THMD4
MCID: THM014
MIFTS: 22

Thiamine Metabolism Dysfunction Syndrome 4 (THMD4)

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

Aliases & Classifications for Thiamine Metabolism Dysfunction Syndrome 4

MalaCards integrated aliases for Thiamine Metabolism Dysfunction Syndrome 4:

Name: Thiamine Metabolism Dysfunction Syndrome 4 57 13 73
Striatal Necrosis, Bilateral, and Progressive Polyneuropathy 57 29 6
Bilateral Striatal Degeneration and Progressive Polyneuropathy 57 75
Thmd4 57 75
Thiamine Metabolism Dysfunction Syndrome 4, Bilateral Striatal Degeneration and Progressive Polyneuropathy Type 75
Progressive Polyneuropathy with Bilateral Striatal Necrosis 59
Striatal Necrosis, Bilateral and Progressive Polyneuropathy 75
Thiamine Metabolism Dysfunction Syndrome, Type 4 40

Characteristics:

Orphanet epidemiological data:

59
progressive polyneuropathy with bilateral striatal necrosis
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
onset of acute encephalopathic attacks in childhood (3 to 7 years)
onset usually associated with febrile illness
full recovery after attacks
onset of chronic progressive polyneuropathy in late childhood
one family has been reported (as of january 2011)


HPO:

32
thiamine metabolism dysfunction syndrome 4:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Thiamine Metabolism Dysfunction Syndrome 4

OMIM : 57 Thiamine metabolism dysfunction syndrome-4 is an autosomal recessive metabolic disorder characterized by childhood onset of episodic encephalopathy, often associated with a febrile illness, and causing transient neurologic dysfunction. Most patients recover fully, but some may have mild residual weakness. Affected individuals also develop a slowly progressive axonal polyneuropathy beginning in childhood. Brain imaging during the acute episodes shows lesions consistent with bilateral striatal degeneration or necrosis (summary by Spiegel et al., 2009). For a discussion of genetic heterogeneity of disorders due to thiamine metabolism dysfunction, see THMD1 (249270). (613710)

MalaCards based summary : Thiamine Metabolism Dysfunction Syndrome 4, is also known as striatal necrosis, bilateral, and progressive polyneuropathy, and has symptoms including lethargy and weakness. An important gene associated with Thiamine Metabolism Dysfunction Syndrome 4 is SLC25A19 (Solute Carrier Family 25 Member 19). Affiliated tissues include brain and skeletal muscle, and related phenotypes are muscle weakness and skeletal muscle atrophy

UniProtKB/Swiss-Prot : 75 Thiamine metabolism dysfunction syndrome 4, bilateral striatal degeneration and progressive polyneuropathy type: A disease characterized by recurrent episodes of flaccid paralysis and encephalopathy associated with bilateral striatal necrosis and chronic progressive polyneuropathy.

Related Diseases for Thiamine Metabolism Dysfunction Syndrome 4

Diseases in the Thiamine Metabolism Dysfunction Syndrome 2 family:

Thiamine Metabolism Dysfunction Syndrome 4 Thiamine Metabolism Dysfunction Syndrome 5

Symptoms & Phenotypes for Thiamine Metabolism Dysfunction Syndrome 4

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
paralysis
lethargy
weakness
encephalopathic attacks, episodic, associated with infection
difficulty walking and running
more
Skeletal Feet:
foot deformities
pes equinus
forefoot adduction
forefoot supination

Muscle Soft Tissue:
distal muscle weakness due to neuropathy
distal muscle atrophy due to neuropathy

Neurologic Peripheral Nervous System:
hyporeflexia
axonal neuropathy
distal muscle weakness due to neuropathy (lower limbs more affected than upper limbs)
distal muscle atrophy due to neuropathy (lower limbs more affected than upper limbs)

Skeletal:
distal joint contractures, lower limbs

Laboratory Abnormalities:
increased csf lactate during acute episodes


Clinical features from OMIM:

613710

Human phenotypes related to Thiamine Metabolism Dysfunction Syndrome 4:

32 (show all 11)
# Description HPO Frequency HPO Source Accession
1 muscle weakness 32 HP:0001324
2 skeletal muscle atrophy 32 HP:0003202
3 talipes equinovarus 32 HP:0001762
4 paralysis 32 HP:0003470
5 difficulty walking 32 HP:0002355
6 hyporeflexia 32 HP:0001265
7 lethargy 32 HP:0001254
8 peripheral axonal neuropathy 32 HP:0003477
9 polyneuropathy 32 HP:0001271
10 increased csf lactate 32 HP:0002490
11 contractures of the joints of the lower limbs 32 HP:0005750

