MCID: THM010
MIFTS: 45

Thiamine Metabolism Dysfunction Syndrome 2

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

Aliases & Classifications for Thiamine Metabolism Dysfunction Syndrome 2

MalaCards integrated aliases for Thiamine Metabolism Dysfunction Syndrome 2:

Name: Thiamine Metabolism Dysfunction Syndrome 2 53 13
Biotin-Responsive Basal Ganglia Disease 12 55 71 36 14
Basal Ganglia Disease, Biotin-Responsive 53 28 69
Bbgd 53 55 71
Thiamine-Responsive Encephalopathy 55 71
Thmd2 53 71
Btbgd 53 55
Thiamine Metabolism Dysfunction Syndrome 2, Biotin- or Thiamine-Responsive Type 71
Biotin-Thiamine-Responsive Basal Ganglia Disease 55
Basal Ganglia Disease, Biotin-Responsive; Bbgd 53
Encephalopathy, Thiamine-Responsive 53

Characteristics:

Orphanet epidemiological data:

55
thiamine-responsive encephalopathy
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;
biotin-responsive basal ganglia disease
Inheritance: Autosomal recessive;

OMIM:

53
Inheritance:
autosomal recessive

Miscellaneous:
variable age at onset (birth to adolescence)
may be precipitated by minor illness (e.g., viral infection, fever)
responsive to high-dose biotin or biotin/thiamine treatment
dystonia and seizures may persist after resolution of episodes


HPO:

31
thiamine metabolism dysfunction syndrome 2:
Onset and clinical course juvenile onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Thiamine Metabolism Dysfunction Syndrome 2

OMIM : 53 Thiamine metabolism dysfunction syndrome-2 is an autosomal recessive metabolic disorder characterized by episodic encephalopathy, often triggered by febrile illness, presenting as confusion, seizures, external ophthalmoplegia, dysphagia, and sometimes coma and death. Administration of high doses of biotin, and sometimes thiamine, during these crises results in partial or complete improvement within days. If untreated, encephalopathies can result in permanent dystonia. Brain imaging may show characteristic bilateral lesions of the basal ganglia. It is not known why biotin administration results in clinical improvement, as the molecular basis of the disorder is mutation in a gene encoding a thiamine transporter. However, biotin may increase the gene expression of SLC19A3 (summary by Debs et al., 2010). For a discussion of genetic heterogeneity of disorders due to thiamine metabolism dysfunction, see THMD1 (249270). (607483)

MalaCards based summary : Thiamine Metabolism Dysfunction Syndrome 2, also known as biotin-responsive basal ganglia disease, is related to biotin-thiamine-responsive basal ganglia disease and beriberi, and has symptoms including fever, seizures and gait ataxia. An important gene associated with Thiamine Metabolism Dysfunction Syndrome 2 is SLC19A3 (Solute Carrier Family 19 Member 3), and among its related pathways/superpathways are Vitamin digestion and absorption and Metabolism. Affiliated tissues include brain, and related phenotypes are homeostasis/metabolism and digestive/alimentary

UniProtKB/Swiss-Prot : 71 Thiamine metabolism dysfunction syndrome 2, biotin- or thiamine-responsive type: An autosomal recessive metabolic disorder characterized by episodic encephalopathy, often triggered by febrile illness, presenting as confusion, seizures, external ophthalmoplegia, dysphagia, and sometimes coma and death. If untreated, encephalopathies can result in permanent dystonia. Brain imaging may show characteristic bilateral lesions of the basal ganglia.

