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 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 National Coalition for PKU and Allied Disorders |
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