MAPLE SYRUP URINE DISEASE

ALTERNATE NAMES

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

DESCRIPTION

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. Because of an enzyme defect, individuals with this condition cannot break down the branched chained amino acids leucine, isoleucine, and valine (BCAA). This leads to a buildup of these chemicals in the blood. There are four common forms: 1) Classic MSUD that occurs in infants, usually in the first 2 weeks of life and 2) Intermediate MSUD, 3) Intermittent MSUD and 4) Thiamine-Responsive 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. Early signs and symptoms are poor feeding, vomiting, lethargy, hypo or hypertonia, dystonia, seizures and encephalopathy which can lead to early death or permanent neurologic damage. Later in infancy or childhood, developmental delays are noted. In the intermittent form MSUD can damage the brain during times of physical stress (such as infection, fever, or not eating for a long time) which leads to metabolic decompensation.

DIAGNOSTIC

TESTING, PHYSICAL FINDINGS, AND ICD-9-CM CODING

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.

ICD-9 Code: 270.3

ONSET AND 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 PROGRAMMATIC ASSESSMENT*

Suggested MER for Evaluation: Clinical examination with a description of findings, plasma amino acid test, and urine amino acid test. Lab reports documenting signs of increased leucine, isoleucine, allioleucine and valine. There may also be ketosis and acidosis.

Suggested Listings for Evaluation:

DETERMINATION

LISTING

Meets Listing

111.17, 112.02

Medical Equals