MSUD
MCID: MPL001
MIFTS: 68

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 57 12 75 24 53 25 59 74 37 29 55 6 44 15 40 72
Bckd Deficiency 57 24 53 25 59 74
Msud 57 24 53 25 59 74
Branched-Chain Ketoaciduria 57 24 25 59 74
Branched-Chain Alpha-Keto Acid Dehydrogenase Deficiency 57 53 25 74
Intermittent Maple Syrup Urine Disease 59 74 72
Keto Acid Decarboxylase Deficiency 57 53 74
Maple Syrup Urine Disease, Type Ii 57 13 72
Maple Syrup Urine Disease Type 1a 53 29 6
Maple Syrup Urine Disease Type 1b 53 29 6
Classic Maple Syrup Urine Disease 59 74 72
Maple Syrup Urine Disease Type 2 53 29 6
Thiamine-Responsive Maple Syrup Urine Disease 59 74
Intermediate Maple Syrup Urine Disease 74 72
Maple Syrup Urine Disease, Type Ia 57 72
Branched Chain Ketoaciduria 12 53
Msud Type Ib 53 74
Msud2 53 74
Msud Due to Deficiency of E1-Beta Subunit of Branched-Chain Alpha-Keto Acid Dehydrogenase Complex 53
Thiamine-Responsive Branched-Chain Alpha-Ketoacid Dehydrogenase Deficiency 59
Intermittent Branched-Chain Alpha-Ketoacid Dehydrogenase Deficiency 59
Classic Branched-Chain Alpha-Ketoacid Dehydrogenase Deficiency 59
Lactic Acidosis, Congenital Infantile, Due to Lad Deficiency 72
Branched-Chain 2-Ketoacid Dehydrogenase Deficiency 59
Branched-Chain Ketoacid Dehydrogenase Deficiency 24
Dihydrolipoamide Dehydrogenase Deficiency 12
Nadh Cytochrome B5 Reductase Deficiency 72
Classic Branched-Chain Ketoaciduria 59
Thiamine-Responsive Bckd Deficiency 59
Classical Maple Syrup Urine Disease 29
Maple Syrup Urine Disease, Type Ib 57
Maple Syrup Urine Disease, Type 1b 72
Maple Syrup Urine Disease Type Ia 74
Maple Syrup Urine Disease Type Ib 74
Maple Syrup Urine Disease Type Ii 74
Intermittent Bckd Deficiency 59
Maple Syrup Urine Disease 1a 74
Maple Syrup Urine Disease 1b 74
Maple Syrup Urine Disease 2 74
Thiamine-Responsive Msud 59
Classic Bckd Deficiency 59
Maple Syrup Disease 24
Intermittent Msud 59
Bckdh Deficiency 59
Ketoacidaemia 12
Msud Type 1a 53
Ketoacidemia 25
Classic Msud 59
Msud Type Ia 74
Msud Type Ii 74
Msud Type 2 53
Ketonemia 72
Msud1a 74
Msud1b 74

Characteristics:

Orphanet epidemiological data:

59
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
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:

32
maple syrup urine disease:
Inheritance autosomal recessive inheritance
Onset and clinical course recurrent


Classifications:

Orphanet: 59  
Inborn errors of metabolism


External Ids:

Disease Ontology 12 DOID:9269
KEGG 37 H00172
MeSH 44 D008375
NCIt 50 C34806
SNOMED-CT 68 27718001
ICD10 33 E71.0
MESH via Orphanet 45 D008375
ICD10 via Orphanet 34 E71.0
UMLS via Orphanet 73 C0024776 C0268568 C0268569 more
UMLS 72 C0024776 C0235430 C0268193 more

Summaries for Maple Syrup Urine Disease

UniProtKB/Swiss-Prot : 74 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 enteropathica, 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 Mango have been mentioned in the context of this disorder. Affiliated tissues include brain, liver and testes, and related phenotypes are intellectual disability and seizures

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 : 53 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 : 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)

