MSUD
MCID: MPL001
MIFTS: 69

Maple Syrup Urine Disease (MSUD)

Categories: Genetic diseases, Mental diseases, Metabolic diseases, Nephrological diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Maple Syrup Urine Disease

MalaCards integrated aliases for Maple Syrup Urine Disease:

Name: Maple Syrup Urine Disease 56 12 74 24 52 25 58 73 36 29 54 6 43 15 39 71
Bckd Deficiency 56 24 52 25 58 73
Msud 56 24 52 25 58 73
Branched-Chain Ketoaciduria 56 52 25 58 73
Branched-Chain Alpha-Keto Acid Dehydrogenase Deficiency 56 52 25 73
Intermittent Maple Syrup Urine Disease 58 73 71
Keto Acid Decarboxylase Deficiency 56 52 73
Maple Syrup Urine Disease, Type Ii 56 13 71
Classic Maple Syrup Urine Disease 58 73 71
Branched-Chain 2-Ketoacid Dehydrogenase Deficiency 52 58
Thiamine-Responsive Maple Syrup Urine Disease 58 73
Intermediate Maple Syrup Urine Disease 73 71
Maple Syrup Urine Disease, Type Ia 56 71
Maple Syrup Urine Disease Type 1a 29 6
Maple Syrup Urine Disease Type 1b 29 6
Maple Syrup Urine Disease Type 2 29 6
Branched Chain Ketoaciduria 12 52
Bckdh Deficiency 52 58
Thiamine-Responsive Branched-Chain Alpha-Ketoacid Dehydrogenase Deficiency 58
Intermittent Branched-Chain Alpha-Ketoacid Dehydrogenase Deficiency 58
Classic Branched-Chain Alpha-Ketoacid Dehydrogenase Deficiency 58
Lactic Acidosis, Congenital Infantile, Due to Lad Deficiency 71
Branched-Chain Ketoacid Dehydrogenase Deficiency 24
Dihydrolipoamide Dehydrogenase Deficiency 12
Nadh Cytochrome B5 Reductase Deficiency 71
Classic Branched-Chain Ketoaciduria 58
Thiamine-Responsive Bckd Deficiency 58
Classical Maple Syrup Urine Disease 29
Maple Syrup Urine Disease, Type Ib 56
Maple Syrup Urine Disease, Type 1b 71
Maple Syrup Urine Disease Type Ia 73
Maple Syrup Urine Disease Type Ib 73
Maple Syrup Urine Disease Type Ii 73
Intermittent Bckd Deficiency 58
Maple Syrup Urine Disease 1a 73
Maple Syrup Urine Disease 1b 73
Maple Syrup Urine Disease 2 73
Thiamine-Responsive Msud 58
Classic Bckd Deficiency 58
Maple Syrup Disease 24
Intermittent Msud 58
Ketoacidaemia 12
Ketoacidemia 25
Classic Msud 58
Msud Type Ia 73
Msud Type Ib 73
Msud Type Ii 73
Ketonemia 71
Msud1a 73
Msud1b 73
Msud2 73

Characteristics:

Orphanet epidemiological data:

58
maple syrup urine disease
Inheritance: Autosomal recessive; Prevalence: 1-9/1000000 (Worldwide),1-9/1000000 (United States),1-9/1000000 (Italy),1-9/100000 (Tunisia),1-9/1000000 (Japan),1-9/100000 (Portugal),1-9/1000000 (Australia),1-9/1000000 (Taiwan, Province of China); Age of onset: Childhood,Infancy,Neonatal; Age of death: early childhood,infantile,late childhood;
classic maple syrup urine disease
Inheritance: Autosomal recessive; Age of onset: Neonatal; Age of death: any age;
thiamine-responsive maple syrup urine disease
Inheritance: Autosomal recessive; Age of onset: Infancy;
intermittent maple syrup urine disease
Inheritance: Autosomal recessive; Age of onset: Childhood,Infancy,Neonatal; Age of death: normal life expectancy;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
five clinical variants of msud unassociated with genotype
(1) classic severe (onset of symptoms 4 to 7 days of age)
(2) intermittent
(3) intermediate
(4) thiamine-responsive form
(5) dihydrolipoyl dehydrogenase (e3)-deficient
worldwide incidence of 1 in 185,000 live births
in inbred old order mennonite population of lancaster county, msud prevalence is 1/176 newborns
death in untreated children


HPO:

31
maple syrup urine disease:
Inheritance autosomal recessive inheritance
Onset and clinical course recurrent


Classifications:

Orphanet: 58  
Inborn errors of metabolism


External Ids:

Disease Ontology 12 DOID:9269
OMIM 56 248600
OMIM Phenotypic Series 56 PS248600
KEGG 36 H00172
MeSH 43 D008375
NCIt 49 C34806
SNOMED-CT 67 27718001
ICD10 32 E71.0
MESH via Orphanet 44 D008375
ICD10 via Orphanet 33 E71.0
UMLS via Orphanet 72 C0024776 C0268568 C0268569 more
UMLS 71 C0024776 C0235430 C0268193 more

