MSUD
MCID: MPL001
MIFTS: 70

Maple Syrup Urine Disease (MSUD)

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

Aliases & Classifications for Maple Syrup Urine Disease

MalaCards integrated aliases for Maple Syrup Urine Disease:

Name: Maple Syrup Urine Disease 57 12 74 25 20 43 58 73 36 29 54 6 44 15 39 71
Bckd Deficiency 57 25 20 43 58 73
Msud 57 25 20 43 58 73
Branched-Chain Ketoaciduria 57 20 43 58 73
Branched-Chain Alpha-Keto Acid Dehydrogenase Deficiency 57 20 43 73
Intermittent Maple Syrup Urine Disease 58 73 71
Keto Acid Decarboxylase Deficiency 57 20 73
Maple Syrup Urine Disease, Type Ii 57 13 71
Classic Maple Syrup Urine Disease 58 73 71
Branched-Chain 2-Ketoacid Dehydrogenase Deficiency 20 58
Thiamine-Responsive Maple Syrup Urine Disease 58 73
Intermediate Maple Syrup Urine Disease 73 71
Maple Syrup Urine Disease, Type Ia 57 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 20
Bckdh Deficiency 20 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 25
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 57
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 25
Intermittent Msud 58
Ketoacidaemia 12
Ketoacidemia 43
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®:

57 (Updated 05-Mar-2021)
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® 57 248600
OMIM Phenotypic Series 57 PS248600
KEGG 36 H00172
MeSH 44 D008375
NCIt 50 C34806
SNOMED-CT 67 27718001
ICD10 32 E71.0
MESH via Orphanet 45 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 dihydrolipoamide dehydrogenase deficiency and intermediate maple syrup urine disease, and has symptoms including seizures, ataxia and vomiting. An important gene associated with Maple Syrup Urine Disease is BCKDHA (Branched Chain Keto Acid Dehydrogenase E1 Subunit Alpha), and among its related pathways/superpathways are Valine, leucine and isoleucine degradation and Metabolism. The drugs 4-phenylbutyric acid and carbamide peroxide have been mentioned in the context of this disorder. Affiliated tissues include brain, liver and cortex, and related phenotypes are intellectual disability and respiratory insufficiency

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.

MedlinePlus Genetics : 43 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.

GARD : 20 Maple syrup urine disease (MSUD) occurs when the body is unable to breakdown certain parts of proteins. This leads to the build-up of toxic substances that can cause organ and brain damage. There are several forms of MSUD. The most common is the classic or infantile form. Symptoms of the classic form of MSUD start in early infancy and include poor feeding, irritability, extra sleepiness, and muscle spasms. If untreated, respiratory failure (lack of oxygen getting to the blood) may occur. The earwax and urine of infants with MSUD smells like maple syrup. The symptoms of other forms of MSUD start in adolescence or adulthood. MSUD is caused by genetic variants in the BCKDHA, BCKDHB, or DBT genes. It is inherited in an autosomal recessive pattern. Diagnosis of MSUD is based on the symptoms, clinical exam, and blood and urine testing. MSUD is often diagnosed based on the results of a newborn screening test. Treatment includes a special protein restricted diet, supplements, and liver transplantation in some cases.

OMIM® : 57 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) (Updated 05-Mar-2021)

