TPID
MCID: TRS021
MIFTS: 38

Triosephosphate Isomerase Deficiency (TPID)

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

Aliases & Classifications for Triosephosphate Isomerase Deficiency

MalaCards integrated aliases for Triosephosphate Isomerase Deficiency:

Name: Triosephosphate Isomerase Deficiency 58 12 77 54 26 76 30 6 15 41 74
Triose Phosphate-Isomerase Deficiency 12 54 60
Tpid 58 26 76
Hemolytic Anemia Due to Triosephosphate Isomerase Deficiency 58 76
Triose Phosphate Isomerase Deficiency 26 74
Tpi Deficiency 54 26
Hereditary Nonspherocytic Hemolytic Anemia Due to Triosephosphate Isomerase Deficiency 26
Deficiency of Phosphotriose Isomerase 26

Characteristics:

Orphanet epidemiological data:

60
triose phosphate-isomerase deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Neonatal;

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
onset of hemolytic anemia shortly after birth
onset of neuromuscular symptoms between 6 months and 1 year of age
death in childhood due to respiratory failure may occur


HPO:

33
triosephosphate isomerase deficiency:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Triosephosphate Isomerase Deficiency

NIH Rare Diseases : 54 Triosephosphate isomerase (TPI) deficiency is a severe disorder characterized by a shortage of red blood cells (hemolytic anemia), neurological problems, infections, and muscle weakness that can affect breathing and heart function. TPI deficiency is the most severe form of a group of diseases known as glycolytic enzymopathies, which are rare genetic diseases that lead to the degeneration of the red blood cells.  Signs and symptoms include anemia, fatigue, pallor, yellowing of the skin and the white of the eyes (jaundice), and shortness of breath. Other symptoms are muscle weakness and wasting (atrophy), movement problems (such as involuntary muscle contractions (dystonia), tremors and weak muscle tone), seizures, cardiomyopathy, and diaphragm weakness which may cause breathing problems and lead to respiratory failure. The disease is caused by mutations in the TPI1 gene. Inheritance is autosomal recessive. Treatment is directed toward the specific symptoms that are present in each person. 

MalaCards based summary : Triosephosphate Isomerase Deficiency, also known as triose phosphate-isomerase deficiency, is related to hemolytic anemia and myopathy, and has symptoms including tremor, abnormal pyramidal signs and icterus. An important gene associated with Triosephosphate Isomerase Deficiency is TPI1 (Triosephosphate Isomerase 1). Affiliated tissues include skin, eye and skeletal muscle, and related phenotypes are muscular hypotonia and skeletal muscle atrophy

Disease Ontology : 12 A glucose metabolism disorder that is characterized by chronic haemolytic anaemia, cardiomyopathy, susceptibility to infections and severe neurological dysfunction, and has material basis in the triosephosphate isomerase enzyme (TPI1) gene inherited as an autosomal recessive trait.

Genetics Home Reference : 26 Triosephosphate isomerase deficiency is a disorder characterized by a shortage of red blood cells (anemia), movement problems, increased susceptibility to infection, and muscle weakness that can affect breathing and heart function.

OMIM : 58 Triosephosphate isomerase deficiency is an autosomal recessive multisystem disorder characterized by congenital hemolytic anemia, and progressive neuromuscular dysfunction beginning in early childhood. Many patients die from respiratory failure in childhood. The neurologic syndrome is variable, but usually includes lower motor neuron dysfunction with hypotonia, muscle weakness and atrophy, and hyporeflexia. Some patients may show additional signs such as dystonic posturing and/or spasticity. Laboratory studies show intracellular accumulation of dihydroxyacetone phosphate (DHAP), particularly in red blood cells (summary by Fermo et al., 2010). (615512)

UniProtKB/Swiss-Prot : 76 Triosephosphate isomerase deficiency: An autosomal recessive multisystem disorder characterized by congenital hemolytic anemia, progressive neuromuscular dysfunction, susceptibility to bacterial infection, and cardiomyopathy.

