Thiamine-responsive maple syrup urine disease

General Information (adopted from Orphanet):

Synonyms, Signs: BRANCHED-CHAIN KETOACIDURIA
MAPLE SYRUP URINE DISEASE, THIAMINE-RESPONSIVE, INCLUDED
MSUD2, INCLUDED
MAPLE SYRUP URINE DISEASE, INTERMITTENT, INCLUDED
MSUD1A, INCLUDED
MAPLE SYRUP URINE DISEASE, TYPE II, INCLUDED
MAPLE SYRUP URINE DISEASE, TYPE IA, INCLUDED
MAPLE SYRUP URINE DISEASE, INTERMEDIATE, INCLUDED
BRANCHED-CHAIN ALPHA-KETO ACID DEHYDROGENASE DEFICIENCY
MAPLE SYRUP URINE DISEASE, TYPE IB, INCLUDED
KETO ACID DECARBOXYLASE DEFICIENCY MAPLE SYRUP URINE DISEASE, CLASSIC, INCLUDED
MSUD1B, INCLUDED
BCKD DEFICIENCY
MSUD
Thiamine-responsive MSUD
Thiamine-responsive leucinosis
Thiamine-responsive branched-chain ketoaciduria
Thiamine-responsive branched-chain ketoacid dehydrogenase deficiency
Thiamine-responsive BCKD deficiency
Number of Symptoms 26
OrphanetNr: 268184
OMIM Id: 248600
ICD-10: E71.0
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Autosomal recessive
[Orphanet]
Age of onset: Neonatal
Infancy
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: Maple syrup urine disease
 -Rare genetic disease

Symptom Information: Sort by abundance 

1
(HPO:0001259) Coma 65 / 7739
2
(HPO:0001250) Seizures 1245 / 7739
3
(HPO:0000738) Hallucinations 60 / 7739
4
(HPO:0001276) Hypertonia 317 / 7739
5
(HPO:0001251) Ataxia 413 / 7739
6
(HPO:0001254) Lethargy 104 / 7739
7
(HPO:0002013) Vomiting 191 / 7739
8
(HPO:0011968) Feeding difficulties 240 / 7739
9
(HPO:0001733) Pancreatitis 46 / 7739
10
(HPO:0008344) Elevated plasma branched chain amino acids 5 / 7739
11
(HPO:0002181) Cerebral edema 19 / 7739
12
(HPO:0001946) Ketosis 17 / 7739
13
(HPO:0001943) Hypoglycemia 131 / 7739
14
(HPO:0001252) Muscular hypotonia 990 / 7739
15
(HPO:0001324) Muscle weakness 859 / 7739
16
(HPO:0008947) Infantile muscular hypotonia 482 / 7739
17
(HPO:0010547) Muscle flaccidity 466 / 7739
18
(OMIM) Mental retardation if untreated 5 / 7739
19
(OMIM) White matter signal abnormalities in various brain regions 3 / 7739
20
(OMIM) Lactic acidosis in E3-deficiency 3 / 7739
21
(OMIM) Positive urine DNPH screening test 3 / 7739
22
(OMIM) Brain MRI shows diffusion abnormalities 3 / 7739
23
(OMIM) Life-threatening metabolic decompensation 3 / 7739
24
(OMIM) Maple syrup urine odor 3 / 7739
25
(OMIM) Elevated plasma alloisoleucine 3 / 7739
26
(OMIM) Branched chain ketoaciduria (alpha-keto isocaproate, alpha-keto-beta methylisovalerate, alpha-keto isovalerate) 3 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) 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 ...
Clinical Description OMIM - Classic Severe MSUD

Menkes et al. (1954) reported a familial syndrome in which 4 sibs had progressive infantile cerebral dysfunction associated with an unusual urinary substance. Onset was in the first week of life, with ...

Genotype-Phenotype Correlations OMIM Nellis et al. (2003) evaluated and compared the clinical course of 11 unrelated patients with MSUD, including 3 with mutations in the E1-alpha gene, 5 with mutations in the E1-beta gene, and 3 with mutations in the E2 ...
Molecular genetics OMIM - Mutations in the E1-alpha Subunit Gene

In a patient with classic MSUD, Zhang et al. (1989,1991) identified a mutation in the gene encoding the E1-alpha subunit (608348.0001). Chuang et al. (1994) later identified a second ...

Population genetics OMIM In a mobile, urban, predominantly white population of New England, Levy (1973) found a frequency of MSUD of 1 in 290,000 on newborn screening. The highest reported frequency of MSUD was observed among the Old Order Mennonites of ...