Amino Acid Disorders

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Disease Name Maple syrup urine disease
Alternate name(s) Branched chain ketoaciduria, Branched chain alpha-keto dehydrogenase deficiency
Acronym MSUD type 1A, BCKD deficiency
Disease Classification Amino Acid Disorder
Variants Yes
Variant name MSUD type 1B, MSUD Type II, Intermittent branched-chain ketoaciduria, Intermediate branched-chain ketoaciduria, Thiamine responsive MSUD
Symptom onset Neonatal with some variability
Symptoms Lethargy progressive to coma and possible death, vomiting, difficulty feeding, opisthotonic posturing, hypoglycemia, possible high pitched cry.
Natural history without treatment Neurologic abnormalities and profound mental retardation.
Natural history with treatment Normal IQ and development may be expected if treatment is initiated before first crisis, but development is delayed in the severest cases.
Treatment Dietary restriction of the branched chain amino acids and supplementation with medical formula. Thiamine supplementation in thiamine responsive patients.
Other “Maple syrup”-like odor to urine (usually present during crisis)
Physical phenotype None
Inheritance Autosomal recessive
General population incidence 1:200,000
Ethnic differences Yes
Population Mennonites, French-Canadians
Ethnic incidence 1/760 (Mennonites)
Enzyme location Inner mitochondrial membrane; liver, kidney, leukocytes and fibroblasts.
Enzyme Function Catalyzes the decarboxylation of oxoacids.
Missing Enzyme Branched-chain ketoacid dehydrogenase (BCKAD). This enzyme is a multienzyme complex with 3 components – E1, E2 and E3.
Metabolite changes Increased leucine, isoleucine and valine in plasma and urine, increased organic acids in urine.
Gene Four genes are involved in formation of multicomplex enzyme.
Gene location E1alpha = 19q13.1-13.2
E1beta = 6p21-22
E2 = 1p31
DNA testing available Yes
DNA testing detail Common mutation present in Mennonites (Y393N-alpha) and comprehensive DNA mutation analysis.
Prenatal testing Enzyme testing by CVS or amnio. If mutation is known, DNA testing may be available.
MS/MS Profile Leucine elevated, leucine to alanine ratio elevated.
Genetests Link
Support Group

The MSUD Family Support Group

National Coalition for PKU and Allied Disorders

Children Living with Inherited Metabolic Diseases

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