Wikipedia : 77 Triosephosphate isomerase deficiency is a rare autosomal recessivemetabolic disorder which was initially... more...

Related Diseases for Triosephosphate Isomerase Deficiency

Diseases related to Triosephosphate Isomerase Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 hemolytic anemia 10.4
2 myopathy 10.1
3 neuromuscular disease 10.1
4 congenital hemolytic anemia 10.1
5 axonal neuropathy 10.1
6 neuropathy 10.1
7 hypotonia 10.1

Graphical network of the top 20 diseases related to Triosephosphate Isomerase Deficiency:



Diseases related to Triosephosphate Isomerase Deficiency

Symptoms & Phenotypes for Triosephosphate Isomerase Deficiency

Human phenotypes related to Triosephosphate Isomerase Deficiency:

60 33 (show all 28)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 muscular hypotonia 60 33 hallmark (90%) Very frequent (99-80%) HP:0001252
2 skeletal muscle atrophy 60 33 hallmark (90%) Very frequent (99-80%) HP:0003202
3 abnormality of immune system physiology 60 33 hallmark (90%) Very frequent (99-80%) HP:0010978
4 central nervous system degeneration 60 33 hallmark (90%) Very frequent (99-80%) HP:0007009
5 diaphragmatic paralysis 60 33 frequent (33%) Frequent (79-30%) HP:0006597
6 hypertrophic cardiomyopathy 60 33 occasional (7.5%) Occasional (29-5%) HP:0001639
7 decreased nerve conduction velocity 60 33 occasional (7.5%) Occasional (29-5%) HP:0000762
8 optic disc pallor 33 occasional (7.5%) HP:0000543
9 spasticity 33 HP:0001257
10 tremor 33 HP:0001337
11 kyphosis 33 HP:0002808
12 global developmental delay 33 HP:0001263
13 splenomegaly 33 HP:0001744
14 myopathy 33 HP:0003198
15 respiratory insufficiency due to muscle weakness 33 HP:0002747
16 peripheral neuropathy 33 HP:0009830
17 congestive heart failure 33 HP:0001635
18 dystonia 33 HP:0001332
19 cholelithiasis 33 HP:0001081
20 jaundice 33 HP:0000952
21 chronic hemolytic anemia 33 HP:0004870
22 hyporeflexia 33 HP:0001265
23 cholecystitis 33 HP:0001082
24 generalized hypotonia 33 HP:0001290
25 progressive muscle weakness 33 HP:0003323
26 unsteady gait 33 HP:0002317
27 normocytic anemia 33 HP:0001897
28 normochromic anemia 33 HP:0001895

Symptoms via clinical synopsis from OMIM:

58
Neurologic Central Nervous System:
spasticity
tremor
dystonia
hypotonia
gait instability
more
Respiratory:
respiratory insufficiency due to muscle weakness

Skin Nails Hair Skin:
jaundice

Immunology:
increased susceptibility to infections

Head And Neck Eyes:
pale optic discs (1 family)

Skeletal Spine:
kyphosis

Neurologic Peripheral Nervous System:
peripheral neuropathy
hyporeflexia

Muscle Soft Tissue:
hypotonia
muscle atrophy
muscle weakness, progressive

Hematology:
hemolytic anemia, chronic

Laboratory Abnormalities:
increased levels of dihydroxyacetone phosphate (dhap) in tissues and red cells
decreased activity of triosephosphate isomerase

Clinical features from OMIM:

615512

UMLS symptoms related to Triosephosphate Isomerase Deficiency:


tremor, abnormal pyramidal signs, icterus, muscle spasticity

MGI Mouse Phenotypes related to Triosephosphate Isomerase Deficiency:

47
# Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 8.92 GLO1 PREP SPSB2 TPI1

Drugs & Therapeutics for Triosephosphate Isomerase Deficiency

Search Clinical Trials , NIH Clinical Center for Triosephosphate Isomerase Deficiency

Genetic Tests for Triosephosphate Isomerase Deficiency

Genetic tests related to Triosephosphate Isomerase Deficiency:

# Genetic test Affiliating Genes
1 Triosephosphate Isomerase Deficiency 30 TPI1

Anatomical Context for Triosephosphate Isomerase Deficiency

MalaCards organs/tissues related to Triosephosphate Isomerase Deficiency:

42
Skin, Eye, Skeletal Muscle, Testes

Publications for Triosephosphate Isomerase Deficiency

Articles related to Triosephosphate Isomerase Deficiency:

(show all 38)
# Title Authors Year
1
Differential effects on enzyme stability and kinetic parameters of mutants related to human triosephosphate isomerase deficiency. ( 29571745 )
2018
2
Structural and Genetic Studies Demonstrate Neurologic Dysfunction in Triosephosphate Isomerase Deficiency Is Associated with Impaired Synaptic Vesicle Dynamics. ( 27031109 )
2016
3
Hemolytic anemia and progressive neurologic impairment: think about triosephosphate isomerase deficiency. ( 24840153 )
2014
4
Reappraisal of triosephosphate isomerase deficiency. ( 20546019 )
2011
5
Triosephosphate isomerase deficiency: a patient with Val231Met mutation. ( 21215915 )
2011
6
Triosephosphate isomerase deficiency: new insights into an enigmatic disease. ( 19786097 )
2009
7
Structural basis of human triosephosphate isomerase deficiency: mutation E104D is related to alterations of a conserved water network at the dimer interface. ( 18562316 )
2008
8
Novel human pathological mutations. Gene symbol: TPI1. Disease: triosephosphate isomerase deficiency. ( 17879449 )
2007
9
Triosephosphate isomerase deficiency: facts and doubts. ( 17424909 )
2006
10
Drosophila model of human inherited triosephosphate isomerase deficiency glycolytic enzymopathy. ( 16980388 )
2006
11
Triosephosphate isomerase deficiency: consequences of an inherited mutation at mRNA, protein and metabolic levels. ( 16086671 )
2005
12
Chronic axonal neuropathy with triosephosphate isomerase deficiency. ( 14984912 )
2004
13
Increased formation of methylglyoxal and protein glycation, oxidation and nitrosation in triosephosphate isomerase deficiency. ( 14559119 )
2003
14
Triosephosphate isomerase deficiency: a neurodegenerative misfolding disease. ( 12023819 )
2002
15
Triosephosphate isomerase deficiency. genetic, enzymatic and metabolic characterization of a new case from Spain. ( 11940494 )
2002
16
Triosephosphate isomerase deficiency: historical perspectives and molecular aspects. ( 10916682 )
2000
17
Triosephosphate isomerase deficiency with elevated sweat chloride test: report of a case. ( 11196750 )
2000
18
Towards enzyme-replacement treatment in triosephosphate isomerase deficiency. ( 10209987 )
1999
19
The feasibility of replacement therapy for inherited disorder of glycolysis: triosephosphate isomerase deficiency (review). ( 9850739 )
1998
20
Triosephosphate isomerase deficiency in a child with congenital hemolytic anemia and severe hypotonia. ( 9842650 )
1998
21
Search for the pathogenesis of the differing phenotype in two compound heterozygote Hungarian brothers with the same genotypic triosephosphate isomerase deficiency. ( 9294216 )
1997
22
Evidence for founder effect of the Glu104Asp substitution and identification of new mutations in triosephosphate isomerase deficiency. ( 9338582 )
1997
23
Prenatal diagnosis of triosephosphate isomerase deficiency. ( 8639817 )
1996
24
Triosephosphate isomerase deficiency: predictions and facts. ( 8944178 )
1996
25
Triosephosphate isomerase deficiency: repetitive occurrence of point mutation in amino acid 104 in multiple apparently unrelated families. ( 7485100 )
1995
26
Triosephosphate isomerase deficiency: biochemical and molecular genetic analysis for prenatal diagnosis. ( 7628118 )
1995
27
Human triosephosphate isomerase deficiency resulting from mutation of Phe-240. ( 8503454 )
1993
28
Triosephosphate isomerase deficiency: haemolytic anaemia, myopathy with altered mitochondria and mental retardation due to a new variant with accelerated enzyme catabolism and diminished specific activity. ( 1959537 )
1991
29
Platelet function defect in triosephosphate isomerase deficiency. ( 2946631 )
1986
30
Human triosephosphate isomerase cDNA and protein structure. Studies of triosephosphate isomerase deficiency in man. ( 2579079 )
1985
31
Neurological findings in triosephosphate isomerase deficiency. ( 4004168 )
1985
32
Triosephosphate isomerase deficiency: 2 new cases. ( 4012221 )
1985
33
Triosephosphate isomerase deficiency. A case report with neuropathological findings. ( 7114003 )
1982
34
Elevated frequency of carriers for triosephosphate isomerase deficiency in newborn infants. ( 7155666 )
1982
35
Triosephosphate isomerase deficiency with hemolytic anemia and severe neuromuscular disease: familial and biochemical studies of a case found in Spain. ( 669702 )
1978
36
Modification in a screening test for triosephosphate isomerase deficiency. ( 4639873 )
1972
37
Electrophoretic abnormality in triosephosphate isomerase deficiency. ( 5665870 )
1968
38
HEREDITARY HEMOLYTIC ANEMIA WITH TRIOSEPHOSPHATE ISOMERASE DEFICIENCY. ( 14242501 )
1965

