Amino Acid Disorders

Print Version
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
E3=7q31-32
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.
OMIM Link http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=248600
Genetests Link www.genetests.org
Support Group

The MSUD Family Support Group
http://www.msud-support.org

National Coalition for PKU and Allied Disorders
http://www.pku-allieddisorders.org/

Children Living with Inherited Metabolic Diseases
http://www.climb.org.uk/

  Print Version
   

DISCLAIMER:

THIS INFORMATION DOES NOT PROVIDE MEDICAL ADVICE. All content ("Content"), including text, graphics, images and information are for general informational purposes only. You are encouraged to confer with your doctor or other health care professional with regard to information contained on this information sheet. After reading this information sheet, you are encouraged to review the information carefully with your doctor or other healthcare provider. The Content is not intended to be a substitute for professional medical advice, diagnosis or treatment. NEVER DISREGARD PROFESSIONAL MEDICAL ADVICE, OR DELAY IN SEEKING IT, BECAUSE OF SOMETHING YOU HAVE READ ON THIS INFORMATION SHEET. This project is supported by a grant from the Maternal and Child Health Bureau, Health Resources and Service Administration, Genetic Services Branch, MCH Project #:1H46 MC 00189-03 http://mchb.hrsa.gov