KEGG : 37
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 : 75 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 157)
# Related Disease Score Top Affiliating Genes
1 intermediate maple syrup urine disease 34.8 PPM1K DBT BCKDHB BCKDHA
2 enteropathica 30.9 OTC ALB
3 acrodermatitis 30.9 OTC ALB
4 brain edema 30.5 OTC GFAP ALB
5 phenylketonuria 30.0 OTC HADHA BTD
6 organic acidemia 29.9 HMGCL BTD BCKDHB BCKDHA
7 maple syrup urine disease, mild variant 13.2
8 dihydrolipoamide dehydrogenase deficiency 12.8
9 amino acid metabolic disorder 11.9
10 disorder of branched-chain amino acid metabolism 11.3
11 autosomal recessive disease 10.9
12 inherited metabolic disorder 10.9
13 encephalopathy 10.9
14 ocular motor apraxia 10.8
15 hydrops, lactic acidosis, and sideroblastic anemia 10.7
16 ataxia and polyneuropathy, adult-onset 10.7
17 metabolic acidosis 10.6
18 hypoglycemia 10.6
19 acrodermatitis enteropathica, zinc-deficiency type 10.6
20 hypotonia 10.6
21 homocystinuria 10.5
22 glioma 10.5
23 kearns-sayre syndrome 10.5
24 diarrhea 10.5
25 dystonia 10.5
26 glial tumor 10.5
27 pyruvate dehydrogenase e1-alpha deficiency 10.4
28 cerebral palsy 10.4
29 gastroenteritis 10.4
30 pancreatitis 10.4
31 aminoacidopathies 10.4
32 spasticity 10.4
33 pyuria 10.4 BCKDHA ALB
34 meningitis and encephalitis 10.4 CAT ALB
35 triiodothyronine receptor auxiliary protein 10.3
36 galactosemia 10.3
37 yemenite deaf-blind hypopigmentation syndrome 10.3
38 propionic acidemia 10.3
39 anxiety 10.3
40 alacrima, achalasia, and mental retardation syndrome 10.3
41 congenital hypothyroidism 10.3
42 respiratory failure 10.3
43 hepatitis a 10.3
44 polyneuropathy 10.3
45 hypothyroidism 10.3
46 methylmalonic acidemia 10.3
47 dermatitis 10.3
48 astrocytoma 10.3
49 grade iii astrocytoma 10.3
50 neuropathy 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:

59 32 (show all 25)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 59 32 hallmark (90%) Very frequent (99-80%) HP:0001249
2 seizures 59 32 hallmark (90%) Very frequent (99-80%) HP:0001250
3 muscular hypotonia 59 32 hallmark (90%) Very frequent (99-80%) HP:0001252
4 respiratory insufficiency 59 32 hallmark (90%) Very frequent (99-80%) HP:0002093
5 global developmental delay 59 32 hallmark (90%) Very frequent (99-80%) HP:0001263
6 reduced tendon reflexes 59 32 hallmark (90%) Very frequent (99-80%) HP:0001315
7 abnormality of the voice 59 32 hallmark (90%) Very frequent (99-80%) HP:0001608
8 abnormality of the pharynx 59 32 hallmark (90%) Very frequent (99-80%) HP:0000600
9 elevated plasma branched chain amino acids 59 32 hallmark (90%) Very frequent (99-80%) HP:0008344
10 ataxia 59 32 frequent (33%) Frequent (79-30%) HP:0001251
11 hemiplegia/hemiparesis 59 32 frequent (33%) Frequent (79-30%) HP:0004374
12 hallucinations 32 HP:0000738
13 hypertonia 32 HP:0001276
14 feeding difficulties in infancy 32 HP:0008872
15 vomiting 32 HP:0002013
16 hypoglycemia 32 HP:0001943
17 generalized hypotonia 32 HP:0001290
18 pancreatitis 32 HP:0001733
19 lactic acidosis 32 HP:0003128
20 coma 32 HP:0001259
21 lethargy 32 HP:0001254
22 cerebral edema 32 HP:0002181
23 ketosis 32 HP:0001946
24 growth abnormality 32 HP:0001507
25 increased level of hippuric acid in urine 32 HP:0410066

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
seizures
ataxia
hallucinations
hypertonia
coma
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, ataxia, vomiting, headache, lethargy, cyanosis, dyspnea on exertion

MGI Mouse Phenotypes related to Maple Syrup Urine Disease:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 10.07 ALB BCAT2 BCKDK BTD CAT CHKB
2 behavior/neurological MP:0005386 10.02 BCAT2 BCKDK BTD CHKB DBT DLST
3 mortality/aging MP:0010768 9.93 ALB BCAT2 BCKDK CAT DBT DLD
4 muscle MP:0005369 9.5 ALB BCKDK BTD CHKB GFAP HADHA
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 11)
# 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 insulin
7 Insulin, Globin Zinc
8 Neurotransmitter Agents
9 Central Nervous System Stimulants
10 Purinergic P1 Receptor Antagonists
11 Phosphodiesterase Inhibitors