Variations for Triosephosphate Isomerase Deficiency

UniProtKB/Swiss-Prot genetic disease variations for Triosephosphate Isomerase Deficiency:

76
# Symbol AA change Variation ID SNP ID
1 TPI1 p.Cys79Tyr VAR_007534 rs121964848
2 TPI1 p.Gly110Ala VAR_007535
3 TPI1 p.Glu142Asp VAR_007536 rs121964845
4 TPI1 p.Val192Met VAR_007538 rs188138723
5 TPI1 p.Ile208Val VAR_007539 rs121964849
6 TPI1 p.Val269Met VAR_007540
7 TPI1 p.Phe278Leu VAR_007541 rs121964847

ClinVar genetic disease variations for Triosephosphate Isomerase Deficiency:

6 (show top 50) (show all 54)
# Gene Variation Type Significance SNP ID Assembly Location
1 TPI1 NM_001159287.1(TPI1): c.426G> C (p.Glu142Asp) single nucleotide variant Pathogenic rs121964845 GRCh37 Chromosome 12, 6978338: 6978338
2 TPI1 NM_001159287.1(TPI1): c.426G> C (p.Glu142Asp) single nucleotide variant Pathogenic rs121964845 GRCh38 Chromosome 12, 6869174: 6869174
3 TPI1 NM_001159287.1(TPI1): c.832T> C (p.Phe278Leu) single nucleotide variant Pathogenic rs121964847 GRCh37 Chromosome 12, 6979518: 6979518
4 TPI1 NM_001159287.1(TPI1): c.832T> C (p.Phe278Leu) single nucleotide variant Pathogenic rs121964847 GRCh38 Chromosome 12, 6870354: 6870354
5 TPI1 NM_001159287.1(TPI1): c.236G> A (p.Cys79Tyr) single nucleotide variant Pathogenic rs121964848 GRCh37 Chromosome 12, 6978037: 6978037
6 TPI1 NM_001159287.1(TPI1): c.236G> A (p.Cys79Tyr) single nucleotide variant Pathogenic rs121964848 GRCh38 Chromosome 12, 6868873: 6868873
7 TPI1 NM_001159287.1(TPI1): c.622A> G (p.Ile208Val) single nucleotide variant Pathogenic rs121964849 GRCh37 Chromosome 12, 6978905: 6978905
8 TPI1 NM_001159287.1(TPI1): c.622A> G (p.Ile208Val) single nucleotide variant Pathogenic rs121964849 GRCh38 Chromosome 12, 6869741: 6869741
9 TPI1 NM_001159287.1(TPI1): c.547G> T (p.Glu183Ter) single nucleotide variant Pathogenic rs121964850 GRCh37 Chromosome 12, 6978533: 6978533
10 TPI1 NM_001159287.1(TPI1): c.547G> T (p.Glu183Ter) single nucleotide variant Pathogenic rs121964850 GRCh38 Chromosome 12, 6869369: 6869369
11 TPI1 NM_001159287.1(TPI1): c.833T> C (p.Phe278Ser) single nucleotide variant Pathogenic rs587777440 GRCh37 Chromosome 12, 6979519: 6979519
12 TPI1 NM_001159287.1(TPI1): c.833T> C (p.Phe278Ser) single nucleotide variant Pathogenic rs587777440 GRCh38 Chromosome 12, 6870355: 6870355
13 TPI1 NM_001159287.1(TPI1): c.143dup (p.Asn49Lysfs) duplication Pathogenic rs587777441 GRCh37 Chromosome 12, 6976762: 6976762
14 TPI1 NM_001159287.1(TPI1): c.143dup (p.Asn49Lysfs) duplication Pathogenic rs587777441 GRCh38 Chromosome 12, 6867598: 6867598
15 TPI1 NM_000365.5(TPI1): c.239+8C> A single nucleotide variant Uncertain significance rs782359362 GRCh38 Chromosome 12, 6868995: 6868995
16 TPI1 NM_000365.5(TPI1): c.239+8C> A single nucleotide variant Uncertain significance rs782359362 GRCh37 Chromosome 12, 6978159: 6978159
17 TPI1 NM_000365.5(TPI1): c.544-14G> A single nucleotide variant Likely benign rs72661109 GRCh38 Chromosome 12, 6870035: 6870035
18 TPI1 NM_000365.5(TPI1): c.544-14G> A single nucleotide variant Likely benign rs72661109 GRCh37 Chromosome 12, 6979199: 6979199
19 TPI1 NM_000365.5(TPI1): c.631+13G> A single nucleotide variant Likely benign rs60115912 GRCh38 Chromosome 12, 6870149: 6870149
20 TPI1 NM_000365.5(TPI1): c.631+13G> A single nucleotide variant Likely benign rs60115912 GRCh37 Chromosome 12, 6979313: 6979313
21 TPI1 NM_000365.5(TPI1): c.*178G> A single nucleotide variant Uncertain significance rs144171030 GRCh38 Chromosome 12, 6870561: 6870561
22 TPI1 NM_000365.5(TPI1): c.*178G> A single nucleotide variant Uncertain significance rs144171030 GRCh37 Chromosome 12, 6979725: 6979725
23 TPI1 NM_000365.5(TPI1): c.*341C> T single nucleotide variant Benign rs1804544 GRCh38 Chromosome 12, 6870724: 6870724
24 TPI1 NM_000365.5(TPI1): c.*341C> T single nucleotide variant Benign rs1804544 GRCh37 Chromosome 12, 6979888: 6979888
25 TPI1 NM_000365.5(TPI1): c.*542_*544delCAA deletion Uncertain significance rs782559646 GRCh38 Chromosome 12, 6870925: 6870927
26 TPI1 NM_000365.5(TPI1): c.*542_*544delCAA deletion Uncertain significance rs782559646 GRCh37 Chromosome 12, 6980089: 6980091
27 TPI1 NM_000365.5(TPI1): c.543+6C> T single nucleotide variant Uncertain significance rs369693539 GRCh38 Chromosome 12, 6869779: 6869779
28 TPI1 NM_000365.5(TPI1): c.543+6C> T single nucleotide variant Uncertain significance rs369693539 GRCh37 Chromosome 12, 6978943: 6978943
29 TPI1 NM_000365.5(TPI1): c.544-10C> G single nucleotide variant Likely benign rs115061797 GRCh38 Chromosome 12, 6870039: 6870039
30 TPI1 NM_000365.5(TPI1): c.544-10C> G single nucleotide variant Likely benign rs115061797 GRCh37 Chromosome 12, 6979203: 6979203
31 TPI1 NM_000365.5(TPI1): c.*69C> T single nucleotide variant Uncertain significance rs782061169 GRCh38 Chromosome 12, 6870452: 6870452
32 TPI1 NM_000365.5(TPI1): c.*69C> T single nucleotide variant Uncertain significance rs782061169 GRCh37 Chromosome 12, 6979616: 6979616
33 TPI1 NM_000365.5(TPI1): c.*239C> T single nucleotide variant Uncertain significance rs886049811 GRCh38 Chromosome 12, 6870622: 6870622
34 TPI1 NM_000365.5(TPI1): c.*239C> T single nucleotide variant Uncertain significance rs886049811 GRCh37 Chromosome 12, 6979786: 6979786