Summaries for Maple Syrup Urine Disease

UniProtKB/Swiss-Prot : 73 Maple syrup urine disease: A metabolic disorder due to an enzyme defect in the catabolic pathway of the branched-chain amino acids leucine, isoleucine, and valine. Accumulation of these 3 amino acids and their corresponding keto acids leads to encephalopathy and progressive neurodegeneration. Clinical features include mental and physical retardation, feeding problems, and a maple syrup odor to the urine. The keto acids of the branched- chain amino acids are present in the urine. If untreated, maple syrup urine disease can lead to seizures, coma, and death. The disease is often classified by its pattern of signs and symptoms. The most common and severe form of the disease is the classic type, which becomes apparent soon after birth. Variant forms of the disorder become apparent later in infancy or childhood and are typically milder, but they still involve developmental delay and other medical problems if not treated.
Maple syrup urine disease 1A: A metabolic disorder due to an enzyme defect in the catabolic pathway of the branched-chain amino acids leucine, isoleucine, and valine. Accumulation of these 3 amino acids and their corresponding keto acids leads to encephalopathy and progressive neurodegeneration. Clinical features include mental and physical retardation, feeding problems, and a maple syrup odor to the urine. The keto acids of the branched- chain amino acids are present in the urine. If untreated, maple syrup urine disease can lead to seizures, coma, and death. The disease is often classified by its pattern of signs and symptoms. The most common and severe form of the disease is the classic type, which becomes apparent soon after birth. Variant forms of the disorder become apparent later in infancy or childhood and are typically milder, but they still involve developmental delay and other medical problems if not treated.
Maple syrup urine disease 1B: A metabolic disorder due to an enzyme defect in the catabolic pathway of the branched-chain amino acids leucine, isoleucine, and valine. Accumulation of these 3 amino acids and their corresponding keto acids leads to encephalopathy and progressive neurodegeneration. Clinical features include mental and physical retardation, feeding problems, and a maple syrup odor to the urine. The keto acids of the branched- chain amino acids are present in the urine. If untreated, maple syrup urine disease can lead to seizures, coma, and death. The disease is often classified by its pattern of signs and symptoms. The most common and severe form of the disease is the classic type, which becomes apparent soon after birth. Variant forms of the disorder become apparent later in infancy or childhood and are typically milder, but they still involve developmental delay and other medical problems if not treated.
Maple syrup urine disease 2: A metabolic disorder due to an enzyme defect in the catabolic pathway of the branched-chain amino acids leucine, isoleucine, and valine. Accumulation of these 3 amino acids and their corresponding keto acids leads to encephalopathy and progressive neurodegeneration. Clinical features include mental and physical retardation, feeding problems, and a maple syrup odor to the urine. The keto acids of the branched- chain amino acids are present in the urine. If untreated, maple syrup urine disease can lead to seizures, coma, and death. The disease is often classified by its pattern of signs and symptoms. The most common and severe form of the disease is the classic type, which becomes apparent soon after birth. Variant forms of the disorder become apparent later in infancy or childhood and are typically milder, but they still involve developmental delay and other medical problems if not treated.

MalaCards based summary : Maple Syrup Urine Disease, also known as bckd deficiency, is related to intermediate maple syrup urine disease and amino acid metabolic disorder, and has symptoms including seizures, vomiting and ataxia. An important gene associated with Maple Syrup Urine Disease is BCKDHB (Branched Chain Keto Acid Dehydrogenase E1 Subunit Beta), and among its related pathways/superpathways are Valine, leucine and isoleucine degradation and Metabolism. The drugs 4-phenylbutyric acid and Mango have been mentioned in the context of this disorder. Affiliated tissues include brain, liver and testes, and related phenotypes are intellectual disability and global developmental delay

Disease Ontology : 12 An organic acidemia that is caused by a deficiency of decarboxylase leading to high concentrations of valine, leucine, isoleucine, and alloisoleucine in the blood, urine, and cerebrospinal fluid and characterized by an odor of maple syrup to the urine, vomiting, hypertonicity, severe mental retardation, seizures, and eventually death unless the condition is treated with dietary measures.

Genetics Home Reference : 25 Maple syrup urine disease is an inherited disorder in which the body is unable to process certain protein building blocks (amino acids) properly. The condition gets its name from the distinctive sweet odor of affected infants' urine. It is also characterized by poor feeding, vomiting, lack of energy (lethargy), abnormal movements, and delayed development. If untreated, maple syrup urine disease can lead to seizures, coma, and death. Maple syrup urine disease is often classified by its pattern of signs and symptoms. The most common and severe form of the disease is the classic type, which becomes apparent soon after birth. Variant forms of the disorder become apparent later in infancy or childhood and are typically milder, but they still lead to delayed development and other health problems if not treated.

NIH Rare Diseases : 52 Maple syrup urine disease is an inherited disorder in which the body is unable to process certain protein building blocks (amino acids ) properly. Beginning in early infancy, this condition is characterized by poor feeding, vomiting, lack of energy (lethargy), seizures , and developmental delay . The urine of affected infants has a distinctive sweet odor, much like burned caramel, that gives the condition its name. Maple syrup urine disease can be life-threatening if untreated.

OMIM : 56 The major clinical features of maple syrup urine disease are mental and physical retardation, feeding problems, and a maple syrup odor to the urine. The keto acids of the branched-chain amino acids are present in the urine, resulting from a block in oxidative decarboxylation. There are 5 clinical subtypes of MSUD: the 'classic' neonatal severe form, an 'intermediate' form, an 'intermittent' form, a 'thiamine-responsive' form, and an 'E3-deficient with lactic acidosis' form (246900). All of these subtypes can be caused by mutations in any of the 4 genes mentioned above, except for the E3-deficient form, which is caused only by mutation in the E3 gene (Chuang and Shih, 2001). (248600)

KEGG : 36 Maple syrup urine disease (MSUD) is an autosomal recessive inherited disorder caused by a defect in the oxidative decarboxylation of branched-chain amino acids (BCAA) leading to mental and physical retardation, feeding problems, and a maple syrup odor to the urine. Currently, there are effective therapies that are in use for MSUD; the dietary therapy and thiamin supplementation. The dietary therapy, which involves feeding patients with a synthetic diet containing reduced BCAA contents.