Related Diseases for Thiamine Metabolism Dysfunction Syndrome 2

Graphical network of the top 20 diseases related to Thiamine Metabolism Dysfunction Syndrome 2:



Diseases related to Thiamine Metabolism Dysfunction Syndrome 2

Symptoms & Phenotypes for Thiamine Metabolism Dysfunction Syndrome 2

Symptoms via clinical synopsis from OMIM:

53
Neurologic Central Nervous System:
seizures
dystonia
gait ataxia
paraparesis
dysarthria
more
Abdomen Gastroin testinal:
dysphagia
swallowing difficulties

Head And Neck Eyes:
ptosis
nystagmus
external ophthalmoplegia
gaze palsy

Head And Neck Face:
facial dystonia


Clinical features from OMIM:

607483

Human phenotypes related to Thiamine Metabolism Dysfunction Syndrome 2:

31 (show all 22)
# Description HPO Frequency HPO Source Accession
1 fever 31 HP:0001945
2 seizures 31 HP:0001250
3 gait ataxia 31 HP:0002066
4 paraparesis 31 HP:0002385
5 ptosis 31 HP:0000508
6 nystagmus 31 HP:0000639
7 dysarthria 31 HP:0001260
8 dysphagia 31 HP:0002015
9 global developmental delay 31 occasional (7.5%) HP:0001263
10 irritability 31 HP:0000737
11 babinski sign 31 HP:0003487
12 inability to walk 31 HP:0002540
13 rigidity 31 HP:0002063
14 coma 31 HP:0001259
15 encephalopathy 31 HP:0001298
16 external ophthalmoplegia 31 HP:0000544
17 confusion 31 HP:0001289
18 mutism 31 HP:0002300
19 muscular hypotonia of the trunk 31 HP:0008936
20 abnormality of the basal ganglia 31 HP:0002134
21 craniofacial dystonia 31 HP:0012179
22 morphological abnormality of the pyramidal tract 31 HP:0002062

UMLS symptoms related to Thiamine Metabolism Dysfunction Syndrome 2:


gait ataxia, abnormal pyramidal signs, paraparesis, seizures, muscle rigidity

MGI Mouse Phenotypes related to Thiamine Metabolism Dysfunction Syndrome 2:

43
# Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 9.81 FOLR1 GCH1 SLC19A1 SLC19A2 SLC19A3 SLC25A19
2 digestive/alimentary MP:0005381 9.65 FOLR1 SLC19A1 SLC19A2 SLC19A3 SLC5A6
3 mortality/aging MP:0010768 9.56 FOLR1 GCH1 SLC19A1 SLC19A2 SLC19A3 SLC25A19
4 renal/urinary system MP:0005367 9.02 FOLR1 SLC19A1 SLC19A3 SLC25A19 SLC5A6

Drugs & Therapeutics for Thiamine Metabolism Dysfunction Syndrome 2

Search Clinical Trials , NIH Clinical Center for Thiamine Metabolism Dysfunction Syndrome 2

Genetic Tests for Thiamine Metabolism Dysfunction Syndrome 2

Genetic tests related to Thiamine Metabolism Dysfunction Syndrome 2:

# Genetic test Affiliating Genes
1 Basal Ganglia Disease, Biotin-Responsive 28 SLC19A3

Anatomical Context for Thiamine Metabolism Dysfunction Syndrome 2

MalaCards organs/tissues related to Thiamine Metabolism Dysfunction Syndrome 2:

38
Brain

Publications for Thiamine Metabolism Dysfunction Syndrome 2

Articles related to Thiamine Metabolism Dysfunction Syndrome 2:

(show all 16)
# Title Authors Year
1
Teaching NeuroImages: Biotin-responsive basal ganglia disease. ( 27164647 )
2016
2
Teaching NeuroImages: MRI findings of biotin-responsive basal ganglia disease before and after treatment. ( 26880816 )
2016
3
Depression in adult patients with biotin responsive basal ganglia disease. ( 27534451 )
2016
4
Biotin-responsive basal ganglia disease: a case diagnosed by whole exome sequencing. ( 25876998 )
2015
5
Treatment of biotin-responsive basal ganglia disease: Open comparative study between the combination of biotin plus thiamine versus thiamine alone. ( 26095097 )
2015
6
Biotin-Responsive Basal Ganglia Disease: Neuroimaging Features before and after Treatment. ( 24812013 )
2014
7
Biotin-responsive basal ganglia disease revisited: clinical, radiologic, and genetic findings. ( 23269594 )
2013
8
Biotin-Responsive Basal Ganglia Disease: A Treatable Differential Diagnosis of Leigh Syndrome. ( 24166474 )
2013
9
Biotin-responsive basal ganglia disease should be renamed biotin-thiamine-responsive basal ganglia disease: a retrospective review of the clinical, radiological and molecular findings of 18 new cases. ( 23742248 )
2013
10
Bilateral external ophthalmoplegia in biotin-responsive basal ganglia disease. ( 23360564 )
2013
11
Biotin-responsive basal ganglia disease in ethnic Europeans with novel SLC19A3 mutations. ( 20065143 )
2010
12
Biotin-responsive basal ganglia disease: a treatable and reversible neurological disorder of childhood. ( 19491117 )
2009
13
Biotin-responsive basal ganglia disease: case report and review of the literature. ( 19294600 )
2008
14
Biotin-responsive basal ganglia disease-linked mutations inhibit thiamine transport via hTHTR2: biotin is not a substrate for hTHTR2. ( 16790503 )
2006
15
Biotin-responsive basal ganglia disease maps to 2q36.3 and is due to mutations in SLC19A3. ( 15871139 )
2005
16
Biotin-responsive basal ganglia disease: a novel entity. ( 9679779 )
1998

Variations for Thiamine Metabolism Dysfunction Syndrome 2

UniProtKB/Swiss-Prot genetic disease variations for Thiamine Metabolism Dysfunction Syndrome 2:

71
# Symbol AA change Variation ID SNP ID
1 SLC19A3 p.Gly23Val VAR_025992 rs121917882
2 SLC19A3 p.Thr422Ala VAR_025993 rs121917884

ClinVar genetic disease variations for Thiamine Metabolism Dysfunction Syndrome 2:

6 (show all 11)
# Gene Variation Type Significance SNP ID Assembly Location
1 SLC19A3 NM_025243.3(SLC19A3): c.20C> A (p.Ser7Ter) single nucleotide variant Pathogenic rs713993048 GRCh37 Chromosome 2, 228567015: 228567015
2 SLC19A3 NM_025243.3(SLC19A3): c.74dupT (p.Ser26Leufs) duplication Pathogenic rs786205213 GRCh38 Chromosome 2, 227702245: 227702245
3 SLC19A3 NM_025243.3(SLC19A3): c.68G> T (p.Gly23Val) single nucleotide variant Pathogenic rs121917882 GRCh37 Chromosome 2, 228566967: 228566967
4 SLC19A3 NM_025243.3(SLC19A3): c.1264A> G (p.Thr422Ala) single nucleotide variant Pathogenic rs121917884 GRCh37 Chromosome 2, 228552932: 228552932
5 SLC19A3 SLC19A3, IVS3AS, A-G, -14 single nucleotide variant Pathogenic
6 SLC19A3 NM_025243.3(SLC19A3): c.130A> G (p.Lys44Glu) single nucleotide variant Pathogenic rs137852957 GRCh37 Chromosome 2, 228566905: 228566905
7 SLC19A3 NM_025243.3(SLC19A3): c.958G> C (p.Glu320Gln) single nucleotide variant Pathogenic rs137852958 GRCh37 Chromosome 2, 228563473: 228563473
8 SLC19A3 SLC19A3, 1-BP DUP, 74T duplication Pathogenic
9 SLC19A3 NM_025243.3(SLC19A3): c.337T> C (p.Tyr113His) single nucleotide variant Likely pathogenic rs145999922 GRCh37 Chromosome 2, 228564094: 228564094
10 SLC19A3 NM_025243.3(SLC19A3): c.81_82dupGA (p.Met28Argfs) duplication Pathogenic rs775835429 GRCh38 Chromosome 2, 227702237: 227702238
11 SLC19A3 NM_025243.3(SLC19A3): c.-4404_-3+408del deletion Pathogenic GRCh38 Chromosome 2, 227717535: 227722344

Expression for Thiamine Metabolism Dysfunction Syndrome 2

Search GEO for disease gene expression data for Thiamine Metabolism Dysfunction Syndrome 2.

