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
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
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