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Y Maple syrup urine disease (MSUD) results from a deficient enzyme
(branched-chain alpha-keto acid dehydrogenase, BCKD) necessary for
the breakdown of the amino acids leucine, isoleucine, and valine.
Without the BCKD enzyme, these amino acids build up to toxic levels
in the body.
Y MSUD derives its name from the sweet, burnt sugar, or maple syrup
smell of the urine. The disorder affects the way the body metabolizes
(processes) certain components of protein. These components are the
three branched-chain amino acids leucine, isoleucine, and valine.
These amino acids accumulate in the blood causing a toxic effect that
interferes with brain functions. If left untreated, this leads to brain
damage and progressive nervous system degeneration.
Y Maple syrup urine disease is an inherited disorder in which the body is
unable to process certain protein building blocks (amino acids) properly.
Beginning in early infancy, this condition is characterized by poor feeding,
vomiting, lack of energy (lethargy), seizures, and developmental delay.
Y There are several types of maple syrup urine disease. The ë

 ëë 




 ë typically will produce symptoms in newborn infants aged 4-7
days. These symptoms may include:
Y àoor feeding
Y Vomiting
Y àoor weight gain
Y Increasing lethargy (difficult to wake up)
Y Characteristic burned sugar smell to urine
Y Changes in muscle tone, muscle spasms, and seizures
Y Within days they lose their sucking reflex and grow listless, have a
highpitched cry, and become limp with episodes of rigidity. Without
diagnosis and treatment, symptoms progress rapidly to seizures, coma, and
death. In some variant types, failure to thrive may be the first sign. If left
untreated, these infants will die with the first months of life
Y Mutations in the BCKDHA, BCKDHB, DBT, and DLD genes
cause maple syrup urine disease.
Y These four genes provide instructions for making proteins that
work together as a complex. This complex is essential for
breaking down the amino acids leucine, isoleucine, and valine,
which are present in many kinds of food (particularly protein-
rich foods such as milk, meat, and eggs).
Y Mutations in any of these genes reduce or eliminate the function
of the complex, preventing the normal breakdown of leucine,
isoleucine, and valine. As a result, these amino acids and their
byproducts build up in the body. Because high levels of these
substances are toxic to the brain and other organs, their
accumulation leads to the serious medical problems associated
with maple syrup urine disease.
The main mutation occurs
on the 19th chromosome of
a gene that encodes for the
BCKD protein
complex.
When the BCKAD acts
normally it produces
energy and supports
growth. When the
BCKAD is mutated toxins
build up in the
body as well as no energy is
produced.
Also when the gene is
mutated the growth
of the body is hindered.
Y This condition is inherited in an autosomal recessive
pattern, which means both copies of the gene in each
cell have mutations. The parents of an individual with
an autosomal recessive condition each carry one copy
of the mutated gene, but they typically do not show
signs and symptoms of the condition
If there is one defective copy of a
gene in a person no symptoms will
appear and the person will not be
affected. However, if a person has
two defective copies of the gene he
or she will be diagnosed with
MSUD.
Y Treatment requires dietary restriction of branched-chain amino acids, a special
medical formula (drink similar to milk) and intensive dietary monitoring.
Y Treatment of children with MSUD must be started as soon as possible,
preferably at birth. It involves a complex approach of maintaining metabolic
control.
Y A special, carefully controlled diet is the focus of daily treatment. This requires
careful monitoring of protein intake and close medical supervision. The diet
centers on a synthetic formula or "medical food" which provides nutrients and
all the amino acids except leucine, isoleucine and valine. These three amino
acids are added to the diet with carefully controlled amounts of food to provide
the protein necessary for normal growth and development without exceeding
the level of tolerance.
Y Various tests are available to monitor the levels of the amino acids and their
keto acid derivatives in the blood and urine. Illnesses and stress, as well as
consuming too much protein, raise these levels. Even mild illnesses can
become life threatening. A metabolic imbalance requires dietary changes and
at times hospitalization.
Y http://www.msud-support.org/intro.htm
Y http://rarediseases.about.com/od/rarediseases1/a/062
004.htm
Y http://ghr.nlm.nih.gov/condition=maplesyrupurinedis
ease
Y http://www.newbornscreening.info/tools/GraphicsLib
/MSUD.jpg
Y http://adams.bvsd.org/~nancyrichey/GeneticDisorder
s.pdf