MCID: MTC061
MIFTS: 35

Mitochondrial Dna Depletion Syndrome 1

Categories: Genetic diseases, Neuronal diseases, Gastrointestinal diseases, Metabolic diseases

Aliases & Classifications for Mitochondrial Dna Depletion Syndrome 1

MalaCards integrated aliases for Mitochondrial Dna Depletion Syndrome 1:

Name: Mitochondrial Dna Depletion Syndrome 1 53 12 28 13
Polip Syndrome 53 71
Mtdps1 53 71
Polyneuropathy, Ophthalmoplegia, Leukoencephalopathy, and Intestinal Pseudoobstruction 53
Polyneuropathy Ophthalmoplegia Leukoencephalopathy and Intestinal Pseudoobstruction 71
Mitochondrial Neurogastrointestinal Encephalopathy Syndrome, Tymp-Related 53
Mitochondrial Neurogastrointestinal Encephalopathy Syndrome Tymp-Related 71
Mitochondrial Neurogastrointestinal Encephalopathy Syndrome 69
Mitochondrial Neurogastrointestinal Encephalomyopathy 71
Mitochondrial Dna Depletion Syndrome 1, Mngie Type 71
Myoneurogastrointestinal Encephalopathy Syndrome 53
Myoneurogastrointestinal Encephalomyopathy 71
Mngie, Tymp-Related 53

Characteristics:

OMIM:

53
Inheritance:
autosomal recessive

Miscellaneous:
progressive disorder
onset in second to fifth decade
early death in early adulthood often associated with diverticulitis and intestinal perforation


HPO:

31
mitochondrial dna depletion syndrome 1:
Mortality/Aging death in early adulthood
Onset and clinical course progressive
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Mitochondrial Dna Depletion Syndrome 1

OMIM : 53 Mitochondrial DNA depletion syndrome-1 (MTDPS1) is an autosomal recessive progressive multisystem disorder clinically characterized by onset between the second and fifth decades of life of ptosis, progressive external ophthalmoplegia (PEO), gastrointestinal dysmotility (often pseudoobstruction), cachexia, diffuse leukoencephalopathy, peripheral neuropathy, and mitochondrial dysfunction. Mitochondrial DNA abnormalities can include depletion, deletion, and point mutations (Taanman et al., 2009). (603041)

MalaCards based summary : Mitochondrial Dna Depletion Syndrome 1, also known as polip syndrome, is related to mitochondrial neurogastrointestinal encephalomyopathy and mitochondrial neurogastrointestinal encephalopathy disease, and has symptoms including constipation, cachexia and abdominal pain. An important gene associated with Mitochondrial Dna Depletion Syndrome 1 is TYMP (Thymidine Phosphorylase). The drugs Cysteamine and Acetylcysteine have been mentioned in the context of this disorder.

UniProtKB/Swiss-Prot : 71 Mitochondrial DNA depletion syndrome 1, MNGIE type: A multisystem disease associated with mitochondrial dysfunction. It is clinically characterized by onset between the second and fifth decades of life, ptosis, progressive external ophthalmoplegia, gastrointestinal dysmotility (often pseudoobstruction), diffuse leukoencephalopathy, cachexia, peripheral neuropathy, and myopathy.

