The Importance and Implications of Newborn Screening for Lysosomal Storage Disorders


Newborn screening (NBS) has developed throughout the years into a public health prevention program aimed at identifying an increasing number of conditions for which early intervention can prevent premature mortality, morbidity, and disabilities.

From the beginning, NBS has been a regional or state-based effort, which has led to differences in the number of conditions included in each program. To create a more cohesive approach, the Advisory Committee on Heritable Disorders in Newborns and Children (ACHDNC) was established to advise the public health system on which conditions should uniformly be included in all NBS programs. In 2006, the committee accepted recommendations by an expert group of the American College of Medical Genetics and Genomics (ACMG) that every U.S. newborn should be screened for at least 29 core conditions, where evidence suggests that early detection is possible and beneficial.

Since 2007, 12 conditions have been proposed for inclusion on the Recommended Uniform Screening Panel (RUSP). Among those are several lysosomal storage disorders (LSDs)that have been evaluated in limited pilot studies or that are already included in a few national or international newborn screening programs. These conditions include Pompe disease, Niemann–Pick type A/B disease, Fabry disease, Krabbe disease, Mucopolysaccharidoses types I and II, and Gaucher disease.

In a recent article published in the journal Seminars in Perinatology, Mayo Clinic researchers reviewed the current state of newborn screening for these lysosomal storage disorders and discussed their importance in NBS programs.

Dietrich Matern, M.D., Ph.D.

“As for all other conditions included in newborn screening programs, the goal of screening for lysosomal storage disorders is to identify patients with these conditions to initiate treatment before irreversible symptoms develop,” said Dietrich Matern, M.D., Ph.D., first author on this paper and Chair of the Division of Laboratory Genetics and a Consultant in the Department of Laboratory Medicine and Pathology at Mayo Clinic.

As outlined in this review, lysosomal storage disorders have received significant attention in the field of newborn screening over the last 15 years because of the development of treatment options as well as tests that can be performed on large populations. In fact, the U.S. secretary of Health and Human Services added Pompe disease to the RUSP only in March of this year. Other lysosomal storage disorders have been added by only a few programs to their newborn screening panel of conditions, which is in great part due to the persistence of various patient support groups that have provided and continue to provide input and political influence, primarily on the state level.

However, there are questions that remain unanswered, including the cost of screening and test sensitivity and specificity. According to the paper, there is no generally agreed upon specificity threshold that has been applied to NBS methods, and many programs accept low specificity in exchange for improved sensitivity.

“We want a test to have 100-percentsensitivity because that means every affected baby is identified. However, we also want a test that is 100-percent specific, which means only patients with the disease are identified,” said Dr. Matern. “Unfortunately, having it both ways is hardly ever achievable, especially in population screening.”

If a test has 100-percentsensitivity, the specificity of the test will likely be less than 100 percent. This means that some babies will have abnormal results but will not have the disease, resulting in a false positive.

For example, consider a patient with the classic form of Pompe disease. This baby will not survive beyond itsfirst year of life unless treated. However, treatment for Pompe disease is very expensive. Accordingly, every family receiving an abnormal result will have to ponder the fate of their child and the impact of treatment not only in terms of success but also in terms of insurance coverage until further testing clarifies the screening result as false positive.

“We believe it is important to have very few ‘false positive’screening results because it only causes unnecessary anxiety for families who are faced with uncertainty about a potentially lethal or bankrupting condition in their newborn,” said Dr. Matern.

According to the paper, the primary difference between LSDs and other disorders is the high cost of treatment or added risk of treatment. This makes test specificity extremely important to avoid false positives as much as possible while maintaining sensitivity.

As advocacy for screening LSDs continues to grow, they are being added to an increasing number of newborn screening programs in the U.S. and elsewhere. While this is a positive step forward in newborn screening, pediatricians, obstetricians, and midwives need to be aware of their state’s newborn screening panels, the expected or actual false positive rate, and the actions needed to follow up with families whose newborns had an abnormal result.

“Newborn screening for several LSDs will become a reality across the U.S. and other areas within the next three to five years. Improvements to current screening tests, follow-up algorithms, and treatments will be an ongoing activity for all involved in newborn screening,” said Dr. Matern.

For additional information on testing for LSDs, view Mayo Medical Laboratories' comprehensive test menu.

Kelley Luedke

Kelley Luedke

Kelley Luedke is a Marketing Channel Manager at Mayo Clinic Laboratories. She is the principle editor and writer of Insights and leads social media and direct marketing strategy. Kelley has worked at Mayo Clinic since 2013. Outside of work, you can find Kelley running, traveling, playing with her kitty, and exploring new foods.