Pathways for Thiamine Metabolism Dysfunction Syndrome 2

Pathways related to Thiamine Metabolism Dysfunction Syndrome 2 according to KEGG:

36
# Name Kegg Source Accession
1 Vitamin digestion and absorption hsa04977

Pathways related to Thiamine Metabolism Dysfunction Syndrome 2 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.6 FOLR2 GCH1 SLC19A1 SLC19A2 SLC19A3 SLC25A19
2
Show member pathways
12.11 FOLR2 SLC19A1 SLC19A2 SLC19A3 SLC25A19 SLC46A1
3
Show member pathways
11.96 FOLR1 FOLR2 SLC19A1 SLC46A1
4 10.95 FOLR1 FOLR2 SLC19A1 SLC46A1
5
Show member pathways
10.73 FOLR1 SLC19A1 SLC46A1
6 10.4 SLC19A1 SLC19A2 SLC19A3 SLC46A1 SLC5A6

GO Terms for Thiamine Metabolism Dysfunction Syndrome 2

Cellular components related to Thiamine Metabolism Dysfunction Syndrome 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 membrane GO:0016020 9.91 FOLR1 FOLR2 SLC19A1 SLC19A2 SLC19A3 SLC25A19
2 apical plasma membrane GO:0016324 9.33 FOLR1 SLC19A1 SLC46A1
3 anchored component of external side of plasma membrane GO:0031362 8.96 FOLR1 FOLR2
4 brush border membrane GO:0031526 8.8 FOLR1 SLC46A1 SLC5A6

Biological processes related to Thiamine Metabolism Dysfunction Syndrome 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 transport GO:0006810 9.97 FOLR1 FOLR2 SLC19A1 SLC19A2 SLC19A3 SLC25A19
2 vitamin transport GO:0051180 9.5 SLC19A1 SLC19A2 SLC19A3
3 thiamine transport GO:0015888 9.46 SLC19A2 SLC19A3
4 cellular response to folic acid GO:0071231 9.43 FOLR1 FOLR2
5 thiamine-containing compound metabolic process GO:0042723 9.43 SLC19A2 SLC19A3 SLC25A19
6 methotrexate transport GO:0051958 9.4 SLC19A1 SLC46A1
7 thiamine transmembrane transport GO:0071934 9.33 SLC19A2 SLC19A3 SLC25A19
8 folic acid metabolic process GO:0046655 9.26 FOLR1 FOLR2 SLC19A1 SLC46A1
9 folic acid transport GO:0015884 9.02 FOLR1 FOLR2 SLC19A1 SLC19A2 SLC46A1

Molecular functions related to Thiamine Metabolism Dysfunction Syndrome 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 drug binding GO:0008144 9.4 FOLR1 FOLR2
2 methotrexate binding GO:0051870 9.37 FOLR1 FOLR2
3 thiamine transmembrane transporter activity GO:0015234 9.33 SLC19A2 SLC19A3 SLC25A19
4 folic acid receptor activity GO:0061714 9.32 FOLR1 FOLR2
5 methotrexate transmembrane transporter activity GO:0015350 9.26 SLC19A1 SLC46A1
6 folic acid binding GO:0005542 9.26 FOLR1 FOLR2 SLC19A1 SLC46A1
7 folic acid transmembrane transporter activity GO:0008517 9.02 FOLR1 FOLR2 SLC19A1 SLC19A2 SLC46A1

Sources for Thiamine Metabolism Dysfunction Syndrome 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
Content
Loading form....