Interventional clinical trials:

(show all 11)
# 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 Effect of Medium-chain Triglycerides Emulsification on Ketogenesis and Adverse Effects in Human Adults Completed NCT02409927
4 Impact of Ketone Bodies on Myocardial Glucose and Fatty Acid Metabolism in Healthy Volunteers: A Positron Emission Tomography Study Completed NCT02814474 Early Phase 1
5 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
6 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
7 Medical Nutrition Therapy in Gestational Diabetes Mellitus: Comparison of Different Number of Meals. A Pilot Study Recruiting NCT03378908
8 Optimisation of Acute Medium Chain Triglycerides Intake Characteristics on Different Plasma Metabolites in Young and Older Participants Recruiting NCT03830268
9 The Effect of Exogenous Ketone Supplementation on 20 km Time Trial and Wingate Performance in Recreationally Active Individuals Recruiting NCT03895892
10 Observational Study to Evaluate the Relationship Between Ketonemia and Renal Function in the Diabetic Patient Active, not recruiting NCT03859817
11 Effect of Ketone Supplementation on Glycogen Replenishment and Time Trial Performance Following Glycogen Lowering Exercise Not yet recruiting NCT04004676

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:

41
Brain, Liver, Testes, Cortex, Skin, Heart, Whole Blood

Publications for Maple Syrup Urine Disease

Articles related to Maple Syrup Urine Disease:

(show top 50) (show all 1129)
# 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. 38 4 8 71
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. 38 4 8 71
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. 9 38 8 71
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. 9 38 8 71
8037208 1994
5
Revisiting MSUD in Portuguese Gypsies: evidence for a founder mutation and for a mutational hotspot within the BCKDHA gene. 38 8 71
19456321 2009
6
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. 38 8 71
7883996 1995
7
Molecular defects in the E1 alpha subunit of the branched-chain alpha-ketoacid dehydrogenase complex that cause maple syrup urine disease. 38 8 71
1943689 1991
8
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. 38 8 71
1990841 1991
9
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. 38 8 71
2241958 1990
10
Evidence for both a regulatory mutation and a structural mutation in a family with maple syrup urine disease. 38 8 71
2703538 1989
11
Relationship of causative genetic mutations in maple syrup urine disease with their clinical expression. 38 4 8
14567968 2003
12
Genetic heritage of the Old Order Mennonites of southeastern Pennsylvania. 38 4 71
12888983 2003
13
Whole-body L-leucine oxidation in patients with variant form of maple syrup urine disease. 38 4 8
11328944 2001
14
Gene preference in maple syrup urine disease. 38 4 8
11112664 2001
15
Branched-chain L-amino acid metabolism in classical maple syrup urine disease after orthotopic liver transplantation. 38 4 8
11196106 2000
16
4,5-dimethyl-3-hydroxy-2[5H]-furanone (sotolone)--the odour of maple syrup urine disease. 38 4 8
10234605 1999
17
Case reports of successful pregnancy in women with maple syrup urine disease and propionic acidemia. 38 4 8
1481826 1992
18
Description of the mutations in 15 subjects with variant forms of maple syrup urine disease. 9 38 8
17922217 2007
19
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. 9 38 71
14508502 2003
20
Diagnosis and treatment of maple syrup disease: a study of 36 patients. 4 8
12042535 2002
21
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. 9 38 71
8430702 1993
22
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. 9 38 71
2010537 1991
23
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. 9 38 8
1847055 1991
24
Nutrition management guideline for maple syrup urine disease: an evidence- and consensus-based approach. 38 71
24881969 2014
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. 38 71
23086801 2013
26
Mutational spectrum of maple syrup urine disease in Spain. 9 38 4
16786533 2006
27
Maple Syrup Urine Disease 38 71
20301495 2006
28
ENU mutagenesis identifies mice with mitochondrial branched-chain aminotransferase deficiency resembling human maple syrup urine disease. 38 8
14755340 2004
29
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. 38 8
12538793 2003
30
Maple syrup urine disease: identification and carrier-frequency determination of a novel founder mutation in the Ashkenazi Jewish population. 38 8
11509994 2001
31
False diagnosis of maple syrup urine disease owing to ingestion of herbal tea. 38 8
10475807 1999
32
Impaired assembly of E1 decarboxylase of the branched-chain alpha-ketoacid dehydrogenase complex in type IA maple syrup urine disease. 38 71
9582350 1998
33
Fenugreek odour in maple syrup urine disease. 38 8
9266407 1997
34
Mammalian alpha-keto acid dehydrogenase complexes: gene regulation and genetic defects. 38 8
7672509 1995
35
Gene analysis of Mennonite maple syrup urine disease kindred using primer-specified restriction map modification. 38 71
1356170 1992
36
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. 38 71
1885764 1991
37
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. 38 71
1867199 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. 38 8
2022752 1991
39
Sequence of the E1 alpha subunit of branched-chain alpha-ketoacid dehydrogenase in two patients with thiamine-responsive maple syrup urine disease. 38 8
2316528 1990
40
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. 38 8
2914958 1989
41
Maple syrup urine disease: a possible biochemical basis for the clinical heterogeneity. 38 8
3417306 1988
42
So-called thiamin-responsive maple syrup urine disease: 15-year follow-up of the original patient. 38 8
4056978 1985
43
Absence of branched chain acyl-transferase as a cause of maple syrup urine disease. 38 8
3980729 1985
44
A distinct variant of intermediate maple syrup urine disease. 38 8
3978850 1985
45
Maple syrup urine disease: two different forms within a single family. 38 8
4029957 1985
46
Thiamine-responsive inborn errors of metabolism. 38 8
3930844 1985
47
Maple-syrup-urine disease. 38 8
6694715 1984
48
Complementation analysis in lymphoid cells from five patients with different forms of maple syrup urine disease. 38 8
6500555 1984
49
Outcome of maple syrup urine disease. 38 8
7181520 1982
50
Prospective study of maple-syrup-urine disease for the first four days of life. 38 8
7144815 1982