UMLS symptoms related to Thiamine Metabolism Dysfunction Syndrome 4:


lethargy, weakness

Drugs & Therapeutics for Thiamine Metabolism Dysfunction Syndrome 4

Search Clinical Trials , NIH Clinical Center for Thiamine Metabolism Dysfunction Syndrome 4

Genetic Tests for Thiamine Metabolism Dysfunction Syndrome 4

Genetic tests related to Thiamine Metabolism Dysfunction Syndrome 4:

# Genetic test Affiliating Genes
1 Striatal Necrosis, Bilateral, and Progressive Polyneuropathy 29 SLC25A19

Anatomical Context for Thiamine Metabolism Dysfunction Syndrome 4

MalaCards organs/tissues related to Thiamine Metabolism Dysfunction Syndrome 4:

41
Brain, Skeletal Muscle

Publications for Thiamine Metabolism Dysfunction Syndrome 4

Variations for Thiamine Metabolism Dysfunction Syndrome 4

UniProtKB/Swiss-Prot genetic disease variations for Thiamine Metabolism Dysfunction Syndrome 4:

75
# Symbol AA change Variation ID SNP ID
1 SLC25A19 p.Gly125Ser VAR_065125 rs387906944

ClinVar genetic disease variations for Thiamine Metabolism Dysfunction Syndrome 4:

6 (show all 12)
# Gene Variation Type Significance SNP ID Assembly Location
1 SLC25A19 NM_021734.4(SLC25A19): c.373G> A (p.Gly125Ser) single nucleotide variant Pathogenic rs387906944 GRCh37 Chromosome 17, 73279590: 73279590
2 SLC25A19 NM_021734.4(SLC25A19): c.373G> A (p.Gly125Ser) single nucleotide variant Pathogenic rs387906944 GRCh38 Chromosome 17, 75283509: 75283509
3 SLC25A19 NM_021734.4(SLC25A19): c.550G> C (p.Ala184Pro) single nucleotide variant Pathogenic rs769187207 GRCh38 Chromosome 17, 75278245: 75278245
4 SLC25A19 NM_021734.4(SLC25A19): c.550G> C (p.Ala184Pro) single nucleotide variant Pathogenic rs769187207 GRCh37 Chromosome 17, 73274326: 73274326
5 SLC25A19 NM_021734.4(SLC25A19): c.481G> A (p.Ala161Thr) single nucleotide variant Pathogenic GRCh37 Chromosome 17, 73274395: 73274395
6 SLC25A19 NM_021734.4(SLC25A19): c.481G> A (p.Ala161Thr) single nucleotide variant Pathogenic GRCh38 Chromosome 17, 75278314: 75278314
7 SLC25A19 NM_021734.4(SLC25A19): c.454C> A (p.Pro152Thr) single nucleotide variant Pathogenic GRCh37 Chromosome 17, 73279509: 73279509
8 SLC25A19 NM_021734.4(SLC25A19): c.454C> A (p.Pro152Thr) single nucleotide variant Pathogenic GRCh38 Chromosome 17, 75283428: 75283428
9 SLC25A19 NM_021734.4(SLC25A19): c.194C> T (p.Ala65Val) single nucleotide variant Pathogenic GRCh38 Chromosome 17, 75286398: 75286398
10 SLC25A19 NM_021734.4(SLC25A19): c.194C> T (p.Ala65Val) single nucleotide variant Pathogenic GRCh37 Chromosome 17, 73282479: 73282479
11 SLC25A19 NM_021734.4(SLC25A19): c.240A> C (p.Lys80Asn) single nucleotide variant Likely pathogenic GRCh37 Chromosome 17, 73282433: 73282433
12 SLC25A19 NM_021734.4(SLC25A19): c.240A> C (p.Lys80Asn) single nucleotide variant Likely pathogenic GRCh38 Chromosome 17, 75286352: 75286352

Expression for Thiamine Metabolism Dysfunction Syndrome 4

Search GEO for disease gene expression data for Thiamine Metabolism Dysfunction Syndrome 4.

Pathways for Thiamine Metabolism Dysfunction Syndrome 4

GO Terms for Thiamine Metabolism Dysfunction Syndrome 4

Sources for Thiamine Metabolism Dysfunction Syndrome 4

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 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 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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