Related Diseases for Mitochondrial Dna Depletion Syndrome 1

Diseases related to Mitochondrial Dna Depletion Syndrome 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 36)
# Related Disease Score Top Affiliating Genes
1 mitochondrial neurogastrointestinal encephalomyopathy 32.8 MT-TK POLG TYMP
2 mitochondrial neurogastrointestinal encephalopathy disease 31.4 POLG TYMP
3 mitochondrial dna depletion syndrome 4a 30.6 POLG TYMP
4 encephalomyopathy 11.0
5 mitochondrial dna depletion syndrome 9 10.8
6 mitochondrial dna depletion syndrome 3 10.8
7 mitochondrial dna depletion syndrome 6 10.8
8 mitochondrial dna depletion syndrome 7 10.8
9 mitochondrial dna depletion syndrome 2 10.8
10 mitochondrial dna depletion syndrome 5 10.8
11 mitochondrial dna depletion syndrome 8a 10.8
12 mitochondrial dna depletion syndrome 4b 10.8
13 mitochondrial dna depletion syndrome 11 10.8
14 mitochondrial dna depletion syndrome 12b , autosomal recessive 10.8
15 mitochondrial dna depletion syndrome 13 10.8
16 mitochondrial dna depletion syndrome 12a , autosomal dominant 10.8
17 bulimia nervosa 2 10.2
18 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 10.2
19 hypogonadism 10.2
20 peritonitis 10.2
21 trigeminal neuralgia 10.1
22 endocarditis 10.1
23 esophagitis 10.1
24 eating disorder 10.1
25 polyneuropathy 9.9
26 intestinal pseudo-obstruction 9.9
27 paralytic ileus 9.8 MT-TK TYMP
28 neonatal period electroclinical syndrome 9.6 MT-TK POLG
29 ocular motility disease 9.5 POLG TYMP
30 mitochondrial metabolism disease 9.5 MT-TK POLG
31 leigh syndrome 9.4 MT-TK POLG
32 chronic progressive external ophthalmoplegia 9.3 MT-TK POLG TYMP
33 3-methylglutaconic aciduria, type v 9.3 MT-TK POLG TYMP
34 mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes 9.3 MT-TK POLG TYMP
35 kearns-sayre syndrome 9.3 MT-TK POLG TYMP
36 mitochondrial disorders 9.3 MT-TK POLG TYMP

Graphical network of the top 20 diseases related to Mitochondrial Dna Depletion Syndrome 1:



Diseases related to Mitochondrial Dna Depletion Syndrome 1

Symptoms & Phenotypes for Mitochondrial Dna Depletion Syndrome 1

Symptoms via clinical synopsis from OMIM:

53
Abdomen Gastroin testinal:
abdominal pain
vomiting
intermittent diarrhea
malabsorption
gastroparesis
more
Neurologic Peripheral Nervous System:
peripheral neuropathy
areflexia
loss of distal sensation
sensorimotor axonal/demyelinating neuropathy

Muscle Soft Tissue:
mitochondrial myopathy
ragged red fibers seen on muscle biopsy
distal limb muscle weakness (less common)
multiple mitochondrial dna (mtdna) deletions seen on muscle biopsy
distal limb muscle atrophy (less common)
more
Head And Neck Ears:
hearing loss, sensorineural

Growth Weight:
weight loss, progressive

Head And Neck Eyes:
ptosis
external ophthalmoplegia, progressive (peo)

Metabolic Features:
lactic acidosis

Neurologic Central Nervous System:
leukoencephalopathy
hypodensity of cerebral white matter seen on mri

Growth Other:
thin body habitus
marked cachexia

Laboratory Abnormalities:
decreased activity of thymidine phosphorylase
increased serum thymidine
increased serum deoxyuridine


Clinical features from OMIM:

603041

Human phenotypes related to Mitochondrial Dna Depletion Syndrome 1:

31 (show all 24)
# Description HPO Frequency HPO Source Accession
1 constipation 31 HP:0002019
2 cachexia 31 HP:0004326
3 abdominal pain 31 HP:0002027
4 vomiting 31 HP:0002013
5 intermittent diarrhea 31 HP:0002254
6 ptosis 31 HP:0000508
7 malabsorption 31 HP:0002024
8 sensorineural hearing impairment 31 HP:0000407
9 gastroparesis 31 HP:0002578
10 lactic acidosis 31 HP:0003128
11 ragged-red muscle fibers 31 HP:0003200
12 mitochondrial myopathy 31 HP:0003737
13 progressive external ophthalmoplegia 31 HP:0000590
14 areflexia 31 HP:0001284
15 distal muscle weakness 31 HP:0002460
16 hypointensity of cerebral white matter on mri 31 HP:0007103
17 distal sensory impairment 31 HP:0002936
18 distal amyotrophy 31 HP:0003693
19 malnutrition 31 HP:0004395
20 gastrointestinal dysmotility 31 HP:0002579
21 leukoencephalopathy 31 HP:0002352
22 subsarcolemmal accumulations of abnormally shaped mitochondria 31 HP:0003548
23 cytochrome c oxidase-negative muscle fibers 31 HP:0003688
24 multiple mitochondrial dna deletions 31 HP:0003689

