MTDPS2
MCID: MTC062
MIFTS: 33

Mitochondrial Dna Depletion Syndrome 2 (MTDPS2)

Categories: Bone diseases, Cardiovascular diseases, Ear diseases, Eye diseases, Gastrointestinal diseases, Genetic diseases, Liver diseases, Metabolic diseases, Muscle diseases, Nephrological diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Mitochondrial Dna Depletion Syndrome 2

MalaCards integrated aliases for Mitochondrial Dna Depletion Syndrome 2:

Name: Mitochondrial Dna Depletion Syndrome 2 58 12 76 30 13 6 74
Mtdps2 58 76
Mitochondrial Dna Depletion Syndrome 2 Myopathic Type 76
Mitochondrial Dna Depletion Syndrome, Myopathic Form 60
Mitochondrial Dna Depletion Myopathy, Tk2-Related 58
Mitochondrial Dna Depletion Myopathy Tk2-Related 76
Myopathic Mitochondrial Dna Depletion Syndrome 76
Mitochondrial Dna Depletion Syndrome, Type 2 41
Mtdna Depletion Syndrome, Myopathic Form 60

Characteristics:

Orphanet epidemiological data:

60
mitochondrial dna depletion syndrome, myopathic form
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
variable severity
progressive disorder
later onset has been reported
onset usually by age 2 years


HPO:

33
mitochondrial dna depletion syndrome 2:
Onset and clinical course variable expressivity infantile onset progressive
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Mitochondrial Dna Depletion Syndrome 2

OMIM : 58 Mitochondrial DNA depletion syndrome-2 is an autosomal recessive disorder characterized primarily by childhood onset of muscle weakness associated with depletion of mtDNA in skeletal muscle. There is wide clinical variability; some patients have onset in infancy and show a rapidly progressive course with early death due to respiratory failure, whereas others have later childhood onset of a slowly progressive myopathy (Oskoui et al., 2006). For a discussion of genetic heterogeneity of autosomal recessive mtDNA depletion syndromes, see MTDPS1 (603041). (609560)

MalaCards based summary : Mitochondrial Dna Depletion Syndrome 2, also known as mtdps2, is related to tk2-related mitochondrial dna depletion syndrome, myopathic form and tk2-related mitochondrial dna maintenance defect, myopathic form. An important gene associated with Mitochondrial Dna Depletion Syndrome 2 is TK2 (Thymidine Kinase 2). Affiliated tissues include skeletal muscle, liver and bone, and related phenotypes are myopathy and motor deterioration

UniProtKB/Swiss-Prot : 76 Mitochondrial DNA depletion syndrome 2: A disorder due to mitochondrial dysfunction characterized by childhood onset of muscle weakness associated with depletion of mtDNA in skeletal muscle. There is wide clinical variability; some patients have onset in infancy and show a rapidly progressive course with early death due to respiratory failure, whereas others have later onset of a slowly progressive myopathy.

Related Diseases for Mitochondrial Dna Depletion Syndrome 2

Symptoms & Phenotypes for Mitochondrial Dna Depletion Syndrome 2

Human phenotypes related to Mitochondrial Dna Depletion Syndrome 2:

