THMD5
MCID: THM013
MIFTS: 32

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 70
Thmd5 57 20 72
Childhood Encephalopathy Due to Thiamine Pyrophosphokinase Deficiency 20 58
Episodic Encephalopathy Due to Thiamine Pyrophosphokinase Deficiency 20 72
Thiamine Pyrophosphokinase Deficiency 20 36
Thiamine Metabolism Dysfunction Syndrome 5, Episodic Encephalopathy Type 72
Encephalopathy, Episodic, Due to Thiamine Pyrophosphokinase Deficiency 57
Thiamine Metabolism Dysfunction Syndrome, Type 5 39
Thiamine Metabolism Dysfunction Syndrome-5 20

Characteristics:

Orphanet epidemiological data:

58
childhood encephalopathy due to thiamine pyrophosphokinase deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM®:

57 (Updated 20-May-2021)
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:

31
thiamine metabolism dysfunction syndrome 5:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Inborn errors of metabolism


External Ids:

OMIM® 57 614458
OMIM Phenotypic Series 57 PS249270
KEGG 36 H01567
MeSH 44 D020739
ICD10 via Orphanet 33 G96.8
Orphanet 58 ORPHA293955
MedGen 41 C3280866
UMLS 70 C3280866

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) (Updated 20-May-2021)

MalaCards based summary : Thiamine Metabolism Dysfunction Syndrome 5, also known as thmd5, is related to encephalopathy and ataxia and polyneuropathy, adult-onset, and has symptoms including ataxia and muscle spasticity. An important gene associated with Thiamine Metabolism Dysfunction Syndrome 5 is TPK1 (Thiamin Pyrophosphokinase 1), and among its related pathways/superpathways is Thiamine metabolism. Affiliated tissues include cerebellum and brain, and related phenotypes are global developmental delay and left ventricular hypertrophy

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 293955 Definition Childhood encephalopathy due to thiamine pyrophosphokinase deficiency is a rare inborn error of metabolism disorder characterized by early-onset, acute, encephalopathic episodes (frequently triggered by viral infections), associated with lactic acidosis and alpha-ketoglutaric aciduria, which typically manifest with variable degrees of ataxia, generalized developmental regression (which deteriorates with each episode) and dystonia. Other manifestations include spasticity, seizures, truncal hypotonia, limb hypertonia, brisk tendon reflexes and reversible coma.

KEGG : 36 Thiamine pyrophosphokinase (TPK) deficiency is a recently described rare disorder that present as episodic encephalopathy or Leigh syndrome like early-onset global developmental delay. TPK deficiency is one of thiamine metabolism dysfunction syndrome caused by mutations TPK1. TPK produces thiamine pyrophosphate (TPP). TPP is a cofactor for enzymes important in a range of fundamental processes such as cellular respiration. It has been reported that early thiamine supplementation prevented encephalopathic episodes and improved developmental progression.

UniProtKB/Swiss-Prot : 72 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 encephalopathy 10.4
2 ataxia and polyneuropathy, adult-onset 10.4
3 leigh syndrome 10.3
4 lactic acidosis 10.3
5 dystonia 10.3
6 hypotonia 10.3
7 branchiootic syndrome 1 10.1
8 movement disease 10.1
9 mitochondrial dna-associated leigh syndrome and narp 10.1
10 nuclear gene-encoded leigh syndrome spectrum 10.1

Graphical network of the top 20 diseases related to Thiamine Metabolism Dysfunction Syndrome 5:



Diseases related to Thiamine Metabolism Dysfunction Syndrome 5

Symptoms & Phenotypes for Thiamine Metabolism Dysfunction Syndrome 5

Human phenotypes related to Thiamine Metabolism Dysfunction Syndrome 5:

31 (show all 10)
# Description HPO Frequency HPO Source Accession
1 global developmental delay 31 occasional (7.5%) HP:0001263
2 left ventricular hypertrophy 31 occasional (7.5%) HP:0001712
3 loss of speech 31 occasional (7.5%) HP:0002371
4 seizure 31 occasional (7.5%) HP:0001250
5 spasticity 31 HP:0001257
6 ataxia 31 HP:0001251
7 vertigo 31 HP:0002321
8 dystonia 31 HP:0001332
9 lactic acidosis 31 HP:0003128
10 generalized hypotonia 31 HP:0001290