UMLS symptoms related to Mitochondrial Dna Depletion Syndrome 1:


chronic constipation, intermittent diarrhea, vomiting, abdominal pain

Drugs & Therapeutics for Mitochondrial Dna Depletion Syndrome 1

Drugs for Mitochondrial Dna Depletion Syndrome 1 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 23)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Cysteamine Approved, Investigational Phase 2 60-23-1 6058
2
Acetylcysteine Approved, Investigational Phase 2 616-91-1 12035
3
alemtuzumab Approved, Investigational Phase 2 216503-57-0
4
Busulfan Approved, Investigational Phase 2 55-98-1 2478
5
Celecoxib Approved, Investigational Phase 2 169590-42-5 2662
6
Fludarabine Approved Phase 2 21679-14-1, 75607-67-9 30751
7
rituximab Approved Phase 2 174722-31-7 10201696
8 Thiotepa Approved, Investigational Phase 2 52-24-4 5453
9 Tocopherol Approved, Investigational, Nutraceutical Phase 2
10
Vitamin E Approved, Nutraceutical, Vet_approved Phase 2 59-02-9 14985
11 Alkylating Agents Phase 2
12 Antilymphocyte Serum Phase 2
13 Antimetabolites Phase 2
14 Antimetabolites, Antineoplastic Phase 2
15 Immunosuppressive Agents Phase 2
16 N-monoacetylcystine Phase 2
17 Thioctic Acid Phase 2
18 Tocopherols Phase 2
19 Tocotrienols Phase 2
20 Vitamins Phase 2
21 Alpha-lipoic Acid Nutraceutical Phase 2
22 Tocotrienol Investigational, Nutraceutical Phase 2 6829-55-6
23 Ubiquinone

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 A Long-Term Extension Study of RP103-MITO-001 (NCT02023866) to Assess RP103 in Children With Inherited Mitochondrial Disease Completed NCT02473445 Phase 2 Cysteamine Bitartrate Delayed-release Capsules
2 MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis Recruiting NCT02171104 Phase 2 IMD Preparative Regimen;Osteopetrosis Only Preparative Regimen;Osteopetrosis Haploidentical Only Preparative Regimen;cALD SR-A (Standard-Risk, Regimen A);cALD SR-B (Standard-Risk, Regimen B);cALD HR-D (High-Risk, Regimen C);cALD HR-D (High-Risk, Regimen D)
3 MNGIE Allogeneic Hematopoietic Stem Cell Transplant Safety Study Recruiting NCT02427178 Phase 1
4 The Natural History Study of Mitochondrial NeuroGastroIntestinal Encephalopathy (MNGIE) Recruiting NCT01694953
5 North American Mitochondrial Disease Consortium Patient Registry and Biorepository (NAMDC) Recruiting NCT01694940
6 Tissue Sample Study for Mitochondrial Disorders Enrolling by invitation NCT01803906

Search NIH Clinical Center for Mitochondrial Dna Depletion Syndrome 1

Genetic Tests for Mitochondrial Dna Depletion Syndrome 1

Genetic tests related to Mitochondrial Dna Depletion Syndrome 1:

# Genetic test Affiliating Genes
1 Mitochondrial Dna Depletion Syndrome 1 (mngie Type) 28 POLG TYMP

Anatomical Context for Mitochondrial Dna Depletion Syndrome 1

Publications for Mitochondrial Dna Depletion Syndrome 1

Articles related to Mitochondrial Dna Depletion Syndrome 1:

# Title Authors Year
1
Polyneuropathy, ophthalmoplegia, leukoencephalopathy, and intestinal pseudo-obstruction: POLIP syndrome. ( 2173474 )
1990

Variations for Mitochondrial Dna Depletion Syndrome 1

UniProtKB/Swiss-Prot genetic disease variations for Mitochondrial Dna Depletion Syndrome 1:

71
# Symbol AA change Variation ID SNP ID
1 TYMP p.Gly145Arg VAR_007643 rs121913037
2 TYMP p.Gly153Ser VAR_007644 rs121913038
3 TYMP p.Lys222Arg VAR_007645 rs149977726
4 TYMP p.Glu289Ala VAR_007646 rs121913036
5 TYMP p.Arg44Gln VAR_016777 rs28931613

ClinVar genetic disease variations for Mitochondrial Dna Depletion Syndrome 1:

6 (show top 50) (show all 79)
# Gene Variation Type Significance SNP ID Assembly Location
1 MT-TK m.8313G> A single nucleotide variant Pathogenic rs118192101 GRCh37 Chromosome MT, 8313: 8313
2 POLG NM_002693.2(POLG): c.1399G> A (p.Ala467Thr) single nucleotide variant Pathogenic/Likely pathogenic rs113994095 GRCh37 Chromosome 15, 89870432: 89870432
3 POLG NM_002693.2(POLG): c.2542G> A (p.Gly848Ser) single nucleotide variant Pathogenic rs113994098 GRCh37 Chromosome 15, 89865023: 89865023
4 TYMP NM_001953.3(TYMP): c.866A> C single nucleotide variant Pathogenic rs121913036 GRCh37 Chromosome 22, 50965067: 50965067
5 TYMP NM_001257988.1(TYMP): c.418_516del single nucleotide variant Pathogenic rs797044454 GRCh38 Chromosome 22, 50528510: 50528510
6 TYMP NM_001113755.2(TYMP): c.433G> A (p.Gly145Arg) single nucleotide variant Pathogenic rs121913037 GRCh37 Chromosome 22, 50967024: 50967024
7 TYMP NM_001953.3(TYMP): c.665A> G single nucleotide variant Pathogenic/Likely pathogenic rs149977726 GRCh37 Chromosome 22, 50965694: 50965694
8 TYMP NM_001257988.1(TYMP): c.1410dupC (p.Ser471Leufs) duplication Pathogenic rs786205097 GRCh37 Chromosome 22, 50964238: 50964238
9 TYMP NM_001953.4(TYMP): c.1160_1300del single nucleotide variant Pathogenic rs797044455 GRCh37 Chromosome 22, 50964571: 50964571
10 TYMP NM_001257988.1(TYMP): c.1193_1198delCGCTGG (p.Ala398_Leu399del) deletion Pathogenic rs786205098 GRCh37 Chromosome 22, 50964532: 50964537
11 TYMP NM_001113755.2(TYMP): c.457G> A (p.Gly153Ser) single nucleotide variant Pathogenic rs121913038 GRCh37 Chromosome 22, 50967000: 50967000
12 TYMP NM_001113755.2(TYMP): c.131G> A (p.Arg44Gln) single nucleotide variant Pathogenic rs28931613 GRCh37 Chromosome 22, 50968008: 50968008
13 TYMP NM_001953.4(TYMP): c.215_417del single nucleotide variant Pathogenic rs767245071 GRCh37 Chromosome 22, 50967768: 50967768