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 178)
# Related Disease Score Top Affiliating Genes
1 dihydrolipoamide dehydrogenase deficiency 33.2 DLD BCKDHB
2 intermediate maple syrup urine disease 33.1 PPM1K DBT BCKDHB BCKDHA
3 amino acid metabolic disorder 32.4 OTC BTD BCKDHB BCKDHA ALB
4 enteropathica 31.4 OTC ALB
5 phenylketonuria 31.4 SLC7A5 QDPR OTC HADHA CAT BTD
6 metabolic acidosis 31.3 OGDH HMGCL BTD ALB
7 brain edema 31.2 OTC GFAP ALB
8 homocystinuria 31.1 OTC HADHA BTD ALB
9 urea cycle disorder 30.9 OTC HADHA BCKDHB ALB
10 propionic acidemia 30.8 OTC HMGCL HADHA BCKDK BCKDHB BCKDHA
11 organic acidemia 30.8 PPM1K HMGCL BTD BCKDK BCKDHB BCKDHA
12 methylmalonic acidemia 30.8 OTC HMGCL HADHA BCKDHB BCKDHA
13 brain injury 30.7 GFAP ALB
14 citrullinemia, classic 30.7 OTC HADHA BCKDHB
15 wernicke encephalopathy 30.6 GFAP ALB
16 primary biliary cholangitis 30.6 OGDH DLD DBT ALB
17 maple syrup urine disease, mild variant 12.1
18 autosomal recessive disease 10.9
19 disorder of branched-chain amino acid metabolism 10.9
20 inherited metabolic disorder 10.8
21 encephalopathy 10.8
22 ocular motor apraxia 10.7
23 hypoglycemia 10.6
24 ataxia and polyneuropathy, adult-onset 10.6
25 acrodermatitis 10.6
26 acrodermatitis enteropathica, zinc-deficiency type 10.6
27 hypotonia 10.6
28 glioma 10.5
29 kearns-sayre syndrome 10.5
30 alacrima, achalasia, and mental retardation syndrome 10.5
31 cerebral palsy 10.5
32 dystonia 10.5
33 glial tumor 10.5
34 meningitis and encephalitis 10.4 CAT ALB
35 anxiety 10.4
36 gastroenteritis 10.4
37 dermatitis 10.4
38 pancreatitis 10.4
39 aminoacidopathies 10.4
40 spasticity 10.4
41 classic phenylketonuria 10.4
42 alpha-ketoglutarate dehydrogenase deficiency 10.4 OGDH DLST DLD
43 blind loop syndrome 10.4 OTC ALB
44 branched-chain keto acid dehydrogenase kinase deficiency 10.3 PPM1K DLD BCKDK BCKDHB BCKDHA
45 isovaleric acidemia 10.3 HADHA BTD BCKDHB
46 glycine encephalopathy 10.3 DLD BTD BCKDHB
47 reye syndrome 10.3 OTC HMGCL ALB
48 glioma susceptibility 1 10.3
49 triiodothyronine receptor auxiliary protein 10.3
50 galactosemia i 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 28)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 58 31 hallmark (90%) Very frequent (99-80%) HP:0001249
2 respiratory insufficiency 58 31 hallmark (90%) Very frequent (99-80%) HP:0002093
3 global developmental delay 58 31 hallmark (90%) Very frequent (99-80%) HP:0001263
4 reduced tendon reflexes 58 31 hallmark (90%) Very frequent (99-80%) HP:0001315
5 abnormality of the voice 58 31 hallmark (90%) Very frequent (99-80%) HP:0001608
6 abnormality of the pharynx 58 31 hallmark (90%) Very frequent (99-80%) HP:0000600
7 elevated plasma branched chain amino acids 58 31 hallmark (90%) Very frequent (99-80%) HP:0008344
8 seizure 31 hallmark (90%) HP:0001250
9 hypotonia 31 hallmark (90%) HP:0001252
10 ataxia 58 31 frequent (33%) Frequent (79-30%) HP:0001251
11 hemiplegia/hemiparesis 58 31 frequent (33%) Frequent (79-30%) HP:0004374
12 seizures 58 Very frequent (99-80%)
13 muscular hypotonia 58 Very frequent (99-80%)
14 hallucinations 31 HP:0000738
15 hypertonia 31 HP:0001276
16 feeding difficulties in infancy 31 HP:0008872
17 vomiting 31 HP:0002013
18 hypoglycemia 31 HP:0001943
19 lethargy 31 HP:0001254
20 lactic acidosis 31 HP:0003128
21 coma 31 HP:0001259
22 generalized hypotonia 31 HP:0001290
23 pancreatitis 31 HP:0001733
24 cerebral edema 31 HP:0002181
25 ketosis 31 HP:0001946
26 growth abnormality 31 HP:0001507
27 increased level of hippuric acid in urine 31 HP:0410066
28 elevated circulating l-alloisoleucine concentration 31 HP:0033155