Variations for Maple Syrup Urine Disease

ClinVar genetic disease variations for Maple Syrup Urine Disease:

6 (show top 50) (show all 459)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 BCKDHB NM_000056.4(BCKDHB): c.487G> T (p.Glu163Ter) single nucleotide variant Pathogenic rs1057516799 6:80878601-80878601 6:80168884-80168884
2 BCKDHA NM_000709.4(BCKDHA): c.399delinsAA (p.Asn134fs) indel Pathogenic rs1057519059 19:41919977-41919977 19:41414072-41414072
3 DBT NM_001918.4(DBT): c.902G> A (p.Arg301His) single nucleotide variant Pathogenic rs770981889 1:100680410-100680410 1:100214854-100214854
4 DBT NC_000001.10: g.(?_100661791)_(100661998_?)del deletion Pathogenic 1:100661791-100661998 1:100196235-100196442
5 BCKDHB NM_000056.4(BCKDHB): c.348del (p.Asp117fs) deletion Pathogenic rs1400121541 6:80877399-80877399 6:80167682-80167682
6 BCKDHB NM_000056.4(BCKDHB): c.503G> A (p.Arg168His) single nucleotide variant Pathogenic rs749033513 6:80878617-80878617 6:80168900-80168900
7 BCKDHA NM_000709.4(BCKDHA): c.143del (p.Leu48fs) deletion Pathogenic rs1555765593 19:41916576-41916576 19:41410671-41410671
8 BCKDHB NM_000056.4(BCKDHB): c.152del (p.Val51fs) deletion Pathogenic rs867612284 6:80816562-80816562 6:80106845-80106845
9 BCKDHB NM_000056.4(BCKDHB): c.714dup (p.Glu239Ter) duplication Pathogenic rs1167005638 6:80881079-80881079 6:80171362-80171362
10 BCKDHA NM_000709.4(BCKDHA): c.859C> T (p.Arg287Ter) single nucleotide variant Pathogenic rs764247545 19:41928539-41928539 19:41422634-41422634
11 BCKDHA NM_000709.4(BCKDHA): c.718del (p.Ala240fs) deletion Pathogenic rs1555766993 19:41928135-41928136 19:41422235-41422235
12 BCKDHA NM_000709.4(BCKDHA): c.745G> A (p.Gly249Ser) single nucleotide variant Pathogenic rs137852874 19:41928167-41928167 19:41422262-41422262
13 BCKDHA NM_000709.4(BCKDHA): c.1226T> G (p.Phe409Cys) single nucleotide variant Pathogenic rs137852872 19:41930401-41930401 19:41424496-41424496
14 BCKDHA NM_000709.4(BCKDHA): c.929C> G (p.Thr310Arg) single nucleotide variant Pathogenic rs137852875 19:41928609-41928609 19:41422704-41422704
15 BCKDHA NM_000709.4(BCKDHA): c.792C> G (p.Cys264Trp) single nucleotide variant Pathogenic rs137852876 19:41928214-41928214 19:41422309-41422309
16 BCKDHA BCKDHA, 1-BP DEL, 117C deletion Pathogenic
17 DBT NM_001918.3: c.48_171del deletion Pathogenic
18 DBT NM_001918.3(DBT): c.940_1017del deletion Pathogenic rs796052134 1:100676249-100676249 1:100210693-100210693
19 DBT NM_001918.3(DBT): c.1282-4142_*(434_435)del deletion Pathogenic 1:100661376-100666120 1:100195820-100200564
20 DBT NM_001918.4(DBT): c.581C> G (p.Ser194Ter) single nucleotide variant Pathogenic rs121965003 1:100681730-100681730 1:100216174-100216174
21 BCKDHA NM_000709.4(BCKDHA): c.117del (p.Arg40fs) deletion Pathogenic rs398123489 19:41916550-41916550 19:41410645-41410645
22 BCKDHB NM_000056.4(BCKDHB): c.82_92GGCGCGGGGCT[1] (p.Ala32fs) short repeat Pathogenic rs398124601 6:80816503-80816513 6:80106786-80106796
23 BCKDHB NM_000056.4(BCKDHB): c.593_594AG[1] (p.Ser199_Pro200insTer) short repeat Pathogenic rs398124587 6:80878709-80878710 6:80168992-80168993
24 BCKDHB NM_000056.4(BCKDHB): c.633+1G> A single nucleotide variant Pathogenic rs398124589 6:80878748-80878748 6:80169031-80169031
25 BCKDHA NM_000709.4(BCKDHA): c.661_664del (p.Tyr221fs) deletion Pathogenic rs796051938 19:41928083-41928086 19:41422178-41422181
