break down three branched-chain amino acids—leucine,
isoleucine, and valine—during the process of digestion.
The deficient enzyme, now known as branched-chain
alpha-keto acid dehydrogenase complex, or BCKD,
was purified and defined in 1978.
Following Dancis’s work, S. E. Snyderman and
his colleagues reported on the first successful dietary
therapy for MSUD in 1964, which they accomplished
by restricting the patients’ intake of foods containing
high levels of branched-chain amino acids. Most pro-
tein-rich foods, such as meat, dairy products, and
eggs, however, contain high levels of BCAAs. Dietary
therapy of MSUD thus consists of a combination of
proteinsubstitutes containing amino acids without
any BCAAs, and enough low-protein or protein-free
foods to meet the patient’s daily caloric requirements.
The MSUD diet of the early 2000s as modified for
different age groups is described in further detail
below.DescriptionMaple syrup urine disease (MSUD)
GENERAL FEATURES.MSUD is an inborn meta-
bolic disorder (IMD), which means that it is a herit-
able disease characterized by the body’s inability to
process one or more specific substances essential to
health. A person diagnosed with MSUD lacks the
enzyme complex that is needed to break down the
three BCAAs. The patient may lack the enzyme com-
plex entirely, it may be inactivated, or it may be only
partially active. In all three cases, the three BCAAs
and their byproducts, which are called ketoacids, build
up in the urine, blood, and other body tissues. In the
classical (most severe) form of the disease, a baby born
with MSUD develops a severe acidosis (abnormally
high levels of acid in the blood) during the first week of
life, followed by seizures and coma caused by swelling
of the brain tissue, and finally death.CAUSES.MSUD is caused by a mutation in any of
four genes, known as BCKDHA, BCKDHB, DBT,
and DLD respectively. These four genes code the pro-
teins that form the BCKD complex, which is needed to
break down BCAAs into smaller molecules. Muta-
tions in any of the four genes will eliminate or reduce
the function of the BCKD complex, thus allowing the
levels of BCAAs and their byproducts in the patient’s
body to rise.
MSUD is an autosomal recessive disease, which
means that a child with MSUD has inherited aSymptoms of Maple Syrup Urine Disease- Urine that smells like maple syrup
- Avoiding food
- Coma
- Feeding difficulties
- High-pitched crying
- Lethargy
- Poor weight gain
- Seizures
- Vomiting
(Illustration by GGS Information Services/Thomson Gale.)KEY TERMS
Amino acid—One of 20 organic acids used as the
building blocks of proteins in humans and other
animals. The three amino acids involved in
MSUD are called branched-chain amino acids or
BCAAs because their chemical structures have side
chains of carbon atoms that form a branch rather
than a straight line.
Autosomal recessive—A term used to describe a
pattern of genetic inheritance in which a child
receives two copies of a defective gene, one from
each parent, on an autosome (a nonsex chromo-
some). MSUD is an autosomal recessive disorder.
Branched-chain alpha-keto acid dehydrogenase
(BCKD)—The chemical name of the enzyme that
is missing or partially inactivated in patients with
MSUD.
Carrier—A person who harbors an infectious agent
or a defective gene without showing clinical signs
of disease themselves and who can transmit the
infection to others or the defective gene to their
children.
Cerumen—The waxy substance secreted by glands
in the external ear canal. It can be tested to screen
newborns for MSUD.
Dialysis—A method of artificial kidney function
used to remove waste products or other substances
from the patient’s body fluids. In the case of patients
with MSUD, dialysis may be used to remove
BCAAs from the patient’s body during an acute
episode requiring hospitalization.
Leucine—An essential amino acid and one of the
three branched-chain amino acids implicated in
MSUD. Leucine is the most toxic of the three and
the one whose level is most closely monitored in
dietary therapy for MSUD.Maple syrup urine disease