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
Neurologic Central Nervous System:
seizures
ataxia
hallucinations
hypertonia
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 (Updated 05-Mar-2021)

UMLS symptoms related to Maple Syrup Urine Disease:


seizures, ataxia, vomiting, 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 9.8 BCKDK
2 Decreased viability GR00221-A-2 9.8 BCKDK
3 Decreased viability GR00221-A-3 9.8 BCKDK
4 Decreased viability GR00240-S-1 9.8 DLD HIBADH
5 Decreased viability GR00249-S 9.8 ALB BCAT2 BCKDHB BCKDK DLD HIBADH
6 Decreased viability GR00381-A-1 9.8 BCAT2 BCKDHA GFAP
7 Decreased viability GR00386-A-1 9.8 ALB BCKDHA DLST HADHA HIBADH HMGCL
8 Decreased viability GR00402-S-2 9.8 BCKDHA BCKDK GFAP LAMB1 OGDH SLC7A5

MGI Mouse Phenotypes related to Maple Syrup Urine Disease:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10.1 BCAT2 BCKDHA BCKDK BTD DBT DLST
2 homeostasis/metabolism MP:0005376 10.06 ALB BCAT2 BCKDHA BCKDK BTD CAT
3 growth/size/body region MP:0005378 10.03 BCAT2 BCKDHA BCKDHB BCKDK BTD DLD
4 mortality/aging MP:0010768 9.91 ALB BCAT2 BCKDHA BCKDHB BCKDK CAT
5 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 14)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1 4-phenylbutyric acid Phase 2, Phase 3
2
carbamide peroxide Approved 124-43-6
3
Caffeine Approved 58-08-2 2519
4
Benzocaine Approved, Investigational 1994-09-7, 94-09-7 2337
5
tannic acid Approved 1401-55-4
6
Ornithine Approved, Nutraceutical 70-26-8, 3184-13-2 6262
7 Tea
8 Olive
9 Insulin, Globin Zinc
10 insulin
11 carnitine
12 Central Nervous System Stimulants
13 Phosphodiesterase Inhibitors
14 Neurotransmitter Agents

Interventional clinical trials:


# 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 Identification and Validation of Relevant Patient and Observer Reported Outcome Measurements in Inborn Errors of Metabolism Completed NCT04248062
3 Effects of Ketonemia and Glycemia Variations During Ketogenic and Mediterranean Weight Loss Diets on Appetite Levels, Executive Functions and Mood Completed NCT04086498
4 Optimisation of Acute Medium Chain Triglycerides Intake Characteristics on Different Plasma Metabolites in Young and Older Participants Completed NCT03830268
5 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
6 Systemic Biomarkers of Brain Injury From Hyperammonemia Recruiting NCT04602325
7 The Effect of Exogenous Ketone Supplementation on 20 km Time Trial and Wingate Performance in Recreationally Active Individuals Recruiting NCT03895892
8 Effect of Ketone Supplementation on Glycogen Replenishment and Time Trial Performance Following Glycogen Lowering Exercise Recruiting NCT04004676
9 Observational Study to Evaluate the Relationship Between Ketonemia and Renal Function in the Diabetic Patient Active, not recruiting NCT03859817
10 Effect of Exogenous Ketone Supplementation on Cognitive Function During Exercise After Induced Mental Fatigue Not yet recruiting NCT04576026

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 BCKDHB
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, Cortex, Skin, Whole Blood, Heart, Cerebellum

Publications for Maple Syrup Urine Disease

Articles related to Maple Syrup Urine Disease:

(show top 50) (show all 1176)
# 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. 57 6 25 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. 25 6 57 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. 57 6 61 54
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. 57 6 61 54
8037208 1994
5
Revisiting MSUD in Portuguese Gypsies: evidence for a founder mutation and for a mutational hotspot within the BCKDHA gene. 61 6 57
19456321 2009
6
Description of the mutations in 15 subjects with variant forms of maple syrup urine disease. 61 57 25 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 57 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. 57 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. 61 57 6
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. 61 57 6
2241958 1990
11
Evidence for both a regulatory mutation and a structural mutation in a family with maple syrup urine disease. 57 6 61
2703538 1989
12
Relationship of causative genetic mutations in maple syrup urine disease with their clinical expression. 25 57 61
14567968 2003
13
Genetic heritage of the Old Order Mennonites of southeastern Pennsylvania. 61 25 6
12888983 2003
14
Maple syrup urine disease: identification and carrier-frequency determination of a novel founder mutation in the Ashkenazi Jewish population. 25 57 61
11509994 2001
15
Whole-body L-leucine oxidation in patients with variant form of maple syrup urine disease. 25 61 57
11328944 2001
16
Branched-chain L-amino acid metabolism in classical maple syrup urine disease after orthotopic liver transplantation. 57 61 25
11196106 2000
17
4,5-dimethyl-3-hydroxy-2[5H]-furanone (sotolone)--the odour of maple syrup urine disease. 25 61 57
10234605 1999
18
Case reports of successful pregnancy in women with maple syrup urine disease and propionic acidemia. 25 61 57
1481826 1992
19
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. 61 6 25
1867199 1991
20
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. 6 54 61
14508502 2003
21
Diagnosis and treatment of maple syrup disease: a study of 36 patients. 25 57
12042535 2002
22
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. 61 54 6
8430702 1993
23
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. 54 61 6
2010537 1991
24
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. 57 61 54
1847055 1991
25
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
26
Mutational spectrum of maple syrup urine disease in Spain. 25 54 61
16786533 2006
27
ENU mutagenesis identifies mice with mitochondrial branched-chain aminotransferase deficiency resembling human maple syrup urine disease. 57 61
14755340 2004
28
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. 57 61
12538793 2003
29
Gene preference in maple syrup urine disease. 57 61
11112664 2001
30
False diagnosis of maple syrup urine disease owing to ingestion of herbal tea. 57 61
10475807 1999
31
Impaired assembly of E1 decarboxylase of the branched-chain alpha-ketoacid dehydrogenase complex in type IA maple syrup urine disease. 6 61
9582350 1998
32
Fenugreek odour in maple syrup urine disease. 61 57
9266407 1997
33
Mammalian alpha-keto acid dehydrogenase complexes: gene regulation and genetic defects. 57 61
7672509 1995
34
Gene analysis of Mennonite maple syrup urine disease kindred using primer-specified restriction map modification. 6 61
1356170 1992
35
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
36
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 57
2022752 1991
37
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. 61 54 25
1943690 1991
38
Sequence of the E1 alpha subunit of branched-chain alpha-ketoacid dehydrogenase in two patients with thiamine-responsive maple syrup urine disease. 61 57
2316528 1990
39
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. 61 57
2914958 1989
40
Maple syrup urine disease: a possible biochemical basis for the clinical heterogeneity. 57 61
3417306 1988
41
So-called thiamin-responsive maple syrup urine disease: 15-year follow-up of the original patient. 57 61
4056978 1985
42
Absence of branched chain acyl-transferase as a cause of maple syrup urine disease. 57 61
3980729 1985
43
A distinct variant of intermediate maple syrup urine disease. 61 57
3978850 1985
44
Thiamine-responsive inborn errors of metabolism. 61 57
3930844 1985
45
Maple syrup urine disease: two different forms within a single family. 61 57
4029957 1985
46
Maple-syrup-urine disease. 61 57
6694715 1984
47
Complementation analysis in lymphoid cells from five patients with different forms of maple syrup urine disease. 57 61
6500555 1984
48
Outcome of maple syrup urine disease. 61 57
7181520 1982
49
Prospective study of maple-syrup-urine disease for the first four days of life. 61 57
7144815 1982
50
Detection of heterozygotes in maple-syrup-urine disease: measurements of branched-chain alpha-ketoacid dehydrogenase and its components in cell cultures. 61 57
7081220 1982

Variations for Maple Syrup Urine Disease

ClinVar genetic disease variations for Maple Syrup Urine Disease:

6 (show top 50) (show all 802)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 DBT NM_001918.4(DBT):c.294C>G (p.Ile98Met) SNV Pathogenic 11948 rs121965001 1:100696428-100696428 1:100230872-100230872
2 DBT NM_001918.4(DBT):c.1448G>T (p.Ter483Leu) SNV Pathogenic 11947 rs121965000 1:100661812-100661812 1:100196256-100196256
3 BCKDHA NM_000709.4(BCKDHA):c.861_868del (p.Gly288fs) Deletion Pathogenic 198433 rs794727847 19:41928539-41928546 19:41422634-41422641
4 BCKDHA NM_000709.4(BCKDHA):c.1226T>G (p.Phe409Cys) SNV Pathogenic 2378 rs137852872 19:41930401-41930401 19:41424496-41424496
5 BCKDHA NM_000709.4(BCKDHA):c.793C>T (p.Arg265Trp) SNV Pathogenic 2379 rs137852873 19:41928215-41928215 19:41422310-41422310
6 BCKDHA NM_000709.4(BCKDHA):c.745G>A (p.Gly249Ser) SNV Pathogenic 2380 rs137852874 19:41928167-41928167 19:41422262-41422262
7 BCKDHA NM_000709.4(BCKDHA):c.792C>G (p.Cys264Trp) SNV Pathogenic 2382 rs137852876 19:41928214-41928214 19:41422309-41422309
8 BCKDHA BCKDHA, 1-BP DEL, 117C Deletion Pathogenic 2383
9 DBT NM_001918.3:c.48_171del Deletion Pathogenic 11942
10 DBT NM_001918.4(DBT):c.1017+1del Deletion Pathogenic 11945 rs796052134 1:100676249-100676249 1:100210693-100210693
11 DBT NM_001918.5(DBT):c.1018-550A>G SNV Pathogenic 11946 rs796052135 1:100672742-100672742 1:100207186-100207186
12 DBT NM_001918.4(DBT):c.1150G>A (p.Gly384Ser) SNV Pathogenic 11949 rs12021720 1:100672060-100672060 1:100206504-100206504
13 DBT NM_001918.4(DBT):c.75_76del (p.Cys26fs) Deletion Pathogenic 11950 rs768832921 1:100706416-100706417 1:100240860-100240861
14 DBT NM_001918.3(DBT):c.1282-4142_*(434_435)del Deletion Pathogenic 11951 1:100661376-100666120 1:100195820-100200564
15 DBT NM_001918.4(DBT):c.581C>G (p.Ser194Ter) SNV Pathogenic 11953 rs121965003 1:100681730-100681730 1:100216174-100216174
16 BCKDHA NM_000709.4(BCKDHA):c.117del (p.Arg40fs) Deletion Pathogenic 93342 rs398123489 19:41916544-41916544 19:41410639-41410639
17 DBT NM_001918.4(DBT):c.670G>T (p.Glu224Ter) SNV Pathogenic 94009 rs74103423 1:100681641-100681641 1:100216085-100216085
18 BCKDHA NM_000709.4(BCKDHA):c.861_868del (p.Gly288fs) Deletion Pathogenic 198433 rs794727847 19:41928539-41928546 19:41422634-41422641
19 BCKDHA NM_000709.4(BCKDHA):c.940C>T (p.Arg314Ter) SNV Pathogenic 224072 rs753698250 19:41928620-41928620 19:41422715-41422715
20 DBT NM_001918.4(DBT):c.1033G>A (p.Gly345Arg) SNV Pathogenic 224073 rs869312132 1:100672177-100672177 1:100206621-100206621
21 BCKDHB NM_183050.4(BCKDHB):c.401T>A (p.Ile134Asn) SNV Pathogenic 224060 rs869312130 6:80877452-80877452 6:80167735-80167735
22 BCKDHA NM_000709.4(BCKDHA):c.470A>C (p.Gln157Pro) SNV Pathogenic 204380 rs869312125 19:41920048-41920048 19:41414143-41414143
23 BCKDHB NM_183050.4(BCKDHB):c.3G>A (p.Met1Ile) SNV Pathogenic 224057 rs869312128 6:80816413-80816413 6:80106696-80106696
24 BCKDHB NM_183050.4(BCKDHB):c.554C>T (p.Pro185Leu) SNV Pathogenic 224055 rs148905512 6:80878668-80878668 6:80168951-80168951
25 BCKDHA NM_000709.4(BCKDHA):c.844G>C (p.Asp282His) SNV Pathogenic 204377 rs869312124 19:41928266-41928266 19:41422361-41422361
26 BCKDHB NM_183050.4(BCKDHB):c.964A>G (p.Thr322Ala) SNV Pathogenic 224061 rs869312131 6:80982864-80982864 6:80273147-80273147
27 BCKDHB NM_183050.4(BCKDHB):c.1065del (p.Pro356fs) Deletion Pathogenic 224059 rs869312129 6:81053407-81053407 6:80343690-80343690
28 BCKDHB NM_183050.4(BCKDHB):c.197-2A>G SNV Pathogenic 224056 rs869312127 6:80837262-80837262 6:80127545-80127545
29 BCKDHB NM_000056.4(BCKDHB):c.-66_196+1del Deletion Pathogenic 224058 rs1554180622 6:80816344-80816606 6:80106627-80106889
30 BCKDHB NM_183050.4(BCKDHB):c.1022T>A (p.Ile341Asn) SNV Pathogenic 203639 rs796051939 6:80982922-80982922 6:80273205-80273205
31 BCKDHA NM_000709.4(BCKDHA):c.476G>A (p.Arg159Gln) SNV Pathogenic 204378 rs773048903 19:41920054-41920054 19:41414149-41414149
32 PPM1K PPM1K, 2-BP DEL, 417TA Deletion Pathogenic 41439
33 BCKDHB NM_183050.4(BCKDHB):c.487G>T (p.Glu163Ter) SNV Pathogenic 370827 rs1057516799 6:80878601-80878601 6:80168884-80168884
34 BCKDHA NM_000709.4(BCKDHA):c.399delinsAA (p.Asn134fs) Indel Pathogenic 374929 rs1057519059 19:41919977-41919977 19:41414072-41414072
35 DBT NM_001918.4(DBT):c.902G>A (p.Arg301His) SNV Pathogenic 437447 rs770981889 1:100680410-100680410 1:100214854-100214854
36 DBT NC_000001.11:g.(?_100196235)_(100196442_?)del Deletion Pathogenic 457141 1:100661791-100661998 1:100196235-100196442
37 BCKDHB NM_183050.4(BCKDHB):c.348del (p.Asp117fs) Deletion Pathogenic 457148 rs1400121541 6:80877396-80877396 6:80167679-80167679
38 BCKDHB NM_183050.4(BCKDHB):c.503G>A (p.Arg168His) SNV Pathogenic 457149 rs749033513 6:80878617-80878617 6:80168900-80168900
39 BCKDHB NM_183050.4(BCKDHB):c.82_92GGCGCGGGGCT[3] (p.Phe35fs) Microsatellite Pathogenic 189101 rs398124601 6:80816489-80816490 6:80106772-80106773
40 BCKDHA NM_000709.4(BCKDHA):c.143del (p.Leu48fs) Deletion Pathogenic 522650 rs1555765593 19:41916576-41916576 19:41410671-41410671
41 BCKDHB NM_183050.4(BCKDHB):c.152del (p.Val51fs) Deletion Pathogenic 527129 rs867612284 6:80816562-80816562 6:80106845-80106845
42 BCKDHB NM_183050.4(BCKDHB):c.714dup (p.Glu239Ter) Duplication Pathogenic 527130 rs1167005638 6:80881073-80881074 6:80171356-80171357
43 BCKDHA NM_000709.4(BCKDHA):c.859C>T (p.Arg287Ter) SNV Pathogenic 553989 rs764247545 19:41928539-41928539 19:41422634-41422634
44 BCKDHA NM_000709.4(BCKDHA):c.718del (p.Ala240fs) Deletion Pathogenic 558389 rs1555766993 19:41928136-41928136 19:41422231-41422231
45 BCKDHB NM_183050.4(BCKDHB):c.57_64dup (p.His22fs) Duplication Pathogenic 568561 rs1410520713 6:80816460-80816461 6:80106743-80106744
46 BCKDHB NM_183050.4(BCKDHB):c.564T>A (p.Cys188Ter) SNV Pathogenic 580585 rs774306610 6:80878678-80878678 6:80168961-80168961
47 DBT NM_001918.4(DBT):c.663_670del (p.Lys222fs) Deletion Pathogenic 623328 rs748851630 1:100681641-100681648 1:100216085-100216092
48 BCKDHA NM_000709.4(BCKDHA):c.554del (p.Leu185fs) Deletion Pathogenic 623332 rs1568506608 19:41925108-41925108 19:41419203-41419203
49 BCKDHA NM_000709.4(BCKDHA):c.332T>C (p.Leu111Pro) SNV Pathogenic 623384 rs1568503938 19:41916871-41916871 19:41410966-41410966
50 BCKDHB NM_183050.4(BCKDHB):c.487G>T (p.Glu163Ter) SNV Pathogenic 370827 rs1057516799 6:80878601-80878601 6:80168884-80168884