26 BCKDHA NM_000709.4(BCKDHA): c.470A> C (p.Gln157Pro) single nucleotide variant Pathogenic rs869312125 19:41920048-41920048 19:41414143-41414143
27 BCKDHA NM_000709.4(BCKDHA): c.476G> A (p.Arg159Gln) single nucleotide variant Pathogenic rs773048903 19:41920054-41920054 19:41414149-41414149
28 BCKDHA NM_000709.4(BCKDHA): c.844G> C (p.Asp282His) single nucleotide variant Pathogenic rs869312124 19:41928266-41928266 19:41422361-41422361
29 BCKDHB NM_000056.4(BCKDHB): c.401T> A (p.Ile134Asn) single nucleotide variant Pathogenic rs869312130 6:80877452-80877452 6:80167735-80167735
30 BCKDHB NM_000056.4(BCKDHB): c.554C> T (p.Pro185Leu) single nucleotide variant Pathogenic rs148905512 6:80878668-80878668 6:80168951-80168951
31 BCKDHB NM_000056.4(BCKDHB): c.964A> G (p.Thr322Ala) single nucleotide variant Pathogenic rs869312131 6:80982864-80982864 6:80273147-80273147
32 BCKDHB NM_000056.4(BCKDHB): c.1065del (p.Pro356fs) deletion Pathogenic rs869312129 6:81053407-81053407 6:80343690-80343690
33 DBT NM_001918.4(DBT): c.1033G> A (p.Gly345Arg) single nucleotide variant Pathogenic rs869312132 1:100672177-100672177 1:100206621-100206621
34 BCKDHA NM_000709.4(BCKDHA): c.940C> T (p.Arg314Ter) single nucleotide variant Pathogenic rs753698250 19:41928620-41928620 19:41422715-41422715
35 BCKDHB NM_000056.4(BCKDHB): c.-66_196+1del deletion Pathogenic rs1554180622 6:80816345-80816607 6:80106627-80106889
36 BCKDHB NM_000056.4(BCKDHB): c.3G> A (p.Met1Ile) single nucleotide variant Pathogenic rs869312128 6:80816413-80816413 6:80106696-80106696
37 BCKDHB NM_000056.4(BCKDHB): c.197-2A> G single nucleotide variant Pathogenic rs869312127 6:80837262-80837262 6:80127545-80127545
38 BCKDHB NM_000056.4(BCKDHB): c.57_64dup (p.His22fs) duplication Pathogenic 6:80816467-80816474 6:80106750-80106757
39 BCKDHB NM_000056.4(BCKDHB): c.564T> A (p.Cys188Ter) single nucleotide variant Pathogenic 6:80878678-80878678 6:80168961-80168961
40 BCKDHA NM_000709.4(BCKDHA): c.332T> C (p.Leu111Pro) single nucleotide variant Pathogenic 19:41916871-41916871 19:41410966-41410966
41 BCKDHA NM_000709.4(BCKDHA): c.554del (p.Leu185fs) deletion Pathogenic 19:41925109-41925109 19:41419204-41419204
42 DBT NM_001918.4(DBT): c.663_670del (p.Lys222fs) deletion Pathogenic 1:100681641-100681648 1:100216085-100216092
43 BCKDHA NM_000709.4(BCKDHA): c.1069C> T (p.Gln357Ter) single nucleotide variant Pathogenic 19:41928976-41928976 19:41423071-41423071
44 DBT NM_001918.4(DBT): c.261del (p.Glu88fs) deletion Pathogenic 1:100696461-100696461 1:100230908-100230908
45 BCKDHB NM_000056.4(BCKDHB): c.70_71insTTCCTGGCAGGGGCTGAGGA (p.Arg24delinsLeuProGlyArgGlyTer) insertion Pathogenic 6:80816480-80816481 6:80106763-80106764
46 DBT NM_001918.4(DBT): c.898del (p.Ala300fs) deletion Pathogenic 1:100680414-100680414 1:100214858-100214858
47 BCKDHA NM_000709.4(BCKDHA): c.1198A> T (p.Lys400Ter) single nucleotide variant Pathogenic/Likely pathogenic rs863225262 19:41930373-41930373 19:41424468-41424468
48 DBT NM_001918.4(DBT): c.126T> G (p.Tyr42Ter) single nucleotide variant Pathogenic/Likely pathogenic rs794727262 1:100706366-100706366 1:100240810-100240810
49 BCKDHA NM_000709.4(BCKDHA): c.861_868del (p.Gly288fs) deletion Pathogenic/Likely pathogenic rs794727847 19:41928541-41928548 19:41422636-41422643
50 BCKDHB NM_000056.4(BCKDHB): c.1022T> A (p.Ile341Asn) single nucleotide variant Pathogenic/Likely pathogenic rs796051939 6:80982922-80982922 6:80273205-80273205

