2014

Newborn Screening Method Discovered for Pediatric Disease Made Famous in 1992 Motion Picture, Lorenzo's Oil Identification of X-linked Adrenoleukodystrophy at Birth Allows for Early

Intervention, Improved Outcomes for Males With Rare Genetic Disorder



    BALTIMORE, Sept. 26 /PRNewswire/ -- The current lack of a newborn
 screening method for X-linked Adrenoleukodystrophy (X-ALD) means that many
 boys born with the often deadly genetic disorder are not diagnosed until
 after symptoms develop, putting them past the window of opportunity when
 intervention could spare them from the disease's devastation. But a study
 published in the journal Molecular Genetics and Metabolism presents a
 discovery by researchers at the Kennedy Krieger Institute and Johns Hopkins
 University for utilizing tandem mass spectrometry. By "piggybacking" on
 this existing technology, which has made low-cost screenings for over 50
 genetic disorders possible, ALD can simply be added to the states' existing
 newborn screening programs, allowing for the most widespread, practical
 diagnosis of this genetic disorder.
     "The data from this study supports that a newborn screening can be
 added to existing screening programs, which would allow us to identify
 children with X-ALD and other peroxisomal disorders at birth," said Hugo
 Moser, M.D., Director of the Neurogenetics Research Center at the Kennedy
 Krieger Institute in Baltimore, Md., and senior author of the study.
 "Thanks to the collaborative efforts of researchers at Kennedy Krieger
 Institute and Johns Hopkins University, we have discovered a screening
 method that, if validated in larger trials, will open up a whole world of
 treatment options for boys who would otherwise not be diagnosed until the
 onset of X-ALD's dreadful symptoms."
     When one considers the expanded range of treatment options that are
 available when X-ALD is diagnosed early, which can lead to greatly improved
 outcomes, the rationale for adding a newborn screening is undeniable. For
 one, Addison's Disease, a condition in which the adrenal glands do not
 function properly, occurs in 80 percent of X-ALD patients and is the sole
 cause of death and disability in 50 percent of these patients, yet it is
 completely preventable. Newborn screening will allow physicians to monitor
 adrenal function regularly in X-ALD patients to detect Addison's Disease
 before it causes symptoms, and to then treat it effectively. Furthermore,
 the treatment Lorenzo's Oil was proven in a 2005 study to be effective in
 preventing the onset of X-ALD symptoms, and newborn screening would ensure
 families have the information to seek out this regimen when it can help.
 Lastly, boys diagnosed with X-ALD at birth can be monitored on a regular
 basis by Magnetic Resonance Imaging (MRI) of the brain, thereby allowing
 physicians to identify candidates for bone marrow transplant at the stage
 of the illness when the procedure is most effective.
     "For boys born in the future with the X-ALD gene, this study has
 critical implications because it signals that we have the knowledge base to
 begin to stamp out this disease," said study author Ann B. Moser, Research
 Scientist in Neurology at the Kennedy Krieger Institute. "X-ALD boys
 screened at birth would not only have the chance to benefit from current
 treatments, such as Lorenzo's Oil, they will also be the best candidates
 for any future treatments on the horizon, such as gene therapy and stem
 cell therapy, since treatments are invariably more effective before
 symptoms appear."
     The study analyzed blood samples from 25 male patients with X-ALD, nine
 patients with peroxisome biogenesis disorders and 19 controls using a
 specific tandem mass spectrometry technique known as liquid
 chromatography-tandem mass spectrometry (LC-MS/MS) to identify the chemical
 composition of the samples. Researchers found that the concentration of a
 specific type of lipid known as C26:0 lysophosphatidyl choline (lyso-PC)
 was five to 60 times greater in the samples from males with X-ALD and
 patients with Peroxisome Biogenesis Disorders than in the 19 controls.
 Lyso-PC's contain very long chains of saturated fatty acids, which
 accumulate in abnormally high levels in the brains of individuals with
 X-ALD. This is the first time lyso-PC's have been examined in diagnostic
 studies of X-ALD, and their profile and relative abundance appear to be
 very suitable for screening newborns for X-ALD.
     "This finding truly underscores the tremendous scope of knowledge that
 can be gleaned from the application of innovative newborn screening
 techniques, " said Walter Hubbard, Ph.D., Associate Professor, Division of
 Clinical Pharmacology at Johns Hopkins University School of Medicine. "For
 X-ALD and a myriad other neurological disorders, newborn screenings
 represent the key to improved outcomes."
     Dr. Moser and his co-authors feel that the preliminary results of this
 study are novel and sufficiently promising, but acknowledge that more
 extensive studies must be done before newborns are screened for X-ALD and
 other peroxisomal disorders using LC-MS/MS. The authors have initiated
 studies in collaboration with the States of Maryland and California and the
 Mayo Clinic that will involve hundreds of patients with peroxisomal
 disorders and 60,000 anonymous newborn blood samples. Although these
 studies will take several years to complete, researchers believe this
 method is a probable option for large scale screening that holds the
 potential to drastically change the devastating impact of X-ALD on affected
 boys and their families.
     About X-Adrenoleukodystrophy (X-ALD)
     X-ALD, the most common peroxisomal disorder, causes the breakdown of
 myelin, a fatty substance that acts as an insulator around nerve fibers.
 Approximately 35 - 40 percent of affected males have the classic childhood
 form of the disease, which is more severe and progresses very rapidly.
 Symptoms normally appear between four and 10 years of age, and may include
 visual loss, learning disabilities, seizures, dysphagia, deafness,
 disturbances of gait and coordination, fatigue, intermittent vomiting, and
 progressive dementia, nerve deterioration, loss of verbal communication,
 strength and coordination and, eventually, complete breakdown of bodily
 function. While there is no effective therapy for this form of the disease
 after symptoms develop, diagnosis of X-ALD at birth would allow parents to
 initiate presymptomatic therapy, which studies have shown can prevent it
 from developing.
     About Hugo Moser, M.D.
     Hugo Moser, M.D. is a research scientist and Director of the
 Neurogenetics Research Center at the Kennedy Krieger Institute in
 Baltimore, Maryland. Dr. Moser is also a University Professor of Neurology
 and Pediatrics at Johns Hopkins University. He was previously President of
 the Kennedy Krieger Institute.
     Dr. Moser has focused his research on genetic disorders that affect the
 function of the nervous system in children, particularly those that involve
 a part of the cell referred to as the peroxisome. Of the 15 known
 peroxisomal disorders that lead to mental retardation and nervous system
 disabilities, the most common is X-ALD. Dr. Moser helped to identify the
 characteristic biochemical abnormalities and the gene mutations that cause
 each of these disorders. He established methods of early diagnosis,
 counseling and worldwide programs to evaluate methods of therapy, including
 diet, pharmacological agents and transplantation.
     About the Kennedy Krieger Institute
     Internationally recognized for improving the lives of children and
 adolescents with disorders and injuries of the brain and spinal cord, the
 Kennedy Krieger Institute in Baltimore, MD serves more than 12,000 children
 each year through inpatient and day treatment programs, outpatient clinics,
 home and community services and school-based programs. Kennedy Krieger
 provides a wide range of services for children with developmental concerns
 mild to severe, and is home to a team of investigators who are contributing
 to the understanding of how disorders develop and pioneering new
 interventions and earlier diagnosis. For more information about Kennedy
 Krieger Institute, visit http://www.kennedykrieger.org.
 
 

SOURCE Kennedy Krieger Institute

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