14 TYMP NM_001953.4(TYMP): c.622G> A (p.Val208Met) single nucleotide variant Pathogenic/Likely pathogenic rs121913039 GRCh37 Chromosome 22, 50966041: 50966041
15 TYMP NM_001113755.2(TYMP): c.931G> C (p.Gly311Arg) single nucleotide variant Pathogenic rs121913040 GRCh37 Chromosome 22, 50964903: 50964903
16 TYMP NM_001113755.2(TYMP): c.605G> C (p.Arg202Thr) single nucleotide variant Pathogenic rs121913041 GRCh37 Chromosome 22, 50966058: 50966058
17 TYMP NM_001113755.2(TYMP): c.854T> C (p.Leu285Pro) single nucleotide variant Pathogenic rs121913042 GRCh37 Chromosome 22, 50965079: 50965079
18 TYMP NM_001257989.1(TYMP): c.112G> T (p.Glu38Ter) single nucleotide variant Pathogenic rs1054084896 GRCh38 Chromosome 22, 50529598: 50529598
19 TYMP NM_001257989.1(TYMP): c.128A> C (p.Lys43Thr) single nucleotide variant Pathogenic rs752137335 GRCh38 Chromosome 22, 50529582: 50529582
20 TYMP NM_001257989.1(TYMP): c.146T> G (p.Leu49Arg) single nucleotide variant Pathogenic rs1064792857 GRCh38 Chromosome 22, 50529564: 50529564
21 TYMP NM_001257989.1(TYMP): c.162C> G (p.Ile54Met) single nucleotide variant Pathogenic rs1064792858 GRCh37 Chromosome 22, 50967977: 50967977
22 TYMP NM_001257989.1(TYMP): c.228G> A (p.Met76Ile) single nucleotide variant Pathogenic rs1064792859 GRCh37 Chromosome 22, 50967754: 50967754
23 TYMP NM_001257989.1(TYMP): c.261G> C (p.Glu87Asp) single nucleotide variant Pathogenic rs749827433 GRCh38 Chromosome 22, 50529292: 50529292
24 TYMP NM_001257989.1(TYMP): c.261G> T (p.Glu87Asp) single nucleotide variant Pathogenic rs749827433 GRCh38 Chromosome 22, 50529292: 50529292
25 TYMP NM_001257989.1(TYMP): c.275C> A (p.Thr92Asn) single nucleotide variant Pathogenic rs891107196 GRCh37 Chromosome 22, 50967707: 50967707
26 TYMP NM_001257989.1(TYMP): c.328C> T (p.Gln110Ter) single nucleotide variant Pathogenic rs1064792860 GRCh37 Chromosome 22, 50967654: 50967654
27 TYMP NM_001257989.1(TYMP): c.340G> A (p.Asp114Asn) single nucleotide variant Pathogenic rs1064792861 GRCh38 Chromosome 22, 50529213: 50529213
28 TYMP NM_001257989.1(TYMP): c.398T> C (p.Leu133Pro) single nucleotide variant Pathogenic rs1064792862 GRCh38 Chromosome 22, 50529155: 50529155
29 TYMP NM_001257989.1(TYMP): c.401C> A (p.Ala134Glu) single nucleotide variant Pathogenic rs199901350 GRCh38 Chromosome 22, 50529152: 50529152
30 TYMP NM_001257988.1(TYMP): c.467A> G (p.Asp156Gly) single nucleotide variant Pathogenic rs1064792863 GRCh38 Chromosome 22, 50528561: 50528561
31 TYMP NM_001257989.1(TYMP): c.478T> C (p.Ser160Pro) single nucleotide variant Pathogenic rs1064792864 GRCh38 Chromosome 22, 50528550: 50528550
32 TYMP NM_001257988.1(TYMP): c.518T> G (p.Met173Arg) single nucleotide variant Pathogenic rs1064792865 GRCh38 Chromosome 22, 50527716: 50527716
33 TYMP NM_001257989.1(TYMP): c.530T> C (p.Leu177Pro) single nucleotide variant Pathogenic rs1064792866 GRCh37 Chromosome 22, 50966133: 50966133