60 33 (show top 50) (show all 59)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 myopathy 60 33 obligate (100%) Obligate (100%) HP:0003198
2 motor deterioration 60 33 hallmark (90%) Very frequent (99-80%) HP:0002333
3 generalized hypotonia 60 33 hallmark (90%) Very frequent (99-80%) HP:0001290
4 developmental regression 60 33 frequent (33%) Frequent (79-30%) HP:0002376
5 feeding difficulties in infancy 60 33 frequent (33%) Frequent (79-30%) HP:0008872
6 respiratory insufficiency due to muscle weakness 60 33 frequent (33%) Frequent (79-30%) HP:0002747
7 generalized muscle weakness 60 33 frequent (33%) Frequent (79-30%) HP:0003324
8 respiratory distress 60 33 frequent (33%) Frequent (79-30%) HP:0002098
9 failure to thrive in infancy 60 33 frequent (33%) Frequent (79-30%) HP:0001531
10 motor delay 60 33 frequent (33%) Frequent (79-30%) HP:0001270
11 chronic fatigue 60 33 frequent (33%) Frequent (79-30%) HP:0012432
12 respiratory failure 60 33 frequent (33%) Frequent (79-30%) HP:0002878
13 recurrent pneumonia 60 33 frequent (33%) Frequent (79-30%) HP:0006532
14 difficulty walking 60 33 frequent (33%) Frequent (79-30%) HP:0002355
15 hyporeflexia 60 33 frequent (33%) Frequent (79-30%) HP:0001265
16 exercise intolerance 60 33 frequent (33%) Frequent (79-30%) HP:0003546
17 progressive proximal muscle weakness 60 33 frequent (33%) Frequent (79-30%) HP:0009073
18 distal muscle weakness 60 33 frequent (33%) Frequent (79-30%) HP:0002460
19 difficulty standing 60 33 frequent (33%) Frequent (79-30%) HP:0003698
20 infantile encephalopathy 60 33 frequent (33%) Frequent (79-30%) HP:0007105
21 generalized-onset seizure 33 frequent (33%) HP:0002197
22 dysarthria 60 33 occasional (7.5%) Occasional (29-5%) HP:0001260
23 dysphagia 60 33 occasional (7.5%) Occasional (29-5%) HP:0002015
24 myalgia 60 33 occasional (7.5%) Occasional (29-5%) HP:0003326
25 progressive external ophthalmoplegia 60 33 occasional (7.5%) Occasional (29-5%) HP:0000590
26 severe sensorineural hearing impairment 60 33 occasional (7.5%) Occasional (29-5%) HP:0008625
27 bulbar palsy 60 33 occasional (7.5%) Occasional (29-5%) HP:0001283
28 bilateral ptosis 60 33 occasional (7.5%) Occasional (29-5%) HP:0001488
29 ventilator dependence with inability to wean 60 33 occasional (7.5%) Occasional (29-5%) HP:0005946
30 infantile sensorineural hearing impairment 60 33 occasional (7.5%) Occasional (29-5%) HP:0008610
31 weakness of facial musculature 60 33 occasional (7.5%) Occasional (29-5%) HP:0030319
32 scoliosis 60 33 very rare (1%) Very rare (<4-1%) HP:0002650
33 spinal muscular atrophy 60 33 very rare (1%) Very rare (<4-1%) HP:0007269
34 muscular hypotonia 60 33 Frequent (79-30%) HP:0001252
35 seizures 33 HP:0001250
36 muscle weakness 60 Very frequent (99-80%)
37 respiratory insufficiency 60 Very frequent (99-80%)
38 hearing impairment 33 HP:0000365
39 cognitive impairment 60 Excluded (0%)
40 aminoaciduria 33 HP:0003355
41 skeletal muscle atrophy 60 Frequent (79-30%)
42 irritability 33 HP:0000737
43 emg: myopathic abnormalities 33 HP:0003458
44 ophthalmoparesis 60 Occasional (29-5%)
45 lactic acidosis 33 HP:0003128
46 ragged-red muscle fibers 33 HP:0003200
47 intellectual disability, progressive 33 HP:0006887
48 generalized seizures 60 Frequent (79-30%)
49 facial diplegia 33 HP:0001349
50 limb muscle weakness 33 HP:0003690

Symptoms via clinical synopsis from OMIM:

58
Laboratory Abnormalities:
aminoaciduria
increased serum creatine kinase

Muscle Soft Tissue:
inability to walk
limb muscle weakness
gowers sign
loss of ability to walk in early childhood
hypotonia
more
Head And Neck Face:
facial diplegia

Respiratory:
respiratory insufficiency due to muscle weakness

Metabolic Features:
lactic acidosis

Clinical features from OMIM:

609560

Drugs & Therapeutics for Mitochondrial Dna Depletion Syndrome 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Treatment of TK2 Deficiency With Thymidine and Deoxycytidine Enrolling by invitation NCT03639701 Phase 1, Phase 2 Thymidine

Search NIH Clinical Center for Mitochondrial Dna Depletion Syndrome 2

Genetic Tests for Mitochondrial Dna Depletion Syndrome 2

Genetic tests related to Mitochondrial Dna Depletion Syndrome 2:

