||Maple Syrup Urine Disease
|Condition: Maple Syrup Urine Disease
"Maple Syrup Urine Disease is caused by a baby's inability to use several aminio acids. The baby's urine smells like maple syrup. This disorder leads to mental retardation, seizures and usually death. A special low protein diet helps to avoid many of these problems." - Vermont Newborn Screening
More technical information from the Mountain States Genetic Network:
Maple Syrup Urine Disease (MSUD) is a rare autosomal recessive inherited disorder of catabolism of the branched chain amino acids (BCAA) leucine, isoleucine, and valine and their respective branched chain ketoacids (BCKA).
Metabolic Pathway: MSUD
There are multiple clinical phenotypes characterized by a spectrum of signs and symptoms ranging from life-threatening to mild. The most common form of the condition, classic MSUD, is life-threatening in early infancy and requires prompt medical intervention. Classic MSUD is due to absent activity of the mitochondrial enzyme complex-branched chain alpha-ketoacid dehydrogenase. It occurs with an incidence of approximately 1:200,000 infants.
Symptoms of MSUD begin shortly after birth concomitant with the ingestion of dietary protein. Because the ingestion of the branched chain amino acids exceeds metabolic requirements for growth, and catabolism of the excess amino acids is blocked, the BCAA and BCKA accumulate in blood and are excreted in the urine. Signs and symptoms progress from poor feeding, irritability, and vomiting to lethargy and coma in the first weeks of life. Hypoglycemia and a strongly positive test for urine ketones may be present. The BCKA may impart a maple syrup or burnt sugar odor to the urine (which gives the disease its name). Without rapid treatment, death or permanent neurologic damage may result.
As with most other inherited disorders, there are variant forms of MSUD due to genetic mutations that reduce but do not eliminate enzyme activity. These include the intermediate, intermittent, and thiamine-responsive forms. The incidence of these variant forms in the general population is not known, and whether these variant forms of MSUD will be detected by newborn screening has not been determined.
Elevation of leucine is detected by a bacterial inhibition assay. Normal leucine levels are < 4 mg/dL. Even transient elevation of plasma leucine in the normal newborn is unusual unless the infant is premature and/or receiving IV amino acid preparations.
Any screening value greater than or equal to 4 mg/dL should be evaluated immediately. Any newborn in whom the plasma leucine level is 4 mg/dl or greater should be considered to have MSUD until proven otherwise. Contact with a metabolic center should be initiated for assistance in diagnosis and management. If the infant has symptoms of MSUD, the infant should be transferred to the metabolic center for specialized emergency intervention. (Refer to the directory for a metabolic consultant in your state.)
Long-term treatment consists of the administration of nutrition low in the branched chain amino acids. A protein-restricted diet will need to be maintained for life. Studies have shown that early diagnosis and appropriate long-term management may improve neurologic development.
Screening Practice Considerations
Plasma BCAA levels begin to rise immediately after birth, however significant increases in the levels require protein ingestion or catabolism. Early discharge of infants may result in inadequate increases in BCAA levels for detection by newborn screening.
Prompt confirmatory testing is required even if there is evidence to suggest that one of the situations associated with false positive screens is present (these include early specimen collection, prematurity, heat-damaged specimen, hyperalimentation, or antibiotic therapy). The presence of any of these does not exclude the possibility of disease.
The purpose of newborn screening is to identify infants at risk and in need of more definitive testing.
As with any laboratory test, both false negative and false positive results are possible.
Screening test results are insufficient information on which to base diagnoses or treatment.