Navigation Links
Newborn screening for DMD shows promise as an international model
Date:3/19/2012

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
Erin.Pope@NationwideChildrens.org
614-355-0495
Nationwide Children's Hospital
Source:Eurekalert

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:
*Name:
*Comment:
*Email:
(Date:4/25/2017)... ... April 25, 2017 , ... ProRehab Physical ... be the preferred physical therapy provider for Derby City CrossFit, effective immediately. , ... CrossFit as quickly and effectively as possible, ProRehab’s sports physical therapists will work ...
(Date:4/25/2017)... ... April 25, 2017 , ... ... to compare student test score performance for the 2015-16 school year across Wisconsin’s ... voucher programs. Though it highlights important patterns in student test score performance, the ...
(Date:4/25/2017)... Switzerland (PRWEB) , ... April 25, 2017 , ... ... innovation targets, they rely on contracted partners to help with process innovation in ... of combined drug formulation experience along with state-of-the-art analytical equipment in support of ...
(Date:4/25/2017)... (PRWEB) , ... April 25, 2017 , ... Saad B. Chaudhary, MD is committed to ... of acute or chronic problems, I focus on preventative care with all my patients to ... have any questions, always feel free to contact my office and my trained staff will ...
(Date:4/25/2017)... ... , ... Vetoquinol USA® , a world-class developer of ... the EQUISTRO line, at this week’s Rolex Kentucky Three-Day Event in Lexington. Flexadin ... , The scientifically-developed Flexadin UCII supports the body’s normal repair of cartilage and ...
Breaking Medicine News(10 mins):
(Date:4/19/2017)... DALLAS , April 19, 2017 /PRNewswire/ ... that the first patients in Nashville ... in the Lower Esophageal Sphincter Stimulation for GERD (LESS ... device designed to provide long-term reflux control by restoring ... GERD affects nearly 65 million people in ...
(Date:4/19/2017)...  New research provides evidence that an old drug may ... study released today that will be presented at the ... Boston , April 22 to 28, 2017. ... disease, the oral drug levodopa has long been considered the ... the disease progresses, the effects of the medication can partially ...
(Date:4/18/2017)... Cogentix Medical, Inc. (NASDAQ: CGNT), a global medical device ... markets with innovative and proprietary products, will release financial ... after the market close on Tuesday, May 2, 2017. ... call and webcast to discuss its financial results the ... p.m. Eastern Time (3:30 p.m. Central Time). Darin ...
Breaking Medicine Technology: