Duchenne Newborn Screening Will Identify Other Conditions

December 21, 2015

Routine screening of newborns for Duchenne muscular dystrophy (DMD) is under consideration in the United States and elsewhere in the world because of recent developments in diagnostics and treatments.

Some of the implications of such screening are discussed in a review paper published recently in JAMA Neurology.

Senior author, Robert C. Griggs, MD, University of Rochester School of Medicine and Dentistry, New York, explained to Medscape Medical News that it is now realized that identifying patients with DMD at a very early age will be advantageous because corticosteroid therapy can be started before muscle fibrosis has developed and symptoms have clinically manifested.

"Other new treatments, including genetic therapies, are also becoming available, and we believe early treatment will be beneficial," he added.

He said the field is following in the footsteps of cystic fibrosis. Early identification of patients with this disease has led to improved care, which, in turn, has tripled the lifespan of those affected. "We hope similar strides can be made with Duchenne."

The test for DMD involves screening for elevated creatine kinase (CK) levels. These individuals would then undergo a genetic analysis, which Dr Griggs believes could lead to 95% of DMD cases being identified.

Although DMD affects mainly boys because it is an X-linked recessive condition, Dr Griggs recommends that both male and female babies be screened. He points out that it is actually logistically easier to screen all newborns rather than limit testing to boys only.

In addition, some girls can develop DMD — for example, those with Turner's syndrome, who only have one X chromosome, and others with endocrine issues and who are actually genetically male — and by screening girls, carriers of DMD will also be identified.

The review paper draws on experience from pilot screening programs already completed or underway. The authors note that other conditions characterized by raised CK levels will be discovered with such screening, adding that a protocol for further evaluation and management of patients with elevated CK levels and negative results on DMD gene testing should be developed.

"This highlights the importance of identification of alternative diagnoses with elevated neonatal CK levels and providing guidance to physicians who follow up these patients," the authors write.

Such conditions include congenital muscular dystrophy and the more commonly Identified limb girdle muscular dystrophies, α-sarcoglycanopathy and dysferlinopathy.

"Many of these other conditions may well be the subject of new treatments in development, too. The whole field is moving forward now," Dr Griggs said.

The authors note that although the sensitivity of initial CK screening for DMD is high, there will also be a possibility of some false-negative results.

They note that false-negative results are an issue because an elevated CK level is a marker that is secondary to the disease process and not a specific indicator of DMD.

Screening newborn CK levels is likely to miss some female DMD carriers, cases of Becker muscular dystrophy, and patients with X-linked cardiomyopathy, they state.

Dr Griggs reported serving as a consultant for Marathon Pharmaceutical, PTC Therapeutics, Sarepta Pharmaceuticals, and Taro Pharmaceuticals and receiving research grant support from the Muscular Dystrophy Association, the National Institutes of Health, and the Parent Project for Muscular Dystrophy for a clinical trial of corticosteroids in DMD. Other authors have reported being a consultant for Biomarinm, serving on the scientific advisory board of Alexion Pharma, and receiving honoraria for select invited industry-sponsored webinars and symposia.

JAMA Neurol. Published online November 23, 2015. Abstract

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