# Genetic test Affiliating Genes
1 Mitochondrial Dna Depletion Syndrome 2 30 TK2

Anatomical Context for Mitochondrial Dna Depletion Syndrome 2

MalaCards organs/tissues related to Mitochondrial Dna Depletion Syndrome 2:

42
Skeletal Muscle, Liver, Bone, Eye

Publications for Mitochondrial Dna Depletion Syndrome 2

Articles related to Mitochondrial Dna Depletion Syndrome 2:

# Title Authors Year
1
TK2 mutation presenting as indolent myopathy. ( 23303857 )
2013
2
Adult cases of mitochondrial DNA depletion due to TK2 defect: an expanding spectrum. ( 22345218 )
2012
3
Mitochondrial myopathy of childhood associated with mitochondrial DNA depletion and a homozygous mutation (T77M) in the TK2 gene. ( 12873860 )
2003
4
Kinetic properties of mutant human thymidine kinase 2 suggest a mechanism for mitochondrial DNA depletion myopathy. ( 12493767 )
2003
5
Mitochondrial DNA depletion: mutations in thymidine kinase gene with myopathy and SMA. ( 12391347 )
2002
6
Mutant mitochondrial thymidine kinase in mitochondrial DNA depletion myopathy. ( 11687801 )
2001
7
Mitochondrial myopathy of childhood associated with depletion of mitochondrial DNA. ( 1734306 )
1992

Variations for Mitochondrial Dna Depletion Syndrome 2

UniProtKB/Swiss-Prot genetic disease variations for Mitochondrial Dna Depletion Syndrome 2:

76
# Symbol AA change Variation ID SNP ID
1 TK2 p.Ile53Met VAR_019419 rs137854432
2 TK2 p.Thr108Met VAR_019420 rs137854431
3 TK2 p.His121Asn VAR_019421 rs137854429
4 TK2 p.Ile212Asn VAR_019422 rs137854430
5 TK2 p.Thr64Met VAR_023790 rs281865487
6 TK2 p.Arg183Trp VAR_023791 rs137886900
7 TK2 p.Arg192Lys VAR_023792 rs281865496
8 TK2 p.Met117Val VAR_072789
9 TK2 p.Ala139Val VAR_072790 rs281865494

ClinVar genetic disease variations for Mitochondrial Dna Depletion Syndrome 2:

6 (show top 50) (show all 70)
# Gene Variation Type Significance SNP ID Assembly Location
1 TK2 NM_004614.4(TK2): c.361C> A (p.His121Asn) single nucleotide variant Pathogenic rs137854429 GRCh37 Chromosome 16, 66565297: 66565297
2 TK2 NM_004614.4(TK2): c.361C> A (p.His121Asn) single nucleotide variant Pathogenic rs137854429 GRCh38 Chromosome 16, 66531394: 66531394
3 TK2 NM_004614.4(TK2): c.635T> A (p.Ile212Asn) single nucleotide variant Pathogenic rs137854430 GRCh37 Chromosome 16, 66547698: 66547698
4 TK2 NM_004614.4(TK2): c.635T> A (p.Ile212Asn) single nucleotide variant Pathogenic rs137854430 GRCh38 Chromosome 16, 66513795: 66513795
5 TK2 NM_004614.4(TK2): c.323C> T (p.Thr108Met) single nucleotide variant Pathogenic rs137854431 GRCh37 Chromosome 16, 66565335: 66565335
6 TK2 NM_004614.4(TK2): c.323C> T (p.Thr108Met) single nucleotide variant Pathogenic rs137854431 GRCh38 Chromosome 16, 66531432: 66531432
7 TK2 NM_004614.4(TK2): c.159C> G (p.Ile53Met) single nucleotide variant Pathogenic rs137854432 GRCh37 Chromosome 16, 66575854: 66575854
8 TK2 NM_004614.4(TK2): c.159C> G (p.Ile53Met) single nucleotide variant Pathogenic rs137854432 GRCh38 Chromosome 16, 66541951: 66541951
9 TK2 NM_004614.4(TK2): c.218_219dupCG (p.Thr74Argfs) duplication Pathogenic rs281865505 GRCh37 Chromosome 16, 66575794: 66575795
10 TK2 NM_004614.4(TK2): c.218_219dupCG (p.Thr74Argfs) duplication Pathogenic rs281865505 GRCh38 Chromosome 16, 66541891: 66541892
11 TK2 NM_004614.4: c.-270+2561delins;7287-7335inv insertion Pathogenic
12 TK2 NM_001040138.2(CKLF): c.-7863_-2035delinsoAC010542.7: g.65062_65110 indel Pathogenic GRCh37 Chromosome 16, 66578756: 66584584
13 TK2 NM_001040138.2(CKLF): c.-7863_-2035delinsoAC010542.7: g.65062_65110 indel Pathogenic GRCh38 Chromosome 16, 66544853: 66550681
14 TK2 NM_004614.4(TK2): c.129_132delAGAA (p.Lys43Asnfs) deletion Pathogenic rs281865500 GRCh37 Chromosome 16, 66582905: 66582908
15 TK2 NM_004614.4(TK2): c.129_132delAGAA (p.Lys43Asnfs) deletion Pathogenic rs281865500 GRCh38 Chromosome 16, 66549002: 66549005
16 TK2 NM_004614.4(TK2): c.133C> T (p.Gln45Ter) single nucleotide variant Pathogenic rs281865486 GRCh37 Chromosome 16, 66582904: 66582904
17 TK2 NM_004614.4(TK2): c.133C> T (p.Gln45Ter) single nucleotide variant Pathogenic rs281865486 GRCh38 Chromosome 16, 66549001: 66549001
18 TK2 NM_004614.4(TK2): c.142dupG (p.Glu48Glyfs) duplication Pathogenic rs281865503 GRCh37 Chromosome 16, 66582895: 66582895
19 TK2 NM_004614.4(TK2): c.142dupG (p.Glu48Glyfs) duplication Pathogenic rs281865503 GRCh38 Chromosome 16, 66548992: 66548992
20 TK2 NM_004614.4(TK2): c.150dupA (p.Ser51Ilefs) duplication Pathogenic rs281865504 GRCh37 Chromosome 16, 66582887: 66582887
21 TK2 NM_004614.4(TK2): c.150dupA (p.Ser51Ilefs) duplication Pathogenic rs281865504 GRCh38 Chromosome 16, 66548984: 66548984
22 TK2 NM_004614.4(TK2): c.156+2T> C single nucleotide variant Pathogenic rs281865499 GRCh37 Chromosome 16, 66582879: 66582879
23 TK2 NM_004614.4(TK2): c.156+2T> C single nucleotide variant Pathogenic rs281865499 GRCh38 Chromosome 16, 66548976: 66548976
24 TK2 NM_004614.4(TK2): c.173A> G (p.Asn58Ser) single nucleotide variant Pathogenic/Likely pathogenic rs138439950 GRCh37 Chromosome 16, 66575840: 66575840
25 TK2 NM_004614.4(TK2): c.173A> G (p.Asn58Ser) single nucleotide variant Pathogenic/Likely pathogenic rs138439950 GRCh38 Chromosome 16, 66541937: 66541937
26 TK2 NM_004614.4(TK2): c.191C> T (p.Thr64Met) single nucleotide variant Pathogenic rs281865487 GRCh37 Chromosome 16, 66575822: 66575822
27 TK2 NM_004614.4(TK2): c.191C> T (p.Thr64Met) single nucleotide variant Pathogenic rs281865487 GRCh38 Chromosome 16, 66541919: 66541919
28 TK2 NM_004614.4(TK2): c.198C> G (p.Cys66Trp) single nucleotide variant Pathogenic rs281865488 GRCh37 Chromosome 16, 66575815: 66575815
29 TK2 NM_004614.4(TK2): c.198C> G (p.Cys66Trp) single nucleotide variant Pathogenic rs281865488 GRCh38 Chromosome 16, 66541912: 66541912
30 TK2 NM_004614.4(TK2): c.268C> T (p.Arg90Cys) single nucleotide variant Likely pathogenic rs281865489 GRCh37 Chromosome 16, 66570884: 66570884
31 TK2 NM_004614.4(TK2): c.268C> T (p.Arg90Cys) single nucleotide variant Likely pathogenic rs281865489 GRCh38 Chromosome 16, 66536981: 66536981
32 TK2 NM_004614.4(TK2): c.278A> G (p.Asn93Ser) single nucleotide variant Pathogenic rs142291440 GRCh37 Chromosome 16, 66570874: 66570874
33 TK2 NM_004614.4(TK2): c.278A> G (p.Asn93Ser) single nucleotide variant Pathogenic rs142291440 GRCh38 Chromosome 16, 66536971: 66536971
34 TK2 NM_004614.4(TK2): c.334T> A (p.Tyr112Asn) single nucleotide variant Pathogenic rs281865490 GRCh37 Chromosome 16, 66565324: 66565324
35 TK2 NM_004614.4(TK2): c.334T> A (p.Tyr112Asn) single nucleotide variant Pathogenic rs281865490 GRCh38 Chromosome 16, 66531421: 66531421
36 TK2 NM_004614.4(TK2): c.335_336dupAT (p.Val113Metfs) duplication Pathogenic rs281865506 GRCh37 Chromosome 16, 66565322: 66565323
37 TK2 NM_004614.4(TK2): c.335_336dupAT (p.Val113Metfs) duplication Pathogenic rs281865506 GRCh38 Chromosome 16, 66531419: 66531420
38 TK2 NM_004614.4(TK2): c.360_361delGCinsAA (p.His121Asn) indel Pathogenic rs281865507 GRCh37 Chromosome 16, 66565297: 66565298
39 TK2 NM_004614.4(TK2): c.360_361delGCinsAA (p.His121Asn) indel Pathogenic rs281865507 GRCh38 Chromosome 16, 66531394: 66531395
40 TK2 NM_004614.4(TK2): c.373C> T (p.Gln125Ter) single nucleotide variant Pathogenic rs281865491 GRCh37 Chromosome 16, 66565285: 66565285
41 TK2 NM_004614.4(TK2): c.373C> T (p.Gln125Ter) single nucleotide variant Pathogenic rs281865491 GRCh38 Chromosome 16, 66531382: 66531382
42 TK2 NM_004614.4(TK2): c.388C> T (p.Arg130Trp) single nucleotide variant Pathogenic rs281865493 GRCh37 Chromosome 16, 66562958: 66562958
43 TK2 NM_004614.4(TK2): c.388C> T (p.Arg130Trp) single nucleotide variant Pathogenic rs281865493 GRCh38 Chromosome 16, 66529055: 66529055
44 TK2 NM_004614.4(TK2): c.389G> A (p.Arg130Gln) single nucleotide variant Pathogenic rs281865492 GRCh37 Chromosome 16, 66562957: 66562957
45 TK2 NM_004614.4(TK2): c.389G> A (p.Arg130Gln) single nucleotide variant Pathogenic rs281865492 GRCh38 Chromosome 16, 66529054: 66529054
46 TK2 NM_004614.4(TK2): c.416C> T (p.Ala139Val) single nucleotide variant Pathogenic/Likely pathogenic rs281865494 GRCh37 Chromosome 16, 66562930: 66562930
47 TK2 NM_004614.4(TK2): c.8dupT (p.Trp4Valfs) duplication Pathogenic rs281865502 GRCh37 Chromosome 16, 66583957: 66583957
48 TK2 NM_004614.4(TK2): c.8dupT (p.Trp4Valfs) duplication Pathogenic rs281865502 GRCh38 Chromosome 16, 66550054: 66550054
49 TK2 NM_004614.4(TK2): c.416C> T (p.Ala139Val) single nucleotide variant Pathogenic/Likely pathogenic rs281865494 GRCh38 Chromosome 16, 66529027: 66529027
50 TK2 NM_004614.4(TK2): c.547C> G (p.Arg183Gly) single nucleotide variant Pathogenic rs137886900 GRCh37 Chromosome 16, 66551110: 66551110

Expression for Mitochondrial Dna Depletion Syndrome 2

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Pathways for Mitochondrial Dna Depletion Syndrome 2

GO Terms for Mitochondrial Dna Depletion Syndrome 2

Sources for Mitochondrial Dna Depletion Syndrome 2

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