DMD Research: Diagnostic Delays Common

New survey shows average of 2.5 years elapse between symptom onset and diagnosis of DMD

by Quest Staff on September 7, 2009 - 9:00pm

A study that analyzed medical records from four U.S. states has found that the average time between symptom onset and diagnosis of Duchenne muscular dystrophy (DMD) is 2.5 years, an interval that hasn't changed in two decades.

This delay in identification postpones treatment that can slow the progression of the disease and results in lost opportunities for genetic counseling of parents.

Emma Ciafaloni, a neurologist and neuromuscular disease specialist at the University of Rochester (N.Y.) Medical Center, and colleagues, published the findings in the September 2009 issue of the Journal of Pediatrics.

Ciafaloni is associated with the MDA clinic at her institution, and several other study authors are MDA clinic directors.

Dr. Miller and patient
New findings show the time between the first signs of DMD and a definitive diagnosis hasn't changed in two decades. Faster diagnosis would allow prompt genetic counseling for families and earlier treatment for patients.

The researchers say pediatricians and other providers of primary care could speed up the diagnostic process considerably by checking blood levels of creatine kinase (CK) early in the evaluation of boys with developmental delays. CK is an enzyme that leaks out of damaged muscle tissue, and the serum CK level is elevated 50 to 200 times above normal in children with DMD, most of whom are boys.

About DMD

DMD is a genetic disease that involves progressive degeneration of voluntary and cardiac muscles, with resulting weakness and heart abnormalities, beginning in early childhood.

Delayed motor milestones are an early sign of DMD, and cognitive, behavioral or language abnormalities are seen in about a third of cases. Loss of the ability to walk occurs in most children with DMD between ages 10 and 12; weakened cardiac and respiratory muscles severely limit life span.

Corticosteroid medications, such as prednisone, slow disease progression.

The disease results from any of a number of mutations in the gene for dystrophin, a muscle and brain protein. Almost no dystrophin is produced in the muscles of children with DMD. The dystrophin gene is located on the X chromosome, and, like other X-linked genetic diseases, DMD affects males almost exclusively, although some girls are affected.

A serum CK level is considered a good screening test for DMD, although DNA testing is required to confirm the diagnosis.

Becker muscular dystrophy (BMD) is a less severe and less predictable form of MD. It occurs as a result of mutations in the dystrophin gene that allow some limited production of functional dystrophin.

About the new findings

The investigators collected data from the medical records of 156 patients whose eventual diagnosis was DMD. All patients were living in Arizona, Colorado, Iowa or Western New York state, and none had any known family history of the disease.

The investigators say signs or symptoms of DMD in the children were first noted by parents or caregivers at an average age of 2.5 years. The average time elapsed between noticing the first symptom and bringing the child to a health-care provider was one year, prompting evaluation of the child at an average age of 3.6 years.

The average age for a first evaluation by a neurologist or neuromuscular disease specialist was 4.6 years, and the first CK level was checked at an average age of 4.7 years. A pediatrician or family practitioner ordered the first CK level only 37 percent of the time.

Petra Kaufmann, who directs the MDA clinic at Columbia University Medical Center in New York, authored an editorial published with the findings.

"The initial screen, a blood test for creatine kinase, is widely available and inexpensive," she writes. "In the past, one might have argued that little is gained by making an earlier diagnosis of an 'incurable' disease. Today, effective treatments are available that can temporarily preserve motor function and prolong survival. There is therefore newfound urgency in making a correct diagnosis that will become more pressing as novel treatments enter clinical trials."

These “novel treatments” include Ataluren (originally called PTC124), a drug developed by PTC Therapeutics with assistance from MDA, which is now in clinical testing. This drug coaxes cells to reinterpret genetic information so that functional dystrophin protein can be produced.

Adding functional dystrophin genes (gene therapy) is another strategy being investigated by MDA researchers.

About MDA's role

The diagnostic interval study was conducted under the auspices of the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet), with support from the U.S. Centers for Disease Control and Prevention (CDC).

MDA was instrumental in the passage of the 2001 MD CARE Act, which laid the foundation for MD STARnet. Valerie Cwik, Medical Director at MDA, and Annie Kennedy, MDA's Vice President for Advocacy, are part of the CDC-funded National Task Force for Early Identification of Neuromuscular Diseases.

MDA considers earlier diagnosis of DMD to be of paramount importance, because it provides parents with accurate information with which to make reproductive decisions, and because evidence suggests that the benefits of treatments now in development will be maximized if they're started as early in childhood as possible.

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