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 15)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.76 SLC7A5 QDPR PPM1K OTC OGDH HMGCL
2
Show member pathways
13.69 SLC7A5 QDPR PPM1K OTC OGDH HIBADH
3 12.33 SLC7A5 DLST CAT BCAT2
4
Show member pathways
12.28 OTC OGDH HADHA DLST DLD CAT
5
Show member pathways
11.98 SLC7A5 QDPR OGDH DLST DLD
6
Show member pathways
11.84 OGDH DLST DLD
7
Show member pathways
11.84 OGDH HADHA DLST DLD CAT
8 11.8 OTC OGDH HMGCL HIBADH DLST DLD
9
Show member pathways
11.71 OGDH DLST DLD
10 11.49 HADHA DLST DLD
11
Show member pathways
11.4 PPM1K HMGCL HIBADH HADHA DLD DBT
12 11.25 HADHA DLD DBT BCKDHB BCKDHA
13
Show member pathways
11.22 DLD DBT BCKDHB BCKDHA
14
Show member pathways
10.98 OGDH DLST DLD DBT BCKDHB BCKDHA
15 10.34 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 9.8 PPM1K OTC OGDH HMGCL HIBADH HADHA
2 mitochondrial alpha-ketoglutarate dehydrogenase complex GO:0005947 9.46 DBT BCKDK BCKDHB BCKDHA
3 mitochondrial matrix GO:0005759 9.44 PPM1K OTC OGDH HMGCL HIBADH DLST
4 oxoglutarate dehydrogenase complex GO:0045252 9.43 OGDH DLST DLD