Wikipedia : 74 Maple syrup urine disease (MSUD) is an autosomal recessive metabolic disorder affecting branched-chain... more...

GeneReviews: NBK1319

Related Diseases for Maple Syrup Urine Disease

Diseases in the Maple Syrup Urine Disease family:

Intermediate Maple Syrup Urine Disease

Diseases related to Maple Syrup Urine Disease via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 183)
# Related Disease Score Top Affiliating Genes
1 intermediate maple syrup urine disease 35.2 PPM1K DBT BCKDHB BCKDHA
2 amino acid metabolic disorder 32.3 PRODH OTC MMD BTD BCKDHB BCKDHA
3 enteropathica 31.6 OTC ALB
4 inherited metabolic disorder 31.5 PRODH MMD ALB
5 brain edema 31.4 OTC GFAP ALB
6 metabolic acidosis 31.3 OGDH HMGCL BTD ALB
7 phenylketonuria 31.1 SLC7A5 QDPR PRODH OTC HADHA BTD
8 tyrosinemia 31.0 QDPR OTC BTD
9 methylmalonic acidemia 30.9 PRODH OTC MMD BCKDHB
10 homocystinuria 30.7 OTC MMD HMGCL HADHA BTD ALB
11 propionic acidemia 30.7 OTC MMD HMGCL HADHA BCKDK BCKDHB
12 citrullinemia, classic 30.7 OTC MMD HADHA BCKDHB
13 primary biliary cirrhosis 30.6 OGDH DLD DBT ALB
14 urea cycle disorder 30.6 PRODH OTC MMD ALB
15 organic acidemia 30.3 PRODH PPM1K MMD HMGCL BTD BCKDK
16 maple syrup urine disease, mild variant 13.2
17 dihydrolipoamide dehydrogenase deficiency 12.8
18 disorder of branched-chain amino acid metabolism 11.3
19 autosomal recessive disease 10.9
20 encephalopathy 10.8
21 ocular motor apraxia 10.8
22 ataxia and polyneuropathy, adult-onset 10.7
23 hypoglycemia 10.7
24 acrodermatitis 10.6
25 acrodermatitis enteropathica, zinc-deficiency type 10.6
26 hypotonia 10.6
27 alpha-ketoglutarate dehydrogenase deficiency 10.5 OGDH DLD
28 glioma 10.5
29 kearns-sayre syndrome 10.5
30 diarrhea 10.5
31 cerebral palsy 10.5
32 dystonia 10.5
33 glial tumor 10.5
34 blind loop syndrome 10.5 OTC ALB
35 pyruvate dehydrogenase e1-alpha deficiency 10.4
36 thiamine metabolism dysfunction syndrome 2 10.4 QDPR BTD
37 alacrima, achalasia, and mental retardation syndrome 10.4
38 gastroenteritis 10.4
39 dermatitis 10.4
40 pancreatitis 10.4
41 aminoacidopathies 10.4
42 spasticity 10.4
43 branched-chain keto acid dehydrogenase kinase deficiency 10.4 PPM1K DLD BCKDK BCKDHB BCKDHA
44 spinal cord disease 10.4 GFAP BTD ALB
45 ornithine transcarbamylase deficiency, hyperammonemia due to 10.4 OTC MMD BCKDHB
46 pyridoxamine 5-prime-phosphate oxidase deficiency 10.4 QDPR BTD
47 lysinuric protein intolerance 10.3 SLC7A5 PRODH OTC
48 pyrimidine metabolic disorder 10.3 PRODH OTC
49 cerebral degeneration 10.3 PRODH GFAP ALB
50 triiodothyronine receptor auxiliary protein 10.3

Graphical network of the top 20 diseases related to Maple Syrup Urine Disease:



Diseases related to Maple Syrup Urine Disease

Symptoms & Phenotypes for Maple Syrup Urine Disease

Human phenotypes related to Maple Syrup Urine Disease:

58 31 (show all 26)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 58 31 hallmark (90%) Very frequent (99-80%) HP:0001249
2 global developmental delay 58 31 hallmark (90%) Very frequent (99-80%) HP:0001263
3 muscular hypotonia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001252
4 respiratory insufficiency 58 31 hallmark (90%) Very frequent (99-80%) HP:0002093
5 reduced tendon reflexes 58 31 hallmark (90%) Very frequent (99-80%) HP:0001315
6 abnormality of the voice 58 31 hallmark (90%) Very frequent (99-80%) HP:0001608
7 abnormality of the pharynx 58 31 hallmark (90%) Very frequent (99-80%) HP:0000600
8 elevated plasma branched chain amino acids 58 31 hallmark (90%) Very frequent (99-80%) HP:0008344
9 seizure 31 hallmark (90%) HP:0001250
10 ataxia 58 31 frequent (33%) Frequent (79-30%) HP:0001251
11 hemiplegia/hemiparesis 58 31 frequent (33%) Frequent (79-30%) HP:0004374
12 hallucinations 31 HP:0000738
13 seizures 58 Very frequent (99-80%)
14 hypertonia 31 HP:0001276
15 feeding difficulties in infancy 31 HP:0008872
16 vomiting 31 HP:0002013
17 hypoglycemia 31 HP:0001943
18 lethargy 31 HP:0001254
19 lactic acidosis 31 HP:0003128
20 generalized hypotonia 31 HP:0001290
21 pancreatitis 31 HP:0001733
22 coma 31 HP:0001259
23 cerebral edema 31 HP:0002181
24 ketosis 31 HP:0001946
25 growth abnormality 31 HP:0001507
26 increased level of hippuric acid in urine 31 HP:0410066

Symptoms via clinical synopsis from OMIM:

56
Neurologic Central Nervous System:
hallucinations
seizures
hypertonia
ataxia
lethargy
more
Metabolic Features:
hypoglycemia
ketosis
life-threatening metabolic decompensation
lactic acidosis in e3-deficiency

Laboratory Abnormalities:
elevated plasma branched chain amino acids (leucine, isoleucine, valine)
maple syrup urine odor
branched chain ketoaciduria (alpha-keto isocaproate, alpha-keto-beta methylisovalerate, alpha-keto isovalerate)
elevated plasma alloisoleucine
positive urine dnph screening test

Abdomen Gastrointestinal:
vomiting
feeding problems

Abdomen Pancreas:
pancreatitis

Clinical features from OMIM:

248600

UMLS symptoms related to Maple Syrup Urine Disease:


seizures, vomiting, ataxia, headache, lethargy, cyanosis, dyspnea on exertion

GenomeRNAi Phenotypes related to Maple Syrup Urine Disease according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00107-A-1 9.81 BCKDK
2 Decreased viability GR00221-A-2 9.81 BCKDK
3 Decreased viability GR00221-A-3 9.81 BCKDK
4 Decreased viability GR00240-S-1 9.81 DLD HIBADH
5 Decreased viability GR00249-S 9.81 ALB BCAT2 BCKDHB BCKDK DLD HIBADH
6 Decreased viability GR00381-A-1 9.81 BCAT2 BCKDHA GFAP PRODH
7 Decreased viability GR00386-A-1 9.81 ALB BCKDHA HADHA HIBADH HMGCL OGDH
8 Decreased viability GR00402-S-2 9.81 BCKDHA BCKDK GFAP LAMB1 OGDH SLC7A5

MGI Mouse Phenotypes related to Maple Syrup Urine Disease:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10.1 BCAT2 BCKDHA BCKDK BTD DBT GFAP
2 homeostasis/metabolism MP:0005376 10.03 ALB BCAT2 BCKDHA BCKDK BTD DBT
3 mortality/aging MP:0010768 9.86 ALB BCAT2 BCKDHA BCKDHB BCKDK DBT
4 renal/urinary system MP:0005367 9.17 ALB BCAT2 BCKDK BTD DBT HADHA

Drugs & Therapeutics for Maple Syrup Urine Disease

Drugs for Maple Syrup Urine Disease (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 13)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1 4-phenylbutyric acid Phase 2, Phase 3
2 Mango Approved
3
Caffeine Approved 58-08-2 2519
4
tannic acid Approved 1401-55-4
5
Benzocaine Approved, Investigational 94-09-7, 1994-09-7 2337
6 Tea
7 Olive
8 Insulin, Globin Zinc
9 insulin
10 Calamus
11 Central Nervous System Stimulants
12 Phosphodiesterase Inhibitors
13 Neurotransmitter Agents

Interventional clinical trials:

(show all 14)
# Name Status NCT ID Phase Drugs
1 A Double-Blind, Randomized, Placebo-Controlled, Crossover Trial of Phenylbutyrate in the Treatment of Maple Syrup Urine Disease Completed NCT01529060 Phase 2, Phase 3 Phenylbutyrate;Placebo powder
2 An Open-Label, Pilot Study of a Red Blood Cell Precursor Formulation to Determine Increased Production in Subjects With Mild to Moderate Anemia Withdrawn NCT01701531 Phase 2, Phase 3 RBCPF
3 Medical Nutrition Therapy in Gestational Diabetes Mellitus: Comparison of Different Number of Meals. A Pilot Study Unknown status NCT03378908
4 Effects of Ketonemia and Glycemia Variations During Ketogenic and Mediterranean Weight Loss Diets on Appetite Levels, Executive Functions and Mood Completed NCT04086498
5 Optimisation of Acute Medium Chain Triglycerides Intake Characteristics on Different Plasma Metabolites in Young and Older Participants Completed NCT03830268
6 Effect of Medium-chain Triglycerides Emulsification on Ketogenesis and Adverse Effects in Human Adults Completed NCT02409927
7 Impact of Ketone Bodies on Myocardial Glucose and Fatty Acid Metabolism in Healthy Volunteers: A Positron Emission Tomography Study Completed NCT02814474 Early Phase 1
8 OptiDiag: Biomedical Investigations for Optimized Diagnosis and Monitoring of Severe Acute Malnutrition (SAM): Elucidating the Heterogeneous Diagnosis of SAM by Current Anthropometric Criteria and Moving Beyond Completed NCT03400930
9 Educational, Social Support, and Nutritional Interventions and Their Cumulative Effect on Pregnancy Outcomes and Quality of Life in Teen and Adult Women With Phenylketonuria (PKU) or Maple Syrup Urine Disease (MSUD). Recruiting NCT01659749
10 Identification and Validation of Relevant Patient and Observer Reported Outcome Measurements in Inborn Errors of Metabolism Recruiting NCT04248062
11 EtCO2 for Monitoring and Predicting Severity of DKA in Pediatric Emergency, Doha, Qatar. Recruiting NCT04121572
12 The Effect of Exogenous Ketone Supplementation on 20 km Time Trial and Wingate Performance in Recreationally Active Individuals Recruiting NCT03895892
13 Effect of Ketone Supplementation on Glycogen Replenishment and Time Trial Performance Following Glycogen Lowering Exercise Recruiting NCT04004676
14 Observational Study to Evaluate the Relationship Between Ketonemia and Renal Function in the Diabetic Patient Active, not recruiting NCT03859817

Search NIH Clinical Center for Maple Syrup Urine Disease

Cochrane evidence based reviews: maple syrup urine disease

Genetic Tests for Maple Syrup Urine Disease

Genetic tests related to Maple Syrup Urine Disease:

# Genetic test Affiliating Genes
1 Maple Syrup Urine Disease Type 1a 29
2 Maple Syrup Urine Disease 29 BCKDHA BCKDHB DBT
3 Maple Syrup Urine Disease Type 1b 29
4 Maple Syrup Urine Disease Type 2 29
5 Classical Maple Syrup Urine Disease 29

Anatomical Context for Maple Syrup Urine Disease

MalaCards organs/tissues related to Maple Syrup Urine Disease:

40
Brain, Liver, Testes, Cortex, Skin, Whole Blood, Heart

Publications for Maple Syrup Urine Disease

Articles related to Maple Syrup Urine Disease:

(show top 50) (show all 1150)
# Title Authors PMID Year
1
Molecular and structural analyses of maple syrup urine disease and identification of a founder mutation in a Portuguese Gypsy community. 6 24 56 61
18378174 2008
2
Structural and biochemical basis for novel mutations in homozygous Israeli maple syrup urine disease patients: a proposed mechanism for the thiamin-responsive phenotype. 6 56 24 61
14742428 2004
3
Molecular basis of intermittent maple syrup urine disease: novel mutations in the E2 gene of the branched-chain alpha-keto acid dehydrogenase complex. 61 56 54 6
9621512 1998
4
Molecular basis of maple syrup urine disease: novel mutations at the E1 alpha locus that impair E1(alpha 2 beta 2) assembly or decrease steady-state E1 alpha mRNA levels of branched-chain alpha-keto acid dehydrogenase complex. 6 61 54 56
8037208 1994
5
Revisiting MSUD in Portuguese Gypsies: evidence for a founder mutation and for a mutational hotspot within the BCKDHA gene. 61 56 6
19456321 2009
6
Description of the mutations in 15 subjects with variant forms of maple syrup urine disease. 61 24 56 54
17922217 2007
7
Molecular and biochemical basis of intermediate maple syrup urine disease. Occurrence of homozygous G245R and F364C mutations at the E1 alpha locus of Hispanic-Mexican patients. 61 56 6
7883996 1995
8
Molecular defects in the E1 alpha subunit of the branched-chain alpha-ketoacid dehydrogenase complex that cause maple syrup urine disease. 56 6 61
1943689 1991
9
Molecular genetic basis of maple syrup urine disease in a family with two defective alleles for branched chain acyltransferase and localization of the gene to human chromosome 1. 6 56 61
1990841 1991
10
A T-to-A substitution in the E1 alpha subunit gene of the branched-chain alpha-ketoacid dehydrogenase complex in two cell lines derived from Menonite maple syrup urine disease patients. 56 6 61
2241958 1990
11
Evidence for both a regulatory mutation and a structural mutation in a family with maple syrup urine disease. 61 56 6
2703538 1989
12
Nutrition management guideline for maple syrup urine disease: an evidence- and consensus-based approach. 61 24 6
24881969 2014
13
Relationship of causative genetic mutations in maple syrup urine disease with their clinical expression. 61 56 24
14567968 2003
14
Genetic heritage of the Old Order Mennonites of southeastern Pennsylvania. 6 24 61
12888983 2003
15
Maple syrup urine disease: identification and carrier-frequency determination of a novel founder mutation in the Ashkenazi Jewish population. 24 61 56
11509994 2001
16
Whole-body L-leucine oxidation in patients with variant form of maple syrup urine disease. 61 56 24
11328944 2001
17
Branched-chain L-amino acid metabolism in classical maple syrup urine disease after orthotopic liver transplantation. 61 24 56
11196106 2000
18
4,5-dimethyl-3-hydroxy-2[5H]-furanone (sotolone)--the odour of maple syrup urine disease. 61 56 24
10234605 1999
19
Case reports of successful pregnancy in women with maple syrup urine disease and propionic acidemia. 56 24 61
1481826 1992
20
Occurrence of a Tyr393----Asn (Y393N) mutation in the E1 alpha gene of the branched-chain alpha-keto acid dehydrogenase complex in maple syrup urine disease patients from a Mennonite population. 6 61 24
1867199 1991
21
Maple syrup urine disease in the Austronesian aboriginal tribe Paiwan of Taiwan: a novel DBT (E2) gene 4.7 kb founder deletion caused by a nonhomologous recombination between LINE-1 and Alu and the carrier-frequency determination. 61 54 6
14508502 2003
22
Diagnosis and treatment of maple syrup disease: a study of 36 patients. 24 56
12042535 2002
23
Occurrence of a 2-bp (AT) deletion allele and a nonsense (G-to-T) mutant allele at the E2 (DBT) locus of six patients with maple syrup urine disease: multiple-exon skipping as a secondary effect of the mutations. 6 54 61
8430702 1993
24
Maple syrup urine disease caused by a partial deletion in the inner E2 core domain of the branched chain alpha-keto acid dehydrogenase complex due to aberrant splicing. A single base deletion at a 5'-splice donor site of an intron of the E2 gene disrupts the consensus sequence in this region. 61 54 6
2010537 1991
25
A 17-bp insertion and a Phe215----Cys missense mutation in the dihydrolipoyl transacylase (E2) mRNA from a thiamine-responsive maple syrup urine disease patient WG-34. 54 56 61
1847055 1991
26
A novel regulatory defect in the branched-chain α-keto acid dehydrogenase complex due to a mutation in the PPM1K gene causes a mild variant phenotype of maple syrup urine disease. 61 6
23086801 2013
27
Mutational spectrum of maple syrup urine disease in Spain. 54 24 61
16786533 2006
28
Maple Syrup Urine Disease 61 6
20301495 2006
29
ENU mutagenesis identifies mice with mitochondrial branched-chain aminotransferase deficiency resembling human maple syrup urine disease. 56 61
14755340 2004
30
Disturbance of cultured rat neuronal network activity depends on concentration and ratio of leucine and alpha-ketoisocaproate: implication for acute encephalopathy of maple syrup urine disease. 61 56
12538793 2003
31
Gene preference in maple syrup urine disease. 56 61
11112664 2001
32
False diagnosis of maple syrup urine disease owing to ingestion of herbal tea. 61 56
10475807 1999
33
Impaired assembly of E1 decarboxylase of the branched-chain alpha-ketoacid dehydrogenase complex in type IA maple syrup urine disease. 6 61
9582350 1998
34
Fenugreek odour in maple syrup urine disease. 61 56
9266407 1997
35
Mammalian alpha-keto acid dehydrogenase complexes: gene regulation and genetic defects. 61 56
7672509 1995
36
Gene analysis of Mennonite maple syrup urine disease kindred using primer-specified restriction map modification. 61 6
1356170 1992
37
Maple syrup urine disease in Mennonites. Evidence that the Y393N mutation in E1 alpha impedes assembly of the E1 component of branched-chain alpha-keto acid dehydrogenase complex. 6 61
1885764 1991
38
Maple syrup urine disease. Complete defect of the E1 beta subunit of the branched chain alpha-ketoacid dehydrogenase complex due to a deletion of an 11-bp repeat sequence which encodes a mitochondrial targeting leader peptide in a family with the disease. 61 56
2022752 1991
39
Maple syrup urine disease: domain structure, mutations and exon skipping in the dihydrolipoyl transacylase (E2) component of the branched-chain alpha-keto acid dehydrogenase complex. 54 61 24
1943690 1991
40
Sequence of the E1 alpha subunit of branched-chain alpha-ketoacid dehydrogenase in two patients with thiamine-responsive maple syrup urine disease. 56 61
2316528 1990
41
Molecular phenotypes in cultured maple syrup urine disease cells. Complete E1 alpha cDNA sequence and mRNA and subunit contents of the human branched chain alpha-keto acid dehydrogenase complex. 56 61
2914958 1989
42
Maple syrup urine disease: a possible biochemical basis for the clinical heterogeneity. 56 61
3417306 1988
43
So-called thiamin-responsive maple syrup urine disease: 15-year follow-up of the original patient. 61 56
4056978 1985
44
Absence of branched chain acyl-transferase as a cause of maple syrup urine disease. 61 56
3980729 1985
45
A distinct variant of intermediate maple syrup urine disease. 56 61
3978850 1985
46
Maple syrup urine disease: two different forms within a single family. 61 56
4029957 1985
47
Thiamine-responsive inborn errors of metabolism. 56 61
3930844 1985
48
Maple-syrup-urine disease. 61 56
6694715 1984
49
Complementation analysis in lymphoid cells from five patients with different forms of maple syrup urine disease. 61 56
6500555 1984
50
Outcome of maple syrup urine disease. 61 56
7181520 1982