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Neurologic Central Nervous System:
spasticity
ataxia
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 (Updated 20-May-2021)

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:

40
Cerebellum, Brain

Publications for Thiamine Metabolism Dysfunction Syndrome 5

Articles related to Thiamine Metabolism Dysfunction Syndrome 5:

# Title Authors PMID Year
1
Thiamine pyrophosphokinase deficiency in encephalopathic children with defects in the pyruvate oxidation pathway. 6 57
22152682 2011
2
Expanding the clinical and molecular spectrum of thiamine pyrophosphokinase deficiency: a treatable neurological disorder caused by TPK1 mutations. 6
25458521 2014
3
Thiamine Pyrophosphokinase Deficiency due to Mutations in the TPK1 Gene: A Rare, Treatable Neurodegenerative Disorder. 61
33231275 2021
4
Eleven novel mutations and clinical characteristics in seven Chinese patients with thiamine metabolism dysfunction syndrome. 61
32679198 2020
5
Whole Exome Sequencing Identifies a Novel Mutation of TPK1 in a Chinese Family with Recurrent Ataxia. 61
32361878 2020
6
Identification of two novel TPK1 gene mutations in a Chinese patient with thiamine pyrophosphokinase deficiency undergoing whole exome sequencing. 61
30789823 2019

Variations for Thiamine Metabolism Dysfunction Syndrome 5

ClinVar genetic disease variations for Thiamine Metabolism Dysfunction Syndrome 5:

