MC5DN5
MCID: MTC141
MIFTS: 36

Mitochondrial Complex V Deficiency, Nuclear Type 5 (MC5DN5)

Categories: Eye diseases, Genetic diseases, Metabolic diseases, Neuronal diseases, Rare diseases, Respiratory diseases

Aliases & Classifications for Mitochondrial Complex V Deficiency, Nuclear Type 5

MalaCards integrated aliases for Mitochondrial Complex V Deficiency, Nuclear Type 5:

Name: Mitochondrial Complex V Deficiency, Nuclear Type 5 57
Mitochondrial Complex V Deficiency 57 12 15
Mitochondrial Complex 5 Deficiency Nuclear Type 5 29 6
Mitochondrial Complex V Deficiency, Atp5f1d Type 57 72
Mitochondrial Complex V Deficiency 20 43
Atp Synthase Deficiency 43 36
Mc5dn5 57 72
Complex 5 Mitochondrial Respiratory Chain Deficiency 20
Mitochondrial Complex V Deficiency, Nuclear Type 5 72
Complex V Deficiency 70

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy or childhood
variable manifestations
two unrelated patients have been reported (last curated september 2018)


HPO:

31
mitochondrial complex v deficiency, nuclear type 5:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Mitochondrial Complex V Deficiency, Nuclear Type 5

MedlinePlus Genetics : 43 Mitochondrial complex V deficiency is a shortage (deficiency) of a protein complex called complex V or a loss of its function. Complex V is found in cell structures called mitochondria, which convert the energy from food into a form that cells can use. Complex V is the last of five mitochondrial complexes that carry out a multistep process called oxidative phosphorylation, through which cells derive much of their energy.Mitochondrial complex V deficiency can cause a wide variety of signs and symptoms affecting many organs and systems of the body, particularly the nervous system and the heart. The disorder can be life-threatening in infancy or early childhood. Affected individuals may have feeding problems, slow growth, low muscle tone (hypotonia), extreme fatigue (lethargy), and developmental delay. They tend to develop elevated levels of lactic acid in the blood (lactic acidosis), which can cause nausea, vomiting, weakness, and rapid breathing. High levels of ammonia in the blood (hyperammonemia) can also occur in affected individuals, and in some cases result in abnormal brain function (encephalopathy) and damage to other organs.Another common feature of mitochondrial complex V deficiency is hypertrophic cardiomyopathy. This condition is characterized by thickening (hypertrophy) of the heart (cardiac) muscle that can lead to heart failure. People with mitochondrial complex V deficiency may also have a characteristic pattern of facial features, including a high forehead, curved eyebrows, outside corners of the eyes that point downward (downslanting palpebral fissures), a prominent bridge of the nose, low-set ears, thin lips, and a small chin (micrognathia).Some people with mitochondrial complex V deficiency have groups of signs and symptoms that are classified as a specific syndrome. For example, mitochondrial complex V deficiency can cause a condition called neuropathy, ataxia, and retinitis pigmentosa (NARP). NARP causes a variety of signs and symptoms chiefly affecting the nervous system. Beginning in childhood or early adulthood, most people with NARP experience numbness, tingling, or pain in the arms and legs (sensory neuropathy); muscle weakness; and problems with balance and coordination (ataxia). Many affected individuals also have cognitive impairment and an eye disorder called retinitis pigmentosa that causes vision loss.A condition called Leigh syndrome can also be caused by mitochondrial complex V deficiency. Leigh syndrome is characterized by progressive loss of mental and movement abilities (developmental or psychomotor regression) and typically results in death within 2 to 3 years after the onset of symptoms. Both NARP and Leigh syndrome can also have other causes.

MalaCards based summary : Mitochondrial Complex V Deficiency, Nuclear Type 5, also known as mitochondrial complex v deficiency, is related to sengers syndrome and isolated atp synthase deficiency. An important gene associated with Mitochondrial Complex V Deficiency, Nuclear Type 5 is ATP5F1D (ATP Synthase F1 Subunit Delta), and among its related pathways/superpathways are Oxidative phosphorylation and Prion disease. Affiliated tissues include heart, eye and liver, and related phenotypes are muscle weakness and global developmental delay

Disease Ontology : 12 A mitochondrial metabolism disease characterized by impaired function of one or more of the proteins making up the mitochondrial proton-transporting ATP synthase complex.

