MCID: MTC058
MIFTS: 29

Mitochondrial Dna Depletion Syndrome 6

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

Aliases & Classifications for Mitochondrial Dna Depletion Syndrome 6

MalaCards integrated aliases for Mitochondrial Dna Depletion Syndrome 6:

Name: Mitochondrial Dna Depletion Syndrome 6 53 12 71 13 14
Navajo Neurohepatopathy 53 55 71 28 69
Navajo Neuropathy 53 55 71
Navajo Familial Neurogenic Arthropathy 71 69
Mtdps6 53 71
Nnh 53 71
Nn 53 71
Mitochondrial Dna Depletion 6 Hepatocerebral Type 71
Navajo Neurohepatopathy; Nnh 53
Navajo Neuropathy; Nn 53

Characteristics:

Orphanet epidemiological data:

55
navajo neurohepatopathy
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

OMIM:

53
Inheritance:
autosomal recessive

Miscellaneous:
progressive disorder
phenotypic variability
early onset (1 month to 4 years)
frequently occurs in navajo children, especially in western reservations
death in the first decade, usually from liver failure
liver disease may be the most predominant finding


HPO:

31
mitochondrial dna depletion syndrome 6:
Onset and clinical course phenotypic variability infantile onset progressive
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Mitochondrial Dna Depletion Syndrome 6

OMIM : 53 Mitochondrial DNA depletion syndrome-6 is an autosomal recessive disorder characterized by infantile onset of progressive liver failure, often leading to death in the first year of life. Those that survive develop progressive neurologic involvement, including ataxia, hypotonia, dystonia, and psychomotor regression (Spinazzola et al., 2008). For a discussion of genetic heterogeneity of autosomal recessive mtDNA depletion syndromes, see MTDPS1 (603041). (256810)

MalaCards based summary : Mitochondrial Dna Depletion Syndrome 6, also known as navajo neurohepatopathy, is related to mpv17-related hepatocerebral mitochondrial dna depletion syndrome and autoinflammation, lipodystrophy, and dermatosis syndrome, and has symptoms including ataxia, vomiting and diarrhea. An important gene associated with Mitochondrial Dna Depletion Syndrome 6 is MPV17 (MPV17, Mitochondrial Inner Membrane Protein). Affiliated tissues include liver and brain.

UniProtKB/Swiss-Prot : 71 Mitochondrial DNA depletion syndrome 6: A disease due to mitochondrial dysfunction. It is characterized by infantile onset of progressive liver failure, often leading to death in the first year of life, peripheral neuropathy, corneal scarring, acral ulceration and osteomyelitis leading to autoamputation, cerebral leukoencephalopathy, failure to thrive, and recurrent metabolic acidosis with intercurrent infections.

Related Diseases for Mitochondrial Dna Depletion Syndrome 6

Diseases related to Mitochondrial Dna Depletion Syndrome 6 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 mpv17-related hepatocerebral mitochondrial dna depletion syndrome 11.4
2 autoinflammation, lipodystrophy, and dermatosis syndrome 11.1

Symptoms & Phenotypes for Mitochondrial Dna Depletion Syndrome 6

Symptoms via clinical synopsis from OMIM:

53
Neurologic Central Nervous System:
ataxia
dystonia
developmental delay
hypotonia
progressive white matter lesions in the brain

Head And Neck Eyes:
nystagmus
corneal ulcerations

Abdomen Liver:
hepatomegaly
cirrhosis
cholestasis
acute hepatic failure
microvesicular steatosis
more
Metabolic Features:
hypoglycemia
lactic acidosis

Laboratory Abnormalities:
elevated liver enzymes
increased total and conjugated bilirubin

Growth Weight:
poor weight gain

Skeletal Feet:
acral ulceration and osteomyelitis leading to autoamputation

Immunology:
systemic infections

Abdomen Gastroin testinal:
vomiting
diarrhea

Growth Other:
failure to thrive

Growth Height:
short stature

Neurologic Peripheral Nervous System:
areflexia
hyporeflexia
pain insensitivity
muscle weakness, distal
progressive sensorimotor neuropathy
more
Skeletal:
painless fractures due to injury

Skeletal Hands:
acral ulceration and osteomyelitis leading to autoamputation

Skin Nails Hair Skin:
neonatal jaundice


Clinical features from OMIM:

256810

Human phenotypes related to Mitochondrial Dna Depletion Syndrome 6:

31 (show all 32)
# Description HPO Frequency HPO Source Accession
1 ataxia 31 HP:0001251
2 vomiting 31 HP:0002013
3 diarrhea 31 HP:0002014
4 dystonia 31 HP:0001332
5 nystagmus 31 HP:0000639
6 failure to thrive 31 HP:0001508
7 global developmental delay 31 HP:0001263
8 hepatomegaly 31 HP:0002240
9 short stature 31 HP:0004322
10 hypoglycemia 31 HP:0001943
11 elevated hepatic transaminases 31 HP:0002910
12 cirrhosis 31 HP:0001394
13 abnormality of the foot 31 HP:0001760
14 lactic acidosis 31 HP:0003128
15 abnormality of the immune system 31 HP:0002715
16 areflexia 31 HP:0001284
17 acute hepatic failure 31 HP:0006554
18 hyporeflexia 31 HP:0001265
19 prolonged neonatal jaundice 31 HP:0006579
20 sensorimotor neuropathy 31 HP:0007141
21 distal muscle weakness 31 HP:0002460
22 generalized hypotonia 31 HP:0001290
23 increased susceptibility to fractures 31 HP:0002659
24 decreased number of peripheral myelinated nerve fibers 31 HP:0003380
25 pain insensitivity 31 HP:0007021
26 microvesicular hepatic steatosis 31 HP:0001414
27 macrovesicular hepatic steatosis 31 HP:0001403
28 recurrent corneal erosions 31 HP:0000495
29 osteomyelitis leading to amputation due to slow healing fractures 31 HP:0005010
30 painless fractures due to injury 31 HP:0002661
31 reye syndrome-like episodes 31 HP:0006582
32 acral ulceration and osteomyelitis leading to autoamputation of digits 31 HP:0001226

UMLS symptoms related to Mitochondrial Dna Depletion Syndrome 6:


vomiting, diarrhea, ataxia

Drugs & Therapeutics for Mitochondrial Dna Depletion Syndrome 6

Search Clinical Trials , NIH Clinical Center for Mitochondrial Dna Depletion Syndrome 6

Genetic Tests for Mitochondrial Dna Depletion Syndrome 6

Genetic tests related to Mitochondrial Dna Depletion Syndrome 6:

# Genetic test Affiliating Genes
1 Navajo Neurohepatopathy 28 MPV17

Anatomical Context for Mitochondrial Dna Depletion Syndrome 6

MalaCards organs/tissues related to Mitochondrial Dna Depletion Syndrome 6:

38
Liver, Brain

Publications for Mitochondrial Dna Depletion Syndrome 6

Articles related to Mitochondrial Dna Depletion Syndrome 6:

# Title Authors Year
1
Navajo neurohepatopathy is caused by a mutation in the MPV17 gene. ( 16909392 )
2006
2
Navajo neurohepatopathy: a mitochondrial DNA depletion syndrome? ( 11431741 )
2001

Variations for Mitochondrial Dna Depletion Syndrome 6

UniProtKB/Swiss-Prot genetic disease variations for Mitochondrial Dna Depletion Syndrome 6:

71
# Symbol AA change Variation ID SNP ID
1 MPV17 p.Arg50Gln VAR_026217 rs121909721
2 MPV17 p.Arg50Trp VAR_026218 rs121909723
3 MPV17 p.Asn166Lys VAR_026219 rs121909722
4 MPV17 p.Lys88Glu VAR_076199 rs267607256
5 MPV17 p.Gly94Arg VAR_076202 rs267607257
6 MPV17 p.Pro98Leu VAR_076203 rs267607258
7 MPV17 p.Ala162Asp VAR_076204 rs267607259

ClinVar genetic disease variations for Mitochondrial Dna Depletion Syndrome 6:

6 (show all 23)
# Gene Variation Type Significance SNP ID Assembly Location
1 MPV17 NM_002437.4(MPV17): c.149G> A (p.Arg50Gln) single nucleotide variant Pathogenic rs121909721 GRCh37 Chromosome 2, 27535898: 27535898
2 MPV17 NM_002437.4(MPV17): c.498C> A (p.Asn166Lys) single nucleotide variant Pathogenic rs121909722 GRCh37 Chromosome 2, 27532813: 27532813
3 MPV17 NM_002437.4(MPV17): c.148C> T (p.Arg50Trp) single nucleotide variant Pathogenic rs121909723 GRCh37 Chromosome 2, 27535899: 27535899
4 MPV17 MPV17, 26-BP DEL, NT116 deletion Pathogenic
5 MPV17 NM_002437.4(MPV17): c.359G> A (p.Trp120Ter) single nucleotide variant Pathogenic rs121909724 GRCh37 Chromosome 2, 27535377: 27535377
6 MPV17 NM_002437.4(MPV17): c.70G> T (p.Gly24Trp) single nucleotide variant Pathogenic rs121909725 GRCh37 Chromosome 2, 27545315: 27545315
7 MPV17 NM_002437.4(MPV17): c.462-904_*601del1575insGCCTG indel Pathogenic GRCh37 Chromosome 2, 27532179: 27533753
8 MPV17 NM_002437.4(MPV17): c.116_141del26 (p.Arg41Profs) deletion Pathogenic rs397507438 GRCh37 Chromosome 2, 27535906: 27535931
9 MPV17 NM_002437.4(MPV17): c.186+2T> C single nucleotide variant Pathogenic rs147952488 GRCh37 Chromosome 2, 27535859: 27535859
10 MPV17 NM_002437.4(MPV17): c.206G> A (p.Trp69Ter) single nucleotide variant Pathogenic rs267607261 GRCh37 Chromosome 2, 27535620: 27535620
11 MPV17 NM_002437.4(MPV17): c.22_23insC (p.Gln8Profs) insertion Pathogenic rs267607266 GRCh37 Chromosome 2, 27545363: 27545363
12 MPV17 NM_002437.4(MPV17): c.234_242delTGGCACCAC (p.Gly79_Thr81del) deletion Pathogenic rs267607262 GRCh37 Chromosome 2, 27535584: 27535592
13 MPV17 NM_002437.4(MPV17): c.262A> G (p.Lys88Glu) single nucleotide variant Pathogenic rs267607256 GRCh37 Chromosome 2, 27535564: 27535564
14 MPV17 NM_002437.4(MPV17): c.263_265delAGA (p.Lys88del) deletion Pathogenic/Likely pathogenic rs267607263 GRCh37 Chromosome 2, 27535561: 27535563
15 MPV17 NM_002437.4(MPV17): c.271_273delTTG (p.Leu91del) deletion Pathogenic rs267607264 GRCh37 Chromosome 2, 27535553: 27535555
16 MPV17 NM_002437.4(MPV17): c.280G> C (p.Gly94Arg) single nucleotide variant Pathogenic rs267607257 GRCh37 Chromosome 2, 27535456: 27535456
17 MPV17 NM_002437.4(MPV17): c.293C> T (p.Pro98Leu) single nucleotide variant Pathogenic rs267607258 GRCh37 Chromosome 2, 27535443: 27535443
18 MPV17 NM_002437.4(MPV17): c.485C> A (p.Ala162Asp) single nucleotide variant Pathogenic rs267607259 GRCh37 Chromosome 2, 27532826: 27532826
19 MPV17 NM_002437.4(MPV17): c.509C> T (p.Ser170Phe) single nucleotide variant Pathogenic rs267607260 GRCh37 Chromosome 2, 27532802: 27532802
20 MPV17 NM_002437.4(MPV17): c.70+5G> A single nucleotide variant Pathogenic rs267607268 GRCh37 Chromosome 2, 27545310: 27545310
21 MPV17 NM_002437.4(MPV17): c.106C> T (p.Gln36Ter) single nucleotide variant Pathogenic rs754051090 GRCh37 Chromosome 2, 27535941: 27535941
22 MPV17 NM_002437.4(MPV17): c.409-1G> C single nucleotide variant Pathogenic rs886044280 GRCh37 Chromosome 2, 27534820: 27534820
23 MPV17 NM_002437.4(MPV17): c.284dupG (p.Phe96Leufs) duplication Pathogenic rs766160589 GRCh37 Chromosome 2, 27535452: 27535452

Expression for Mitochondrial Dna Depletion Syndrome 6

Search GEO for disease gene expression data for Mitochondrial Dna Depletion Syndrome 6.

Pathways for Mitochondrial Dna Depletion Syndrome 6

GO Terms for Mitochondrial Dna Depletion Syndrome 6

Sources for Mitochondrial Dna Depletion Syndrome 6

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70 UMLS via Orphanet
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