6 (show top 50) (show all 93)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 TPK1 NM_022445.4(TPK1):c.148A>C (p.Asn50His) SNV Pathogenic 30568 rs387906935 GRCh37: 7:144380039-144380039
GRCh38: 7:144682946-144682946
2 TPK1 TPK1, IVS7DS, A-T, +4 SNV Pathogenic 30569 GRCh37:
GRCh38:
3 TPK1 TPK1, 4-BP DEL, 179GAGA Deletion Pathogenic 30571 GRCh37:
GRCh38:
4 TPK1 NM_022445.4(TPK1):c.395T>C (p.Phe132Ser) SNV Pathogenic 438734 rs1417315589 GRCh37: 7:144288622-144288622
GRCh38: 7:144591529-144591529
5 TPK1 NM_022445.4(TPK1):c.614-1G>A SNV Pathogenic 438735 rs776874412 GRCh37: 7:144150757-144150757
GRCh38: 7:144453664-144453664
6 TPK1 NC_000007.14:g.(?_144682889)_(144765971_?)del Deletion Pathogenic 832084 GRCh37: 7:144379982-144463064
GRCh38:
7 TPK1 NC_000007.14:g.(?_144591403)_(144835622_?)del Deletion Pathogenic 833116 GRCh37: 7:144288496-144532715
GRCh38:
8 TPK1 NM_022445.4(TPK1):c.405del (p.Met136fs) Deletion Pathogenic 944675 GRCh37: 7:144288612-144288612
GRCh38: 7:144591519-144591519
9 TPK1 NM_022445.4(TPK1):c.119T>C (p.Leu40Pro) SNV Pathogenic 30570 rs387906936 GRCh37: 7:144380068-144380068
GRCh38: 7:144682975-144682975
10 TPK1 NC_000007.14:g.(?_144682889)_(144682998_?)del Deletion Pathogenic 665627 GRCh37: 7:144379982-144380091
GRCh38: 7:144682889-144682998
11 TPK1 NM_022445.4(TPK1):c.656A>G (p.Asn219Ser) SNV Pathogenic 30572 rs371271054 GRCh37: 7:144150714-144150714
GRCh38: 7:144453621-144453621
12 TPK1 NM_022445.4(TPK1):c.664G>C (p.Asp222His) SNV Pathogenic 419232 rs368458768 GRCh37: 7:144150706-144150706
GRCh38: 7:144453613-144453613
13 TPK1 NM_022445.4(TPK1):c.246C>A (p.Tyr82Ter) SNV Pathogenic 962978 GRCh37: 7:144345912-144345912
GRCh38: 7:144648819-144648819
14 TPK1 NM_022445.4(TPK1):c.501+4A>T SNV Pathogenic/Likely pathogenic 215275 rs375169579 GRCh37: 7:144288512-144288512
GRCh38: 7:144591419-144591419
15 TPK1 NM_022445.4(TPK1):c.44-2A>G SNV Likely pathogenic 215276 rs863224237 GRCh37: 7:144463046-144463046
GRCh38: 7:144765953-144765953
16 TPK1 NM_022445.4(TPK1):c.576T>G (p.Cys192Trp) SNV Likely pathogenic 488625 rs1554523224 GRCh37: 7:144245621-144245621
GRCh38: 7:144548528-144548528
17 TPK1 NM_022445.4(TPK1):c.19C>T (p.Pro7Ser) SNV Likely pathogenic 972916 GRCh37: 7:144532677-144532677
GRCh38: 7:144835584-144835584
18 TPK1 NM_022445.4(TPK1):c.382C>T (p.Leu128Phe) SNV Likely pathogenic 972917 GRCh37: 7:144288635-144288635
GRCh38: 7:144591542-144591542
19 TPK1 NM_022445.4(TPK1):c.426G>C (p.Leu142Phe) SNV Conflicting interpretations of pathogenicity 265278 rs769525399 GRCh37: 7:144288591-144288591
GRCh38: 7:144591498-144591498
20 TPK1 NM_022445.4(TPK1):c.512G>C (p.Arg171Thr) SNV Uncertain significance 1035404 GRCh37: 7:144245685-144245685
GRCh38: 7:144548592-144548592
21 TPK1 NC_000007.13:g.(?_144245564)_(144245715_?)del Deletion Uncertain significance 1036661 GRCh37: 7:144245564-144245715
GRCh38:
22 TPK1 NM_022445.4(TPK1):c.160_162del (p.Asp54del) Deletion Uncertain significance 1038125 GRCh37: 7:144380025-144380027
GRCh38: 7:144682932-144682934
23 TPK1 NM_022445.4(TPK1):c.56A>G (p.Tyr19Cys) SNV Uncertain significance 1041153 GRCh37: 7:144463032-144463032
GRCh38: 7:144765939-144765939
24 TPK1 NM_022445.4(TPK1):c.22T>A (p.Leu8Met) SNV Uncertain significance 1043898 GRCh37: 7:144532674-144532674
GRCh38: 7:144835581-144835581
25 TPK1 NM_022445.4(TPK1):c.127G>A (p.Ala43Thr) SNV Uncertain significance 651042 rs756505847 GRCh37: 7:144380060-144380060
GRCh38: 7:144682967-144682967
26 TPK1 NM_022445.4(TPK1):c.687G>A (p.Val229=) SNV Uncertain significance 855208 GRCh37: 7:144150683-144150683
GRCh38: 7:144453590-144453590
27 TPK1 NM_022445.4(TPK1):c.482T>A (p.Leu161Gln) SNV Uncertain significance 942673 GRCh37: 7:144288535-144288535
GRCh38: 7:144591442-144591442
28 TPK1 NM_022445.4(TPK1):c.620A>T (p.Asp207Val) SNV Uncertain significance 1048796 GRCh37: 7:144150750-144150750
GRCh38: 7:144453657-144453657
29 TPK1 NM_022445.4(TPK1):c.43+6G>T SNV Uncertain significance 1056560 GRCh37: 7:144532647-144532647
GRCh38: 7:144835554-144835554
30 TPK1 NM_022445.4(TPK1):c.546G>C (p.Trp182Cys) SNV Uncertain significance 1064004 GRCh37: 7:144245651-144245651
GRCh38: 7:144548558-144548558
31 TPK1 NC_000007.14:g.(?_144623146)_(144682998_?)del Deletion Uncertain significance 583968 GRCh37: 7:144320239-144380091
GRCh38: 7:144623146-144682998
32 TPK1 NC_000007.14:g.(?_144591403)_(144591589_?)del Deletion Uncertain significance 650708 GRCh37: 7:144288496-144288682
GRCh38: 7:144591403-144591589
33 TPK1 NC_000007.14:g.(?_144765860)_(144765971_?)del Deletion Uncertain significance 832194 GRCh37: 7:144462953-144463064
GRCh38:
34 TPK1 NC_000007.14:g.(?_144453525)_(144548622_?)dup Duplication Uncertain significance 832487 GRCh37: 7:144150618-144245715
GRCh38:
35 TPK1 NM_022445.4(TPK1):c.667G>A (p.Gly223Arg) SNV Uncertain significance 1000048 GRCh37: 7:144150703-144150703
GRCh38: 7:144453610-144453610
36 TPK1 NM_022445.4(TPK1):c.92A>G (p.Tyr31Cys) SNV Uncertain significance 1005577 GRCh37: 7:144462996-144462996
GRCh38: 7:144765903-144765903
37 TPK1 NM_022445.4(TPK1):c.53A>G (p.Lys18Arg) SNV Uncertain significance 1006341 GRCh37: 7:144463035-144463035
GRCh38: 7:144765942-144765942
38 TPK1 NM_022445.4(TPK1):c.206A>G (p.Asn69Ser) SNV Uncertain significance 1009588 GRCh37: 7:144345952-144345952
GRCh38: 7:144648859-144648859
39 TPK1 NM_022445.4(TPK1):c.704T>C (p.Leu235Pro) SNV Uncertain significance 1010608 GRCh37: 7:144150666-144150666
GRCh38: 7:144453573-144453573
40 TPK1 NM_022445.4(TPK1):c.662ACG[3] (p.Asp222dup) Microsatellite Uncertain significance 1011909 GRCh37: 7:144150702-144150703
GRCh38: 7:144453609-144453610
41 TPK1 NM_022445.4(TPK1):c.425T>C (p.Leu142Ser) SNV Uncertain significance 540078 rs1265314976 GRCh37: 7:144288592-144288592
GRCh38: 7:144591499-144591499
42 TPK1 NM_022445.4(TPK1):c.355-4T>G SNV Uncertain significance 389409 rs568693004 GRCh37: 7:144288666-144288666
GRCh38: 7:144591573-144591573
43 TPK1 NM_022445.4(TPK1):c.371C>T (p.Thr124Ile) SNV Uncertain significance 663896 rs754068899 GRCh37: 7:144288646-144288646
GRCh38: 7:144591553-144591553
44 TPK1 NM_022445.4(TPK1):c.700C>T (p.Pro234Ser) SNV Uncertain significance 838985 GRCh37: 7:144150670-144150670
GRCh38: 7:144453577-144453577
45 TPK1 NM_022445.4(TPK1):c.230C>T (p.Pro77Leu) SNV Uncertain significance 850686 GRCh37: 7:144345928-144345928
GRCh38: 7:144648835-144648835
46 TPK1 NM_022445.4(TPK1):c.239G>A (p.Arg80Lys) SNV Uncertain significance 942133 GRCh37: 7:144345919-144345919
GRCh38: 7:144648826-144648826
47 TPK1 NM_022445.4(TPK1):c.535G>C (p.Glu179Gln) SNV Uncertain significance 942296 GRCh37: 7:144245662-144245662
GRCh38: 7:144548569-144548569
48 TPK1 NM_022445.4(TPK1):c.442A>G (p.Ile148Val) SNV Uncertain significance 1017192 GRCh37: 7:144288575-144288575
GRCh38: 7:144591482-144591482
49 TPK1 NM_022445.4(TPK1):c.305C>G (p.Thr102Ser) SNV Uncertain significance 1022000 GRCh37: 7:144320308-144320308
GRCh38: 7:144623215-144623215
50 TPK1 NM_022445.4(TPK1):c.44-3T>C SNV Uncertain significance 1023554 GRCh37: 7:144463047-144463047
GRCh38: 7:144765954-144765954

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

72
# 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

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

Pathways related to Thiamine Metabolism Dysfunction Syndrome 5 according to KEGG:

36
# Name Kegg Source Accession
1 Thiamine metabolism hsa00730

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 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 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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