Variations for Maple Syrup Urine Disease

ClinVar genetic disease variations for Maple Syrup Urine Disease:

6 (show top 50) (show all 634) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 DBT NM_001918.4(DBT):c.902G>A (p.Arg301His)SNV Pathogenic 437447 rs770981889 1:100680410-100680410 1:100214854-100214854
2 DBT NC_000001.11:g.(?_100196235)_(100196442_?)deldeletion Pathogenic 457141 1:100661791-100661998 1:100196235-100196442
3 BCKDHB NM_183050.4(BCKDHB):c.348del (p.Asp117fs)deletion Pathogenic 457148 rs1400121541 6:80877396-80877396 6:80167679-80167679
4 BCKDHB NM_183050.4(BCKDHB):c.503G>A (p.Arg168His)SNV Pathogenic 457149 rs749033513 6:80878617-80878617 6:80168900-80168900
5 BCKDHA NM_000709.4(BCKDHA):c.143del (p.Leu48fs)deletion Pathogenic 522650 rs1555765593 19:41916576-41916576 19:41410671-41410671
6 BCKDHB NM_183050.4(BCKDHB):c.714dup (p.Glu239Ter)duplication Pathogenic 527130 rs1167005638 6:80881073-80881074 6:80171356-80171357
7 BCKDHB NM_183050.4(BCKDHB):c.152del (p.Val51fs)deletion Pathogenic 527129 rs867612284 6:80816562-80816562 6:80106845-80106845
8 BCKDHA NM_000709.4(BCKDHA):c.859C>T (p.Arg287Ter)SNV Pathogenic 553989 rs764247545 19:41928539-41928539 19:41422634-41422634
9 BCKDHA NM_000709.4(BCKDHA):c.718del (p.Ala240fs)deletion Pathogenic 558389 rs1555766993 19:41928136-41928136 19:41422231-41422231
10 BCKDHB NM_183050.4(BCKDHB):c.57_64dup (p.His22fs)duplication Pathogenic 568561 rs1410520713 6:80816460-80816461 6:80106743-80106744
11 BCKDHB NM_183050.4(BCKDHB):c.564T>A (p.Cys188Ter)SNV Pathogenic 580585 rs774306610 6:80878678-80878678 6:80168961-80168961
12 BCKDHA NM_000709.4(BCKDHA):c.332T>C (p.Leu111Pro)SNV Pathogenic 623384 rs1568503938 19:41916871-41916871 19:41410966-41410966
13 BCKDHA NM_000709.4(BCKDHA):c.554del (p.Leu185fs)deletion Pathogenic 623332 rs1568506608 19:41925108-41925108 19:41419203-41419203
14 DBT NM_001918.4(DBT):c.663_670del (p.Lys222fs)deletion Pathogenic 623328 rs748851630 1:100681641-100681648 1:100216085-100216092
15 BCKDHA NM_000709.4(BCKDHA):c.1069C>T (p.Gln357Ter)SNV Pathogenic 634552 rs762199542 19:41928976-41928976 19:41423071-41423071
16 DBT NM_001918.4(DBT):c.261del (p.Glu88fs)deletion Pathogenic 657974 1:100696461-100696461 1:100230905-100230905
17 BCKDHB NM_183050.4(BCKDHB):c.70_71insTTCCTGGCAGGGGCTGAGGA (p.Arg24delinsLeuProGlyArgGlyTer)insertion Pathogenic 653956 6:80816480-80816481 6:80106763-80106764
18 DBT NM_001918.4(DBT):c.898del (p.Ala300fs)deletion Pathogenic 635310 1:100680414-100680414 1:100214858-100214858
19 DBT NM_001918.4(DBT):c.1082dup (p.Asn361fs)duplication Pathogenic 801528 1:100672127-100672128 1:100206571-100206572
20 BCKDHA NC_000019.10:g.(?_41397818)_(41414167_?)deldeletion Pathogenic 832142 19:41903723-41920072
21 DBT NC_000001.11:g.(?_100196245)_(100196432_?)deldeletion Pathogenic 830477 1:100661801-100661988
22 DBT NC_000001.11:g.(?_100214807)_(100230924_?)deldeletion Pathogenic 831148 1:100680363-100696480
23 DBT NC_000001.11:g.(?_100240741)_(100240904_?)deldeletion Pathogenic 831115 1:100706297-100706460
24 DBT NC_000001.11:g.(?_100240751)_(100240894_?)deldeletion Pathogenic 830385 1:100706307-100706450
