MTDPS3
MCID: MTC063
MIFTS: 32

Mitochondrial Dna Depletion Syndrome 3 (MTDPS3)

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 3

MalaCards integrated aliases for Mitochondrial Dna Depletion Syndrome 3:

Name: Mitochondrial Dna Depletion Syndrome 3 57 12 75 13 6 73
Mitochondrial Dna-Depletion Syndrome 3, Hepatocerebral 29 6
Mtdps3 57 75
Mitochondrial Dna Depletion Syndrome, Hepatocerebral Form Due to Dguok Deficiency 59
Hepatocerebral Mitochondrial Dna Deletions Syndrome Autosomal Recessive 75
Mitochondrial Dna Depletion Syndrome 3 Hepatocerebral Type 75
Mitochondrial Dna Depletion Syndrome , Type 3 40

Characteristics:

Orphanet epidemiological data:

59
mitochondrial dna depletion syndrome, hepatocerebral form due to dguok deficiency
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal; Age of death: early childhood;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
onset as neonate
hepatic failure develops in first months of life
most patients die of hepatic failure by 9 months of age


HPO:

32
mitochondrial dna depletion syndrome 3:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Mitochondrial Dna Depletion Syndrome 3

OMIM : 57 Mitochondrial DNA depletion syndrome-3 is a severe autosomal recessive disorder characterized by onset in infancy of progressive liver failure and neurologic abnormalities, hypoglycemia, and increased lactate in body fluids. Affected tissues show both decreased activity of the mtDNA-encoded respiratory chain complexes (I, III, IV, and V) and mtDNA depletion (Mandel et al., 2001). For a discussion of genetic heterogeneity of autosomal recessive mtDNA depletion syndromes, see MTDPS1 (603041). (251880)

MalaCards based summary : Mitochondrial Dna Depletion Syndrome 3, also known as mitochondrial dna-depletion syndrome 3, hepatocerebral, is related to mitochondrial dna depletion syndrome, hepatocerebral form due to dguok deficiency and mitochondrial dna depletion syndrome, and has symptoms including seizures, vomiting and icterus. An important gene associated with Mitochondrial Dna Depletion Syndrome 3 is DGUOK (Deoxyguanosine Kinase). Affiliated tissues include liver, eye and bone, and related phenotypes are nystagmus and seizures

UniProtKB/Swiss-Prot : 75 Mitochondrial DNA depletion syndrome 3: A disorder due to mitochondrial dysfunction characterized by onset in infancy of progressive liver failure, hypoglycemia, increased lactate in body fluids, and neurologic abnormalities including hypotonia, encephalopathy, peripheral neuropathy. Affected tissues show both decreased activity of the mtDNA-encoded respiratory chain complexes and mtDNA depletion.

Related Diseases for Mitochondrial Dna Depletion Syndrome 3

Symptoms & Phenotypes for Mitochondrial Dna Depletion Syndrome 3

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
nystagmus
disconjugate eye movements
optic dysplasia

Growth Other:
failure to thrive
poor growth

Abdomen Spleen:
splenomegaly

Abdomen External Features:
portal hypertension
ascites

Neurologic Peripheral Nervous System:
peripheral neuropathy

Skin Nails Hair Skin:
jaundice

Head And Neck Head:
microcephaly (less common)

Neurologic Central Nervous System:
nystagmus
seizures
hyperreflexia
encephalopathy
cerebral atrophy
more
Metabolic Features:
hypothermia
hypoglycemia
lactic acidosis

Abdomen Liver:
hepatomegaly
jaundice
cholestasis
hepatic failure
hepatocellular necrosis
more
Abdomen Gastrointestinal:
vomiting
poor feeding

Hematology:
thrombocytopenia
coagulopathy due to hepatic failure

Laboratory Abnormalities:
hyperbilirubinemia
hypoalbuminemia
generalized aminoaciduria
abnormal liver function tests


Clinical features from OMIM:

251880

Human phenotypes related to Mitochondrial Dna Depletion Syndrome 3:

32 (show all 34)
# Description HPO Frequency HPO Source Accession
1 nystagmus 32 HP:0000639
2 seizures 32 HP:0001250
3 muscular hypotonia 32 HP:0001252
4 hyperreflexia 32 HP:0001347
5 failure to thrive 32 HP:0001508
6 hypothermia 32 HP:0002045
7 splenomegaly 32 HP:0001744
8 hepatomegaly 32 HP:0002240
9 microcephaly 32 HP:0000252
10 feeding difficulties in infancy 32 HP:0008872
11 portal hypertension 32 HP:0001409
12 vomiting 32 HP:0002013
13 hypoglycemia 32 HP:0001943
14 ascites 32 HP:0001541
15 growth delay 32 HP:0001510
16 hepatic steatosis 32 HP:0001397
17 thrombocytopenia 32 HP:0001873
18 jaundice 32 HP:0000952
19 lactic acidosis 32 HP:0003128
20 hepatic failure 32 HP:0001399
21 hyperbilirubinemia 32 HP:0002904
22 generalized hypotonia 32 HP:0001290
23 encephalopathy 32 HP:0001298
24 polyneuropathy 32 HP:0001271
25 cerebral atrophy 32 HP:0002059
26 hypoalbuminemia 32 HP:0003073
27 decreased activity of mitochondrial respiratory chain 32 HP:0008972
28 generalized aminoaciduria 32 HP:0002909
29 abnormal conjugate eye movement 32 HP:0000549
30 micronodular cirrhosis 32 HP:0001413
31 hepatocellular necrosis 32 HP:0001404
32 periportal fibrosis 32 HP:0001405
33 elevated hepatic transaminase 32 HP:0002910
34 depletion of mitochondrial dna in liver 32 HP:0006581

UMLS symptoms related to Mitochondrial Dna Depletion Syndrome 3:


seizures, vomiting, icterus

Drugs & Therapeutics for Mitochondrial Dna Depletion Syndrome 3

Search Clinical Trials , NIH Clinical Center for Mitochondrial Dna Depletion Syndrome 3

Genetic Tests for Mitochondrial Dna Depletion Syndrome 3

Genetic tests related to Mitochondrial Dna Depletion Syndrome 3:

# Genetic test Affiliating Genes
1 Mitochondrial Dna-Depletion Syndrome 3, Hepatocerebral 29 DGUOK

Anatomical Context for Mitochondrial Dna Depletion Syndrome 3

MalaCards organs/tissues related to Mitochondrial Dna Depletion Syndrome 3:

41
Liver, Eye, Bone, Testes

Publications for Mitochondrial Dna Depletion Syndrome 3

Variations for Mitochondrial Dna Depletion Syndrome 3

UniProtKB/Swiss-Prot genetic disease variations for Mitochondrial Dna Depletion Syndrome 3:

75
# Symbol AA change Variation ID SNP ID
1 DGUOK p.Arg142Lys VAR_019417 rs104893631
2 DGUOK p.Glu227Lys VAR_019418 rs104893632
3 DGUOK p.Leu250Ser VAR_023789 rs749464475

ClinVar genetic disease variations for Mitochondrial Dna Depletion Syndrome 3:

6 (show all 36)
# Gene Variation Type Significance SNP ID Assembly Location
1 TWNK NM_021830.4(TWNK): c.1370C> T (p.Thr457Ile) single nucleotide variant Pathogenic rs80356544 GRCh37 Chromosome 10, 102749527: 102749527
2 TWNK NM_021830.4(TWNK): c.1370C> T (p.Thr457Ile) single nucleotide variant Pathogenic rs80356544 GRCh38 Chromosome 10, 100989770: 100989770
3 DGUOK NM_080916.2(DGUOK): c.255delA (p.Ala86Profs) deletion Pathogenic rs886037613 GRCh37 Chromosome 2, 74166149: 74166149
4 DGUOK NM_080916.2(DGUOK): c.255delA (p.Ala86Profs) deletion Pathogenic rs886037613 GRCh38 Chromosome 2, 73939022: 73939022
5 DGUOK NM_080916.2(DGUOK): c.313C> T (p.Arg105Ter) single nucleotide variant Pathogenic rs104893630 GRCh37 Chromosome 2, 74173903: 74173903
6 DGUOK NM_080916.2(DGUOK): c.313C> T (p.Arg105Ter) single nucleotide variant Pathogenic rs104893630 GRCh38 Chromosome 2, 73946776: 73946776
7 DGUOK NM_080916.2(DGUOK): c.763_766dupGATT (p.Phe256Terfs) duplication Pathogenic rs886037614 GRCh37 Chromosome 2, 74185328: 74185331
8 DGUOK NM_080916.2(DGUOK): c.763_766dupGATT (p.Phe256Terfs) duplication Pathogenic rs886037614 GRCh38 Chromosome 2, 73958201: 73958204
9 DGUOK NM_080916.2(DGUOK): c.609_610delGT (p.Tyr204Profs) deletion Pathogenic rs886037615 GRCh37 Chromosome 2, 74184269: 74184270
10 DGUOK NM_080916.2(DGUOK): c.609_610delGT (p.Tyr204Profs) deletion Pathogenic rs886037615 GRCh38 Chromosome 2, 73957142: 73957143
11 DGUOK NM_080916.2(DGUOK): c.425G> A (p.Arg142Lys) single nucleotide variant Pathogenic rs104893631 GRCh37 Chromosome 2, 74174015: 74174015
12 DGUOK NM_080916.2(DGUOK): c.425G> A (p.Arg142Lys) single nucleotide variant Pathogenic rs104893631 GRCh38 Chromosome 2, 73946888: 73946888
13 DGUOK NM_080916.2(DGUOK): c.679G> A (p.Glu227Lys) single nucleotide variant Pathogenic rs104893632 GRCh37 Chromosome 2, 74184339: 74184339
14 DGUOK NM_080916.2(DGUOK): c.679G> A (p.Glu227Lys) single nucleotide variant Pathogenic rs104893632 GRCh38 Chromosome 2, 73957212: 73957212
15 DGUOK NM_080916.2(DGUOK): c.763G> T (p.Asp255Tyr) single nucleotide variant Pathogenic rs104893633 GRCh37 Chromosome 2, 74185328: 74185328
16 DGUOK NM_080916.2(DGUOK): c.763G> T (p.Asp255Tyr) single nucleotide variant Pathogenic rs104893633 GRCh38 Chromosome 2, 73958201: 73958201
17 DGUOK NM_080916.2(DGUOK): c.287T> C (p.Leu96Pro) single nucleotide variant Likely pathogenic rs587780587 GRCh37 Chromosome 2, 74173877: 74173877
18 DGUOK NM_080916.2(DGUOK): c.287T> C (p.Leu96Pro) single nucleotide variant Likely pathogenic rs587780587 GRCh38 Chromosome 2, 73946750: 73946750
19 DGUOK NM_080916.2(DGUOK): c.*13A> T single nucleotide variant Benign rs4777 GRCh37 Chromosome 2, 74185876: 74185876
20 DGUOK NM_080916.2(DGUOK): c.*13A> T single nucleotide variant Benign rs4777 GRCh38 Chromosome 2, 73958749: 73958749
21 DGUOK NM_080916.2(DGUOK): c.4G> T (p.Ala2Ser) single nucleotide variant Uncertain significance rs147551003 GRCh37 Chromosome 2, 74154041: 74154041
22 DGUOK NM_080916.2(DGUOK): c.4G> T (p.Ala2Ser) single nucleotide variant Uncertain significance rs147551003 GRCh38 Chromosome 2, 73926914: 73926914
23 DGUOK NM_080916.2(DGUOK): c.605_606delGA (p.Arg202Thrfs) deletion Pathogenic rs863223949 GRCh38 Chromosome 2, 73957138: 73957139
24 DGUOK NM_080916.2(DGUOK): c.605_606delGA (p.Arg202Thrfs) deletion Pathogenic rs863223949 GRCh37 Chromosome 2, 74184265: 74184266
25 DGUOK NM_080916.2(DGUOK): c.137A> G (p.Asn46Ser) single nucleotide variant Pathogenic/Likely pathogenic rs763615602 GRCh37 Chromosome 2, 74154174: 74154174
26 DGUOK NM_080916.2(DGUOK): c.137A> G (p.Asn46Ser) single nucleotide variant Pathogenic/Likely pathogenic rs763615602 GRCh38 Chromosome 2, 73927047: 73927047
27 DGUOK NM_080916.2(DGUOK): c.797T> G (p.Leu266Arg) single nucleotide variant Pathogenic rs886037846 GRCh37 Chromosome 2, 74185362: 74185362
28 DGUOK NM_080916.2(DGUOK): c.797T> G (p.Leu266Arg) single nucleotide variant Pathogenic rs886037846 GRCh38 Chromosome 2, 73958235: 73958235
29 DGUOK NM_080916.2(DGUOK): c.353G> A (p.Arg118His) single nucleotide variant Likely pathogenic rs150678946 GRCh37 Chromosome 2, 74173943: 74173943
30 DGUOK NM_080916.2(DGUOK): c.353G> A (p.Arg118His) single nucleotide variant Likely pathogenic rs150678946 GRCh38 Chromosome 2, 73946816: 73946816
31 DGUOK NM_080916.2(DGUOK): c.443+1G> A single nucleotide variant Pathogenic rs1057524864 GRCh37 Chromosome 2, 74174034: 74174034
32 DGUOK NM_080916.2(DGUOK): c.443+1G> A single nucleotide variant Pathogenic rs1057524864 GRCh38 Chromosome 2, 73946907: 73946907
33 DGUOK NM_080916.2(DGUOK): c.155C> T (p.Ser52Phe) single nucleotide variant Pathogenic GRCh37 Chromosome 2, 74166049: 74166049
34 DGUOK NM_080916.2(DGUOK): c.155C> T (p.Ser52Phe) single nucleotide variant Pathogenic GRCh38 Chromosome 2, 73938922: 73938922
35 DGUOK NM_080916.2(DGUOK): c.749T> C (p.Leu250Ser) single nucleotide variant Pathogenic rs749464475 GRCh37 Chromosome 2, 74185314: 74185314
36 DGUOK NM_080916.2(DGUOK): c.749T> C (p.Leu250Ser) single nucleotide variant Pathogenic rs749464475 GRCh38 Chromosome 2, 73958187: 73958187

Expression for Mitochondrial Dna Depletion Syndrome 3

Search GEO for disease gene expression data for Mitochondrial Dna Depletion Syndrome 3.

Pathways for Mitochondrial Dna Depletion Syndrome 3

GO Terms for Mitochondrial Dna Depletion Syndrome 3

Cellular components related to Mitochondrial Dna Depletion Syndrome 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrial matrix GO:0005759 8.62 DGUOK TWNK

Sources for Mitochondrial Dna Depletion Syndrome 3

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
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69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
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73 UMLS
74 UMLS via Orphanet
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