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 9.76 QDPR OGDH HIBADH HADHA DLD CAT
2 liver development GO:0001889 9.61 QDPR OTC HMGCL
3 tricarboxylic acid cycle GO:0006099 9.54 OGDH DLST DLD
4 2-oxoglutarate metabolic process GO:0006103 9.5 OGDH DLST DLD
5 response to fatty acid GO:0070542 9.48 HMGCL CAT
6 response to lead ion GO:0010288 9.46 QDPR CAT
7 lysine catabolic process GO:0006554 9.43 OGDH DLST DLD
8 succinyl-CoA metabolic process GO:0006104 9.4 OGDH DLST
9 branched-chain amino acid catabolic process GO:0009083 9.23 PPM1K HIBADH DLD DBT BCKDK BCKDHB
10 histone succinylation GO:0106077 9.13 OGDH DLST 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 antioxidant activity GO:0016209 9.43 CAT ALB
3 NAD binding GO:0051287 9.43 HIBADH HADHA DLD
4 fatty-acyl-CoA binding GO:0000062 9.4 HMGCL HADHA
5 oxidoreductase activity, acting on the aldehyde or oxo group of donors, disulfide as acceptor GO:0016624 9.32 OGDH BCKDHA
6 oxidoreductase activity GO:0016491 9.23 QDPR OGDH HIBADH HADHA DLD CAT
7 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring) activity GO:0003863 9.16 BCKDHB BCKDHA
8 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
20 GARD
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
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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