25 BCKDHB NC_000006.12:g.(?_80106674)_(80106909_?)deldeletion Pathogenic 832004 6:80816391-80816626
26 BCKDHB NC_000006.12:g.(?_80200924)_(80201041_?)deldeletion Pathogenic 831655 6:80910641-80910758
27 BCKDHB NM_183050.4(BCKDHB):c.583dup (p.Tyr195fs)duplication Pathogenic 838288 6:80878696-80878697 6:80168979-80168980
28 BCKDHB NM_183050.4(BCKDHB):c.908dup (p.Asp303fs)duplication Pathogenic 849015 6:80912885-80912886 6:80203168-80203169
29 BCKDHA NM_000709.4(BCKDHA):c.929C>G (p.Thr310Arg)SNV Pathogenic 2381 rs137852875 19:41928609-41928609 19:41422704-41422704
30 BCKDHA NM_000709.4(BCKDHA):c.792C>G (p.Cys264Trp)SNV Pathogenic 2382 rs137852876 19:41928214-41928214 19:41422309-41422309
31 BCKDHA BCKDHA, 1-BP DEL, 117Cdeletion Pathogenic 2383
32 BCKDHA NM_000709.4(BCKDHA):c.1226T>G (p.Phe409Cys)SNV Pathogenic 2378 rs137852872 19:41930401-41930401 19:41424496-41424496
33 DBT NM_001918.3:c.48_171deldeletion Pathogenic 11942
34 DBT NM_001918.4(DBT):c.1017+1deldeletion Pathogenic 11945 rs796052134 1:100676249-100676249 1:100210693-100210693
35 DBT NM_001918.3(DBT):c.1282-4142_*(434_435)deldeletion Pathogenic 11951 1:100661376-100666120 1:100195820-100200564
36 DBT NM_001918.4(DBT):c.581C>G (p.Ser194Ter)SNV Pathogenic 11953 rs121965003 1:100681730-100681730 1:100216174-100216174
37 BCKDHA NM_000709.4(BCKDHA):c.117del (p.Arg40fs)deletion Pathogenic 93342 rs398123489 19:41916544-41916544 19:41410639-41410639
38 DBT NM_001918.4(DBT):c.670G>T (p.Glu224Ter)SNV Pathogenic 94009 rs74103423 1:100681641-100681641 1:100216085-100216085
39 BCKDHB NM_183050.4(BCKDHB):c.633+1G>ASNV Pathogenic 96602 rs398124589 6:80878748-80878748 6:80169031-80169031
40 BCKDHB NM_183050.4(BCKDHB):c.1016C>T (p.Ser339Leu)SNV Pathogenic 96563 rs398124561 6:80982916-80982916 6:80273199-80273199
41 BCKDHB NM_183050.4(BCKDHB):c.593_594AG[1] (p.Ser199_Pro200insTer)short repeat Pathogenic 96599 rs398124587 6:80878707-80878708 6:80168990-80168991
42 BCKDHB NM_183050.4(BCKDHB):c.748G>T (p.Glu250Ter)SNV Pathogenic 96607 rs398124592 6:80910656-80910656 6:80200939-80200939
43 BCKDHB NM_183050.4(BCKDHB):c.82_92GGCGCGGGGCT[1] (p.Ala32fs)short repeat Pathogenic 96618 rs398124601 6:80816490-80816500 6:80106773-80106783
44 BCKDHA NM_000709.4(BCKDHA):c.117dup (p.Arg40fs)duplication Pathogenic 166741 rs398123489 19:41916543-41916544 19:41410638-41410639
45 BCKDHA NM_000709.4(BCKDHA):c.861_868del (p.Gly288fs)deletion Pathogenic 198433 rs794727847 19:41928539-41928546 19:41422634-41422641
46 BCKDHA NM_000709.4(BCKDHA):c.661_664del (p.Tyr221fs)deletion Pathogenic 203638 rs796051938 19:41928081-41928084 19:41422176-41422179
47 BCKDHA NM_000709.4(BCKDHA):c.470A>C (p.Gln157Pro)SNV Pathogenic 204380 rs869312125 19:41920048-41920048 19:41414143-41414143
48 BCKDHA NM_000709.4(BCKDHA):c.476G>A (p.Arg159Gln)SNV Pathogenic 204378 rs773048903 19:41920054-41920054 19:41414149-41414149
49 BCKDHA NM_000709.4(BCKDHA):c.844G>C (p.Asp282His)SNV Pathogenic 204377 rs869312124 19:41928266-41928266 19:41422361-41422361
50 BCKDHB NM_183050.4(BCKDHB):c.401T>A (p.Ile134Asn)SNV Pathogenic 224060 rs869312130 6:80877452-80877452 6:80167735-80167735

