By NURDAN PEKACAR KELEŞOĞLU

What is maple syrup urine disease?

What genes are related to maple syrup

urine disease?

How do people inherit maple syrup urine

disease?

Treatment of maple syrup urine disease

 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.
 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.
 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.
 There are several types of maple syrup urine disease. The most
common (classic) form typically will produce symptoms in
newborn infants aged 4-7 days. These symptoms may include:
 Poor feeding
 Vomiting
 Poor weight gain
 Increasing lethargy (difficult to wake up)
 Characteristic burned sugar smell to urine
 Changes in muscle tone, muscle spasms, and seizures
 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
 Mutations in the BCKDHA, BCKDHB, DBT, and DLD
genes cause maple syrup urine disease.
 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).
 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.
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.
 Treatment requires dietary restriction of branched-chain amino
acids, a special medical formula (drink similar to milk) and
intensive dietary monitoring.
 Treatment of children with MSUD must be started as soon as
possible, preferably at birth. It involves a complex approach of
maintaining metabolic control.
 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.
 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.
http://www.msud-support.org/intro.htm
http://rarediseases.about.com/od/rarediseases1/a/
http://ghr.nlm.nih.gov/condition=maplesyrupurine
http://www.newbornscreening.info/tools/GraphicsL
http://adams.bvsd.org/~nancyrichey/GeneticDisor