35 TPI1 NM_000365.5(TPI1): c.*420T> C single nucleotide variant Benign rs58194764 GRCh38 Chromosome 12, 6870803: 6870803
36 TPI1 NM_000365.5(TPI1): c.*420T> C single nucleotide variant Benign rs58194764 GRCh37 Chromosome 12, 6979967: 6979967
37 TPI1 NM_000365.5(TPI1): c.*541dupA duplication Uncertain significance rs201871949 GRCh38 Chromosome 12, 6870924: 6870924
38 TPI1 NM_000365.5(TPI1): c.*541dupA duplication Uncertain significance rs201871949 GRCh37 Chromosome 12, 6980088: 6980088
39 TPI1 NM_000365.5(TPI1): c.*260G> A single nucleotide variant Uncertain significance rs782764628 GRCh38 Chromosome 12, 6870643: 6870643
40 TPI1 NM_000365.5(TPI1): c.*260G> A single nucleotide variant Uncertain significance rs782764628 GRCh37 Chromosome 12, 6979807: 6979807
41 TPI1 NM_000365.5(TPI1): c.-29C> T single nucleotide variant Uncertain significance rs181882616 GRCh38 Chromosome 12, 6867538: 6867538
42 TPI1 NM_000365.5(TPI1): c.-29C> T single nucleotide variant Uncertain significance rs181882616 GRCh37 Chromosome 12, 6976702: 6976702
43 TPI1 NM_000365.5(TPI1): c.-11G> A single nucleotide variant Uncertain significance rs199634350 GRCh38 Chromosome 12, 6867556: 6867556
44 TPI1 NM_000365.5(TPI1): c.-11G> A single nucleotide variant Uncertain significance rs199634350 GRCh37 Chromosome 12, 6976720: 6976720
45 TPI1 NM_000365.5(TPI1): c.261C> T (p.Cys87=) single nucleotide variant Uncertain significance rs370863694 GRCh38 Chromosome 12, 6869120: 6869120
46 TPI1 NM_000365.5(TPI1): c.261C> T (p.Cys87=) single nucleotide variant Uncertain significance rs370863694 GRCh37 Chromosome 12, 6978284: 6978284
47 TPI1 NM_000365.5(TPI1): c.321T> C (p.Asp107=) single nucleotide variant Likely benign rs141972556 GRCh38 Chromosome 12, 6869180: 6869180
48 TPI1 NM_000365.5(TPI1): c.321T> C (p.Asp107=) single nucleotide variant Likely benign rs141972556 GRCh37 Chromosome 12, 6978344: 6978344
49 TPI1 NM_000365.5(TPI1): c.543+5C> G single nucleotide variant Uncertain significance rs782153322 GRCh38 Chromosome 12, 6869778: 6869778
50 TPI1 NM_000365.5(TPI1): c.543+5C> G single nucleotide variant Uncertain significance rs782153322 GRCh37 Chromosome 12, 6978942: 6978942

Expression for Triosephosphate Isomerase Deficiency

Search GEO for disease gene expression data for Triosephosphate Isomerase Deficiency.

Pathways for Triosephosphate Isomerase Deficiency

GO Terms for Triosephosphate Isomerase Deficiency

Cellular components related to Triosephosphate Isomerase Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytosol GO:0005829 8.92 GLO1 PREP SPSB2 TPI1

Sources for Triosephosphate Isomerase Deficiency

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