UniProtKB/Swiss-Prot genetic disease variations for Maple Syrup Urine Disease:

73 (show all 19)
# Symbol AA change Variation ID SNP ID
1 BCKDHA p.Arg159Trp VAR_004968 rs769688327
2 BCKDHA p.Gln190Lys VAR_004969
3 BCKDHA p.Ala253Thr VAR_004970 rs199599175
4 BCKDHA p.Ile326Thr VAR_004971
5 BCKDHA p.Tyr413Cys VAR_004972
6 BCKDHA p.Tyr438Asn VAR_004973 rs137852870
7 BCKDHA p.Gly290Arg VAR_015101 rs137852871
8 BCKDHA p.Phe409Cys VAR_015102 rs137852872
9 BCKDHA p.Thr211Met VAR_069748 rs398123503
10 BCKDHA p.Ala220Val VAR_069749 rs375785084
11 BCKDHA p.Arg346Cys VAR_069750 rs182923857
12 BCKDHB p.His206Arg VAR_004974
13 BCKDHB p.Arg183Pro VAR_024851 rs79761867
14 BCKDHB p.Gly278Ser VAR_024852 rs386834233
15 BCKDHB p.Arg170His VAR_068348 rs371518124
16 BCKDHB p.Gln346Arg VAR_068349
17 DBT p.Phe276Cys VAR_004978 rs121964999
18 DBT p.Ile98Met VAR_015099 rs121965001
19 DBT p.Gly384Ser VAR_015100 rs12021720

Expression for Maple Syrup Urine Disease

Search GEO for disease gene expression data for Maple Syrup Urine Disease.

Pathways for Maple Syrup Urine Disease

Pathways related to Maple Syrup Urine Disease according to KEGG:

36
# Name Kegg Source Accession
1 Valine, leucine and isoleucine degradation hsa00280

Pathways related to Maple Syrup Urine Disease according to GeneCards Suite gene sharing:

(show all 11)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.74 SLC7A5 QDPR PRODH PPM1K OTC OGDH
2
Show member pathways
13.58 SLC7A5 QDPR PRODH PPM1K OTC OGDH
3
Show member pathways
12.2 OTC OGDH HADHA DLD BCAT2
4
Show member pathways
11.94 SLC7A5 QDPR PRODH OGDH DLD
5 11.79 OTC OGDH HMGCL HIBADH DLD
6
Show member pathways
11.63 OGDH HADHA DLD
7
Show member pathways
11.4 PPM1K HMGCL HIBADH HADHA DLD DBT
8
Show member pathways
11.2 OGDH DLD DBT BCKDHB BCKDHA
9
Show member pathways
11.1 DLD DBT BCKDHB BCKDHA
10 10.89 HADHA DLD DBT BCKDHB BCKDHA
11
Show member pathways
10.62 DLD DBT BCKDHB BCKDHA

GO Terms for Maple Syrup Urine Disease

Cellular components related to Maple Syrup Urine Disease according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.97 PRODH PPM1K OTC OGDH HMGCL HIBADH
2 mitochondrial matrix GO:0005759 9.44 PRODH PPM1K OTC OGDH HMGCL HIBADH
3 oxoglutarate dehydrogenase complex GO:0045252 9.26 OGDH DLD
4 mitochondrial alpha-ketoglutarate dehydrogenase complex GO:0005947 9.26 DBT BCKDK BCKDHB BCKDHA

Biological processes related to Maple Syrup Urine Disease according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 oxidation-reduction process GO:0055114 9.56 QDPR PRODH OGDH HIBADH HADHA DLD
2 liver development GO:0001889 9.5 QDPR OTC HMGCL
3 2-oxoglutarate metabolic process GO:0006103 9.37 OGDH DLD
4 lysine catabolic process GO:0006554 9.26 OGDH DLD
5 branched-chain amino acid catabolic process GO:0009083 9.23 PPM1K HIBADH DLD DBT BCKDK BCKDHB
6 histone succinylation GO:0106077 9.16 OGDH DLD

Molecular functions related to Maple Syrup Urine Disease according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 catalytic activity GO:0003824 9.77 PPM1K HMGCL HADHA BCKDHB BCAT2
2 NAD binding GO:0051287 9.43 HIBADH HADHA DLD
3 fatty-acyl-CoA binding GO:0000062 9.4 HMGCL HADHA
4 oxidoreductase activity, acting on the aldehyde or oxo group of donors, disulfide as acceptor GO:0016624 9.32 OGDH BCKDHA
5 oxidoreductase activity GO:0016491 9.23 QDPR PRODH OGDH HIBADH HADHA DLD
6 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring) activity GO:0003863 9.16 BCKDHB BCKDHA
7 alpha-ketoacid dehydrogenase activity GO:0003826 8.96 BCKDHB BCKDHA

Sources for Maple Syrup Urine Disease

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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