more experienced members of a similar phenotypes. You can apply for a peer mentor here.

On May 1, 2021, ALD Connect hosted a Bootcamp for Newborn Screening and Non-Cerebral ALD families. The recordings are below.

ALD Connect is proud to have supported the development of A Parent’s Guide.

This is a wonderful resource for families living with ALD.

Visit adrenoleukodsytrophy.info to learn about the worldwide registry for ABCD1 variants.

Click here to read an update from Dr. Stephan Kemp, Dr. Eric Mallack, and Dr. Mac Engelen on the ABCD1 variant database and the gene’s role in diagnosis.