34 TYMP NM_001257989.1(TYMP): c.605G> A (p.Arg202Lys) single nucleotide variant Pathogenic rs121913041 GRCh38 Chromosome 22, 50527629: 50527629
35 TYMP NM_001257989.1(TYMP): c.623T> G (p.Val208Gly) single nucleotide variant Pathogenic rs1064792867 GRCh37 Chromosome 22, 50966040: 50966040
36 TYMP NM_001257988.1(TYMP): c.707T> C (p.Phe236Ser) single nucleotide variant Pathogenic rs1064792868 GRCh37 Chromosome 22, 50965652: 50965652
37 TYMP NM_001257989.1(TYMP): c.715G> A (p.Ala239Thr) single nucleotide variant Pathogenic rs1064792869 GRCh37 Chromosome 22, 50965644: 50965644
38 TYMP NM_001257988.1(TYMP): c.760A> C (p.Thr254Pro) single nucleotide variant Pathogenic rs1064792870 GRCh38 Chromosome 22, 50527170: 50527170
39 TYMP NM_001257989.1(TYMP): c.847C> G (p.His283Asp) single nucleotide variant Pathogenic rs1064792871 GRCh37 Chromosome 22, 50965086: 50965086
40 TYMP NM_001257988.1(TYMP): c.856G> A (p.Glu286Lys) single nucleotide variant Pathogenic rs866001342 GRCh37 Chromosome 22, 50965077: 50965077
41 TYMP NM_001257989.1(TYMP): c.865G> A (p.Glu289Lys) single nucleotide variant Pathogenic rs946234163 GRCh37 Chromosome 22, 50965068: 50965068
42 TYMP NM_001257988.1(TYMP): c.893G> A (p.Gly298Asp) single nucleotide variant Pathogenic rs1064792872 GRCh37 Chromosome 22, 50965040: 50965040
43 TYMP NM_001257988.1(TYMP): c.931G> A (p.Gly311Ser) single nucleotide variant Pathogenic rs121913040 GRCh38 Chromosome 22, 50526474: 50526474
44 TYMP NM_001257988.1(TYMP): c.931G> T (p.Gly311Cys) single nucleotide variant Pathogenic rs121913040 GRCh37 Chromosome 22, 50964903: 50964903
45 TYMP NM_001257989.1(TYMP): c.938T> C (p.Leu313Pro) single nucleotide variant Pathogenic rs892141220 GRCh38 Chromosome 22, 50526467: 50526467
46 TYMP NM_001257989.1(TYMP): c.1067T> C (p.Leu356Pro) single nucleotide variant Pathogenic rs1060499532 GRCh37 Chromosome 22, 50964767: 50964767
47 TYMP NM_001257988.1(TYMP): c.1112T> C (p.Leu371Pro) single nucleotide variant Pathogenic rs1060499533 GRCh37 Chromosome 22, 50964722: 50964722
48 TYMP NM_001257988.1(TYMP): c.1159G> A (p.Gly387Ser) single nucleotide variant Pathogenic rs1060499534 GRCh38 Chromosome 22, 50526246: 50526246
49 TYMP NM_001257989.1(TYMP): c.1175G> A (p.Gly392Asp) single nucleotide variant Pathogenic rs1064792873 GRCh37 Chromosome 22, 50964570: 50964570
50 TYMP NM_001257989.1(TYMP): c.1297G> A (p.Gly433Ser) single nucleotide variant Pathogenic rs1064792874 GRCh38 Chromosome 22, 50526019: 50526019

Expression for Mitochondrial Dna Depletion Syndrome 1

Search GEO for disease gene expression data for Mitochondrial Dna Depletion Syndrome 1.

Pathways for Mitochondrial Dna Depletion Syndrome 1

GO Terms for Mitochondrial Dna Depletion Syndrome 1

Sources for Mitochondrial Dna Depletion Syndrome 1

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