ALTERNATE NAMES

BCKD; DeficiencyBranched-Chain Alpha-Ketoacid Dehydrogenase Deficiency; Branched-Chain Ketoaciduria; MSUD

Maple syrup urine disease (MSUD) is an inherited metabolic disorder in which the body is unable to process certain protein building blocks (amino acids) properly. Because these amino acids are not metabolized, they, along with their various byproducts, abnormally accumulate in the cells and fluids of the body. The condition gets its name from the distinctive sweet odor of the affected infant’s earwax, sweat, and urine.

Mutations in the BCKDHA, BCKDHB, DBT, and DLD genes cause MSUD. Individuals with this condition cannot break down the branched chained amino acids (BCAA) leucine, isoleucine, and valine . This leads to a buildup of these chemicals in the blood.

There are four common forms:

1. 1. 

   Classic MSUD In the classic form, the disorder presents after the infant has had milk containing protein. This causes an increase in the offending amino acids which become toxic to the brain. Classic MSUD tends to impair intellectual development and bone growth.

2. 2. 

   Intermediate MSUD Onset of symptoms of intermediate MSUD is later than in the classic form, typically between six months and seven years of age.

3. 3. 

   Intermittent MSUD In the intermittent form, growth and intellectual development are normal. Stressors such as infections, fever, or hunger can cause brain damage, leading to episodes of metabolic decompensation. Such episodes are potentially catastrophic and fatal.

4. 4. 

   Thiamine-Responsive MSUD This form has shown favorable response to treatment with thiamine (vitamin B1) along with diet restrictions.

DIAGNOSTIC TESTING, PHYSICAL FINDINGS, AND ICD-9-CM/ICD-10-CM CODING

Diagnostic testing: Diagnostic testing for MSUD includes blood and urine amino acid tests that measure the levels of leucine, isoleucine, alloioleucine, and valine. If MSUD is found, there will be signs of ketosis and excess acid (acidosis). These are measured in the usual newborn screening test.

Physical findings: Symptoms include:

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  Poor feeding;

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  Vomiting;

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  Lethargy;

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  Hypotonia (low muscle tone) or hypertonia (increased muscle tone);

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  Dystonia (uncontrolled muscle contractions); and

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  Seizures.

ICD-9: 270.3

ICD-10: E70.1

PROGRESSION

If the disease is not treated, MSUD can lead to seizures, coma, and death at any age. In the intermittent type symptoms become apparent later in infancy or childhood and are typically milder. Long-term sequelae may include developmental delays, learning problems, seizures, and motor difficulties. Even with dietary treatment, stressful situations, and illness can still cause high levels of certain amino acids. Death may occur during these episodes.

TREATMENT

When the condition is diagnosed and during episodes, treatment involves eating a protein-free diet and correction of the metabolic consequences of the elevated amino acid levels. A special intravenous solution decreases the leucine level (the most toxic) and corrects the energy deficits.

In the intermittent form a special diet containing low levels of the offending amino acids is required. Even with treatment affected individuals remain at risk for developing episodes of acute illness (metabolic crisis), often triggered by infection, injury, failure to eat (fasting), or psychological stress. During these episodes there is a rapid, sudden spike in amino acid levels necessitating immediate medical intervention. For acute toxic episodes the management is the same as in the classic form.

In the Thiamine-responsive form, administration of thiamine and consumption of a low protein diet results in a reduction of amino acid levels to normal. Withdrawal of thiamine treatment results in a rapid rebound in the elevation of plasma amino acid concentration.

Suggested MER for Evaluation:

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  Clinical examination with a description of findings;

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  Plasma amino acid test, and urine amino acid test; and

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  Lab reports documenting signs of increased leucine, isoleucine, allioleucine, and valine. There may also be ketosis and acidosis.

Suggested Listings for Evaluation:

DETERMINATION

LISTING

REMARKS

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