Navigation Links
Newborn screening for DMD shows promise as an international model

Investigators at Nationwide Children's Hospital, working with the DNA Sequencing Core Facility at the University of Utah, have developed an approach to newborn screening (NBS) for the life-threatening genetic disorder, Duchenne muscular dystrophy (DMD) and potentially other muscular dystrophies. As a model for NBS, the approach published online in January in the Annals of Neurology provides evidence that this approach could be implemented if approved by regulatory bodies at a state level or alternatively through the Secretary's Advisory Committee on Heritable Disorders in Newborns and Children.

DMD is the most common, severe childhood form of muscular dystrophy, inherited as an X-linked recessive disorder. Progressive muscle weakness with loss of ambulation by 12-to-13 years of age is the expected outcome. Heart involvement is significant and may require treatment to avert premature death. On average, patients are diagnosed with DMD at 5 years of age, although parents often notice impaired motor skills at an earlier age.

Over the last three decades, creatine kinase (CK) testing on dried blood spots has been attempted as a method for newborn screening for DMD. CK is an enzyme that leaks into the blood from damaged muscle cells; it is markedly elevated in DMD and some other muscular dystrophies. Using CK testing on dried blood spots derived from heel-sticks to identify DMD cases during the newborn period was validated in 1979 and launched a pathway for this method of testing at birth. If CK was elevated, it was repeated at four to six weeks of age on venous blood obtained in the doctor's office. If elevation persisted, blood was again taken and DNA was isolated from white blood cells and tested for DMD mutations to establish a definitive diagnosis. This three-step screening process took shape in New Zealand and spread to programs in Edinburgh, Germany, Canada, France, Wales, Cyprus and Belgium and Western Pennsylvania. The longest running DMD newborn screening program in history, in Wales, recently closed. To this day, Antwerp, Belgium is home to the only program that maintains newborn screening for DMD.

"The three-step model is poorly adapted to newborn screening in the USA," said Jerry R. Mendell, MD, principal investigator of the study and current director of the Center for Gene Therapy at The Research Institute at Nationwide Children's Hospital. "It can work efficiently in a publically-funded health care system where newborn care is designated at specific times post-delivery making follow-up blood draws a realistic part of the total program for child welfare." In the USA, mother and child are discharged within 24 to 48 hours following uncomplicated deliveries and post-natal care cannot be enforced. Thus, many newborns with elevated CKs at birth would be lost to follow up.

The two-tier system developed by Dr. Mendell permits heel blood taken at birth to be tested initially for CK with follow up DNA testing for DMD. A CK is obtained on the dried blood spot and if the level exceeds a predetermined threshold, DNA testing is automatically done from the same sample. No follow up blood samples are required. "This two-tier system (CK and DNA testing on same sample) is practical, comprehensive, and cost effective," said Dr. Mendell, who is also a faculty member in The Ohio State University College of Medicine.

Promising new DMD therapies have rekindled interest in establishing a pathway for newborn screening in the DMD patient population. In 2004, Center for Disease Control workshop participants concluded that early diagnosis of DMD could have potential advantages for families, considering multiple treatment strategies were on the horizon. Funds were made available to Dr. Mendell and his team at Nationwide Children's Hospital to explore the feasibility for establishing a model for DMD newborn screening in the United States.

The study appearing in Annals of Neurology documents a nearly-four-year pilot study of a voluntary DMD newborn screening program in Ohio. Over the course of the study, 37,749 newborn boys were screened and six were discovered to have DMD gene mutations. In cases where CK was elevated and DMD mutations were not found, the investigators extended the study to identify limb-girdle muscular dystrophy (LGMD) gene mutations as part of the screening process. The published study results confirmed that this was possible and reported that three of the cases had gene mutations found in LGMD.

"The program we have introduced differs from past programs and the current Antwerp approach to newborn screening for DMD that require a three-step process," said Dr. Mendell. "This new process fits current U.S. obstetrics practices and allows us to readily distinguish false and true positive test results."

Whether DMD treatment has advanced to the point of justifying newborn screening is a judgment yet to be made by state and federal agencies. "If and when an early therapy that improves the health outcome for individuals with DMD becomes available, our study serves as a model for implementation of newborn screening for DMD," said Dr. Mendell.


Contact: Erin Pope
Nationwide Children's Hospital

Related medicine news :

1. Newborn screening program aims to help transform treatments for genetic diseases detected at birth
2. Antibiotics in Pregnancy May Shield Newborns From Strep B
3. Northwestern researchers trial new device that may support improved newborn health
4. Toll-like receptors play role in brain damage in newborns
5. 2 breakthrough innovations to address maternal and newborn deaths in Sub-Saharan Africa
6. New mothers, newborns happy with home visits
7. Flu Shots for Pregnant Women Also Protect Newborns
8. Protein May Help Spot Newborns With Brain Damage
9. Parents anxiety about newborn screening results does not lead to increased health care use
10. Steps Outlined to Screen All Newborns for Heart Defects
11. Newest screen for newborns will indicate heart problems
Post Your Comments:
(Date:11/28/2015)... ... 28, 2015 , ... Safe storage for contraceptive devices may not always be ... New Jersey and the other from Bradley Beach, New Jersey, there is an easy ... of having to replace NuvaRings more often than necessary. As such, it affords peace ...
(Date:11/27/2015)... CA (PRWEB) , ... November 27, 2015 , ... According ... at the recent 2015 American Dental Association meeting in Washington D.C. revolved around the ... protect a patient’s overall health. The talk stressed the link between periodontal disease (more ...
(Date:11/27/2015)... ... November 27, 2015 , ... ... and convenient way to dispense prescription medications at home, so he invented the ... to monitor and dispense prescription medications. In doing so, it could help to ...
(Date:11/27/2015)... ... , ... MPWH, the No.1 Herpes-only dating community in the world, revealed that over 50% of ... than 3.7 billion people under the age of 50 – or 67% of the population ... global estimates of HSV-1 infection . , "The data shocks us highly!" said Michelle ...
(Date:11/27/2015)... ... 2015 , ... Keeping in mind challenges faced by parents ... consultation, has collaborated with a leading web-based marketplace for extra-curricular activities for children ... and bring advice from parenting experts within their reach. As a part of ...
Breaking Medicine News(10 mins):
(Date:11/26/2015)... , November 26, 2015 /PRNewswire/ ... --> adds "Global ... and "Investigation Report on China Repaglinide ... 2021 forecasts data and information to ... . --> ...
(Date:11/26/2015)... Nov. 26, 2015 Research and Markets ... the "2016 Future Horizons and Growth Strategies ... Supplier Shares, Country Segment Forecasts, Competitive Intelligence, Emerging ... --> --> This ... the Italian therapeutic drug monitoring market, including emerging ...
(Date:11/26/2015)... , November 26, 2015 ... the addition of the  "2016 Future ... European Cell Surface Marker Testing Market: ...  report to their offering.  --> ... addition of the  "2016 Future Horizons ...
Breaking Medicine Technology: