THMD5
MCID: THM013
MIFTS: 23

Thiamine Metabolism Dysfunction Syndrome 5 (THMD5)

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

Aliases & Classifications for Thiamine Metabolism Dysfunction Syndrome 5

MalaCards integrated aliases for Thiamine Metabolism Dysfunction Syndrome 5:

Name: Thiamine Metabolism Dysfunction Syndrome 5 57 29 13 6 73
Thmd5 57 75
Thiamine Metabolism Dysfunction Syndrome 5, Episodic Encephalopathy Type 75
Encephalopathy, Episodic, Due to Thiamine Pyrophosphokinase Deficiency 57
Childhood Encephalopathy Due to Thiamine Pyrophosphokinase Deficiency 59
Episodic Encephalopathy Due to Thiamine Pyrophosphokinase Deficiency 75

Characteristics:

Orphanet epidemiological data:

59
childhood encephalopathy due to thiamine pyrophosphokinase deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
highly variable phenotype
onset in early childhood
some features may be progressive
encephalopathic episodes associated with increased serum and csf lactate
thiamine supplementation may be beneficial


HPO:

32
thiamine metabolism dysfunction syndrome 5:
Onset and clinical course phenotypic variability
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 59  
Inborn errors of metabolism


Summaries for Thiamine Metabolism Dysfunction Syndrome 5

OMIM : 57 Episodic encephalopathy due to thiamine pyrophosphokinase deficiency is an autosomal recessive metabolic disorder due to an inborn error of thiamine metabolism. The phenotype is highly variable, but in general, affected individuals have onset in early childhood of acute encephalopathic episodes associated with increased serum and CSF lactate. These episodes result in progressive neurologic dysfunction manifest as gait disturbances, ataxia, dystonia, and spasticity, which in some cases may result in loss of ability to walk. Cognitive function is usually preserved, although mildly delayed development has been reported. These episodes are usually associated with infection and metabolic decompensation. Some patients may have recovery of some neurologic deficits (summary by Mayr et al., 2011). For a discussion of genetic heterogeneity of disorders due to thiamine metabolism dysfunction, see THMD1 (249270). (614458)

MalaCards based summary : Thiamine Metabolism Dysfunction Syndrome 5, also known as thmd5, is related to childhood encephalopathy due to thiamine pyrophosphokinase deficiency, and has symptoms including ataxia and muscle spasticity. An important gene associated with Thiamine Metabolism Dysfunction Syndrome 5 is TPK1 (Thiamin Pyrophosphokinase 1). Affiliated tissues include brain and cerebellum, and related phenotypes are seizures and ataxia

UniProtKB/Swiss-Prot : 75 Thiamine metabolism dysfunction syndrome 5, episodic encephalopathy type: An autosomal recessive metabolic disorder due to an inborn error of thiamine metabolism. The phenotype is highly variable, but in general, affected individuals have onset in early childhood of acute encephalopathic episodes associated with increased serum and CSF lactate. These episodes result in progressive neurologic dysfunction manifest as gait disturbances, ataxia, dystonia, and spasticity, which in some cases may result in loss of ability to walk. Cognitive function is usually preserved, although mildly delayed development has been reported. These episodes are usually associated with infection and metabolic decompensation. Some patients may have recovery of some neurologic deficits.

Related Diseases for Thiamine Metabolism Dysfunction Syndrome 5

Diseases in the Thiamine Metabolism Dysfunction Syndrome 2 family:

Thiamine Metabolism Dysfunction Syndrome 4 Thiamine Metabolism Dysfunction Syndrome 5

Diseases related to Thiamine Metabolism Dysfunction Syndrome 5 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 childhood encephalopathy due to thiamine pyrophosphokinase deficiency 11.1

Symptoms & Phenotypes for Thiamine Metabolism Dysfunction Syndrome 5

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
ataxia
spasticity
dystonia
hypotonia
normal cognition
more
Metabolic Features:
metabolic crises
lactic acidosis, episodic

Laboratory Abnormalities:
increased urinary alpha-ketoglutaric acid, intermittent
decreased serum thiamine pyrophosphate

Muscle Soft Tissue:
hypotonia
pyruvate oxidation defect
decreased thiamine pyrophosphate

Cardiovascular Heart:
left ventricular hypertrophy (1 patient)


Clinical features from OMIM:

614458

Human phenotypes related to Thiamine Metabolism Dysfunction Syndrome 5:

32 (show all 10)
# Description HPO Frequency HPO Source Accession
1 seizures 32 occasional (7.5%) HP:0001250
2 ataxia 32 HP:0001251
3 spasticity 32 HP:0001257
4 global developmental delay 32 occasional (7.5%) HP:0001263
5 dystonia 32 HP:0001332
6 lactic acidosis 32 HP:0003128
7 left ventricular hypertrophy 32 occasional (7.5%) HP:0001712
8 vertigo 32 HP:0002321
9 generalized hypotonia 32 HP:0001290
10 loss of speech 32 occasional (7.5%) HP:0002371

UMLS symptoms related to Thiamine Metabolism Dysfunction Syndrome 5:


ataxia, muscle spasticity

Drugs & Therapeutics for Thiamine Metabolism Dysfunction Syndrome 5

Search Clinical Trials , NIH Clinical Center for Thiamine Metabolism Dysfunction Syndrome 5

Genetic Tests for Thiamine Metabolism Dysfunction Syndrome 5

Genetic tests related to Thiamine Metabolism Dysfunction Syndrome 5:

# Genetic test Affiliating Genes
1 Thiamine Metabolism Dysfunction Syndrome 5 (episodic Encephalopathy Type) 29 TPK1

Anatomical Context for Thiamine Metabolism Dysfunction Syndrome 5

MalaCards organs/tissues related to Thiamine Metabolism Dysfunction Syndrome 5:

41
Brain, Cerebellum

Publications for Thiamine Metabolism Dysfunction Syndrome 5

Variations for Thiamine Metabolism Dysfunction Syndrome 5

UniProtKB/Swiss-Prot genetic disease variations for Thiamine Metabolism Dysfunction Syndrome 5:

75
# Symbol AA change Variation ID SNP ID
1 TPK1 p.Leu40Pro VAR_067391 rs387906936
2 TPK1 p.Asn50His VAR_067392 rs387906935
3 TPK1 p.Asn219Ser VAR_067393 rs371271054

ClinVar genetic disease variations for Thiamine Metabolism Dysfunction Syndrome 5:

6 (show all 40)
# Gene Variation Type Significance SNP ID Assembly Location
1 TPK1 NM_022445.3(TPK1): c.148A> C (p.Asn50His) single nucleotide variant Pathogenic rs387906935 GRCh37 Chromosome 7, 144380039: 144380039
2 TPK1 NM_022445.3(TPK1): c.148A> C (p.Asn50His) single nucleotide variant Pathogenic rs387906935 GRCh38 Chromosome 7, 144682946: 144682946
3 TPK1 TPK1, IVS7DS, A-T, +4 single nucleotide variant Pathogenic
4 TPK1 NM_022445.3(TPK1): c.119T> C (p.Leu40Pro) single nucleotide variant Uncertain significance rs387906936 GRCh37 Chromosome 7, 144380068: 144380068
5 TPK1 NM_022445.3(TPK1): c.119T> C (p.Leu40Pro) single nucleotide variant Uncertain significance rs387906936 GRCh38 Chromosome 7, 144682975: 144682975
6 TPK1 TPK1, 4-BP DEL, 179GAGA deletion Pathogenic
7 TPK1 NM_022445.3(TPK1): c.656A> G (p.Asn219Ser) single nucleotide variant Pathogenic rs371271054 GRCh37 Chromosome 7, 144150714: 144150714
8 TPK1 NM_022445.3(TPK1): c.656A> G (p.Asn219Ser) single nucleotide variant Pathogenic rs371271054 GRCh38 Chromosome 7, 144453621: 144453621
9 TPK1 NM_022445.3(TPK1): c.663C> T (p.Tyr221=) single nucleotide variant Benign rs113536847 GRCh37 Chromosome 7, 144150707: 144150707
10 TPK1 NM_022445.3(TPK1): c.663C> T (p.Tyr221=) single nucleotide variant Benign rs113536847 GRCh38 Chromosome 7, 144453614: 144453614
11 TPK1 NM_022445.3(TPK1): c.98G> A (p.Arg33His) single nucleotide variant Benign/Likely benign rs77358162 GRCh37 Chromosome 7, 144462990: 144462990
12 TPK1 NM_022445.3(TPK1): c.98G> A (p.Arg33His) single nucleotide variant Benign/Likely benign rs77358162 GRCh38 Chromosome 7, 144765897: 144765897
13 TPK1 NM_022445.3(TPK1): c.501+4A> T single nucleotide variant Pathogenic rs375169579 GRCh38 Chromosome 7, 144591419: 144591419
14 TPK1 NM_022445.3(TPK1): c.501+4A> T single nucleotide variant Pathogenic rs375169579 GRCh37 Chromosome 7, 144288512: 144288512
15 TPK1 NM_022445.3(TPK1): c.366C> T (p.Ile122=) single nucleotide variant Benign/Likely benign rs863224236 GRCh38 Chromosome 7, 144591558: 144591558
16 TPK1 NM_022445.3(TPK1): c.366C> T (p.Ile122=) single nucleotide variant Benign/Likely benign rs863224236 GRCh37 Chromosome 7, 144288651: 144288651
17 TPK1 NM_022445.3(TPK1): c.614-1G> A single nucleotide variant Pathogenic rs776874412 GRCh37 Chromosome 7, 144150757: 144150757
18 TPK1 NM_022445.3(TPK1): c.614-1G> A single nucleotide variant Pathogenic rs776874412 GRCh38 Chromosome 7, 144453664: 144453664
19 TPK1 NM_022445.3(TPK1): c.395T> C (p.Phe132Ser) single nucleotide variant Pathogenic GRCh37 Chromosome 7, 144288622: 144288622
20 TPK1 NM_022445.3(TPK1): c.395T> C (p.Phe132Ser) single nucleotide variant Pathogenic GRCh38 Chromosome 7, 144591529: 144591529
21 TPK1 NM_022445.3(TPK1): c.154T> C (p.Leu52=) single nucleotide variant Likely benign rs759534507 GRCh38 Chromosome 7, 144682940: 144682940
22 TPK1 NM_022445.3(TPK1): c.154T> C (p.Leu52=) single nucleotide variant Likely benign rs759534507 GRCh37 Chromosome 7, 144380033: 144380033
23 TPK1 NM_022445.3(TPK1): c.677T> A (p.Val226Asp) single nucleotide variant Uncertain significance rs550639617 GRCh37 Chromosome 7, 144150693: 144150693
24 TPK1 NM_022445.3(TPK1): c.677T> A (p.Val226Asp) single nucleotide variant Uncertain significance rs550639617 GRCh38 Chromosome 7, 144453600: 144453600
25 TPK1 NM_022445.3(TPK1): c.576T> G (p.Cys192Trp) single nucleotide variant Likely pathogenic GRCh37 Chromosome 7, 144245621: 144245621
26 TPK1 NM_022445.3(TPK1): c.576T> G (p.Cys192Trp) single nucleotide variant Likely pathogenic GRCh38 Chromosome 7, 144548528: 144548528
27 TPK1 NM_022445.3(TPK1): c.489C> T (p.Tyr163=) single nucleotide variant Likely benign GRCh37 Chromosome 7, 144288528: 144288528
28 TPK1 NM_022445.3(TPK1): c.489C> T (p.Tyr163=) single nucleotide variant Likely benign GRCh38 Chromosome 7, 144591435: 144591435
29 TPK1 NM_022445.3(TPK1): c.151C> T (p.Arg51Cys) single nucleotide variant Uncertain significance rs761924102 GRCh38 Chromosome 7, 144682943: 144682943
30 TPK1 NM_022445.3(TPK1): c.151C> T (p.Arg51Cys) single nucleotide variant Uncertain significance rs761924102 GRCh37 Chromosome 7, 144380036: 144380036
31 TPK1 NM_022445.3(TPK1): c.425T> C (p.Leu142Ser) single nucleotide variant Uncertain significance GRCh37 Chromosome 7, 144288592: 144288592
32 TPK1 NM_022445.3(TPK1): c.425T> C (p.Leu142Ser) single nucleotide variant Uncertain significance GRCh38 Chromosome 7, 144591499: 144591499
33 TPK1 NM_022445.3(TPK1): c.174A> T (p.Gly58=) single nucleotide variant Uncertain significance rs1049396049 GRCh37 Chromosome 7, 144380013: 144380013
34 TPK1 NM_022445.3(TPK1): c.174A> T (p.Gly58=) single nucleotide variant Uncertain significance rs1049396049 GRCh38 Chromosome 7, 144682920: 144682920
35 TPK1 NM_022445.3(TPK1): c.559C> T (p.Pro187Ser) single nucleotide variant Uncertain significance GRCh38 Chromosome 7, 144548545: 144548545
36 TPK1 NM_022445.3(TPK1): c.559C> T (p.Pro187Ser) single nucleotide variant Uncertain significance GRCh37 Chromosome 7, 144245638: 144245638
37 TPK1 NM_022445.3(TPK1): c.337G> A (p.Glu113Lys) single nucleotide variant Uncertain significance GRCh38 Chromosome 7, 144623183: 144623183
38 TPK1 NM_022445.3(TPK1): c.337G> A (p.Glu113Lys) single nucleotide variant Uncertain significance GRCh37 Chromosome 7, 144320276: 144320276
39 TPK1 NC_000007.14: g.(?_144623146)_(144682998_?)del deletion Uncertain significance GRCh37 Chromosome 7, 144320239: 144380091
40 TPK1 NC_000007.14: g.(?_144623146)_(144682998_?)del deletion Uncertain significance GRCh38 Chromosome 7, 144623146: 144682998

Expression for Thiamine Metabolism Dysfunction Syndrome 5

Search GEO for disease gene expression data for Thiamine Metabolism Dysfunction Syndrome 5.

Pathways for Thiamine Metabolism Dysfunction Syndrome 5

GO Terms for Thiamine Metabolism Dysfunction Syndrome 5

Sources for Thiamine Metabolism Dysfunction Syndrome 5

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
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30 HGMD
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32 HPO
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44 MeSH
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58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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