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

74 (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:

37
# 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 12)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.84 PPM1K OTC HMGCL HADHA DLST DLD
2
Show member pathways
13.53 PPM1K OTC DLST DLD DBT BCKDK
3
Show member pathways
12.17 OTC HADHA DLST DLD CAT BCAT2
4 11.69 OTC HMGCL DLST DLD
5
Show member pathways
11.36 HADHA DLD CHKB
6
Show member pathways
11.35 PPM1K HMGCL HADHA DLD DBT BCKDK
7
Show member pathways
11.27 DLST DLD DBT BCKDHB BCKDHA
8
Show member pathways
11.12 DLD DBT BCKDHB BCKDHA
9
Show member pathways
11.09 HMGCL HADHA
10 11.09 HADHA DLD DBT BCKDHB BCKDHA
11 10.97 DLD CAT
12
Show member pathways
10.26 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 9.9 PPM1K OTC HMGCL HADHA DLST DLD
2 mitochondrial matrix GO:0005759 9.36 PPM1K OTC HMGCL DLST DLD DBT
3 oxoglutarate dehydrogenase complex GO:0045252 9.26 DLST 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 9.77 HADHA DLD CAT BCKDHB BCKDHA
2 protein tetramerization GO:0051262 9.4 HMGCL CAT
3 response to insulin GO:0032868 9.33 OTC HADHA CAT
4 2-oxoglutarate metabolic process GO:0006103 9.32 DLST DLD
5 response to fatty acid GO:0070542 9.26 HMGCL CAT
6 branched-chain amino acid catabolic process GO:0009083 9.02 PPM1K BCKDK BCKDHB BCKDHA BCAT2
7 histone succinylation GO:0106077 8.96 DLST DLD

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

# Name GO ID Score Top Affiliating Genes
1 oxidoreductase activity GO:0016491 9.55 HADHA DLD CAT BCKDHB BCKDHA
2 antioxidant activity GO:0016209 9.32 CAT ALB
3 fatty-acyl-CoA binding GO:0000062 9.26 HMGCL HADHA
4 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring) activity GO:0003863 8.96 BCKDHB BCKDHA
5 alpha-ketoacid dehydrogenase activity GO:0003826 8.62 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 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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