KEGG : 36 ATP synthase deficiency is mitochondrial disease caused by inborn defects in the mitochondrial F1Fo-ATP synthase (respiratory chain complex V). Many patients die within a few months or years. It have been shown to result from mutations in mtDNA genes for the subunits ATP6 and ATP8 or in nuclear genes encoding the biogenesis factors ATPAF2 and TMEM70. Recently, mutations has been found in a nuclear encoded structural complex V subunit, ATP5E and ATP5A1.

UniProtKB/Swiss-Prot : 72 Mitochondrial complex V deficiency, nuclear type 5: A mitochondrial disorder characterized by childhood onset of episodic metabolic decompensation featuring lactic acidosis and hyperammonemia accompanied by ketoacidosis or hypoglycemia. Chronic manifestations include developmental delay, easy fatiguability, and 3- methylglutaconic aciduria. The transmission pattern of MC5DN5 is consistent with autosomal recessive inheritance.

More information from OMIM: 618120 PS604273

Related Diseases for Mitochondrial Complex V Deficiency, Nuclear Type 5

Graphical network of the top 20 diseases related to Mitochondrial Complex V Deficiency, Nuclear Type 5:



Diseases related to Mitochondrial Complex V   Deficiency, Nuclear Type 5

Symptoms & Phenotypes for Mitochondrial Complex V Deficiency, Nuclear Type 5

Human phenotypes related to Mitochondrial Complex V Deficiency, Nuclear Type 5:

31 (show all 17)
# Description HPO Frequency HPO Source Accession
1 muscle weakness 31 HP:0001324
2 global developmental delay 31 HP:0001263
3 delayed speech and language development 31 HP:0000750
4 short stature 31 HP:0004322
5 hypoglycemia 31 HP:0001943
6 elevated serum creatine kinase 31 HP:0003236
7 dilated cardiomyopathy 31 HP:0001644
8 gait imbalance 31 HP:0002141
9 hyperammonemia 31 HP:0001987
10 lethargy 31 HP:0001254
11 encephalopathy 31 HP:0001298
12 lactic acidosis 31 HP:0003128
13 ketoacidosis 31 HP:0001993
14 3-methylglutaconic aciduria 31 HP:0003535
15 exercise intolerance 31 HP:0003546
16 rhabdomyolysis 31 HP:0003201
17 seizure 31 HP:0001250

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Metabolic Features:
hypoglycemia
hyperammonemia
lactic acidosis
ketoacidosis
metabolic decompensation, episodic

Laboratory Abnormalities:
3-methylglutaconic aciduria
mitochondrial complex v deficiency
mitochondria show decreased cristae
increased serum creatine kinase, episodic (patient a)

Growth Height:
short stature (patient a)

Neurologic Central Nervous System:
gait imbalance
lethargy
speech delay
encephalopathy, episodic
delayed development, mild
more
Muscle Soft Tissue:
exercise intolerance
muscle weakness, mild
rhabdomyolysis (patient a)

Cardiovascular Heart:
cardiomyopathy, dilated (patient a)

Clinical features from OMIM®:

618120 (Updated 20-May-2021)

Drugs & Therapeutics for Mitochondrial Complex V Deficiency, Nuclear Type 5

Search Clinical Trials , NIH Clinical Center for Mitochondrial Complex V Deficiency, Nuclear Type 5

Genetic Tests for Mitochondrial Complex V Deficiency, Nuclear Type 5

Genetic tests related to Mitochondrial Complex V Deficiency, Nuclear Type 5:

# Genetic test Affiliating Genes
1 Mitochondrial Complex 5 (atp Synthase) Deficiency Nuclear Type 5 29 ATP5F1D

Anatomical Context for Mitochondrial Complex V Deficiency, Nuclear Type 5

MalaCards organs/tissues related to Mitochondrial Complex V Deficiency, Nuclear Type 5:

40
Heart, Eye, Liver

Publications for Mitochondrial Complex V Deficiency, Nuclear Type 5

Articles related to Mitochondrial Complex V Deficiency, Nuclear Type 5:

# Title Authors PMID Year
1
Biallelic Mutations in ATP5F1D, which Encodes a Subunit of ATP Synthase, Cause a Metabolic Disorder. 6 57
29478781 2018
2
A novel homozygous SLC25A1 mutation with impaired mitochondrial complex V: Possible phenotypic expansion. 61
29226520 2018
3
Mitochondrial epileptic encephalopathy, 3-methylglutaconic aciduria and variable complex V deficiency associated with TIMM50 mutations. 61
27573165 2017
4
Mitochondrial Cardiomyopathies. 61
27504452 2016

Variations for Mitochondrial Complex V Deficiency, Nuclear Type 5

ClinVar genetic disease variations for Mitochondrial Complex V Deficiency, Nuclear Type 5:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 ATP5F1D NM_001687.5(ATP5F1D):c.245C>T (p.Pro82Leu) SNV Pathogenic 453296 rs867410737 GRCh37: 19:1242558-1242558
GRCh38: 19:1242559-1242559
2 ATP5F1D NM_001687.5(ATP5F1D):c.317T>G (p.Val106Gly) SNV Pathogenic 489386 rs1555745989 GRCh37: 19:1244117-1244117
GRCh38: 19:1244118-1244118

UniProtKB/Swiss-Prot genetic disease variations for Mitochondrial Complex V Deficiency, Nuclear Type 5:

72
# Symbol AA change Variation ID SNP ID
1 ATP5F1D p.Pro82Leu VAR_081452 rs867410737
2 ATP5F1D p.Val106Gly VAR_081453 rs155574598

Copy number variations for Mitochondrial Complex V Deficiency, Nuclear Type 5 from CNVD:

7
# CNVD ID Chromosome Start End Type Gene Symbol CNVD Disease
1 80936 13 99432319 99437020 Microdeletion ZIC2 ATP synthase deficiency

Expression for Mitochondrial Complex V Deficiency, Nuclear Type 5

Search GEO for disease gene expression data for Mitochondrial Complex V Deficiency, Nuclear Type 5.

Pathways for Mitochondrial Complex V Deficiency, Nuclear Type 5

Pathways related to Mitochondrial Complex V Deficiency, Nuclear Type 5 according to KEGG:

36
# Name Kegg Source Accession
1 Oxidative phosphorylation hsa00190

Pathways related to Mitochondrial Complex V Deficiency, Nuclear Type 5 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.97 TUBB1 ATP5F1E ATP5F1D ATP5F1A
2 10.18 ATP5F1E ATP5F1D ATP5F1A

GO Terms for Mitochondrial Complex V Deficiency, Nuclear Type 5

Cellular components related to Mitochondrial Complex V Deficiency, Nuclear Type 5 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.8 TMEM70 ATP5F1E ATP5F1D ATP5F1A AGK AARS2
2 mitochondrial inner membrane GO:0005743 9.55 TMEM70 ATP5F1E ATP5F1D ATP5F1A AGK
3 mitochondrial matrix GO:0005759 9.54 ATP5F1E ATP5F1D ATP5F1A
4 mitochondrial proton-transporting ATP synthase complex, catalytic core F(1) GO:0000275 9.26 ATP5F1E ATP5F1D
5 mitochondrial proton-transporting ATP synthase complex GO:0005753 9.13 ATP5F1E ATP5F1D ATP5F1A
6 proton-transporting ATP synthase complex, catalytic core F(1) GO:0045261 8.8 ATP5F1E ATP5F1D ATP5F1A

Biological processes related to Mitochondrial Complex V Deficiency, Nuclear Type 5 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ATP biosynthetic process GO:0006754 9.43 ATP5F1E ATP5F1D ATP5F1A
2 cristae formation GO:0042407 9.33 ATP5F1E ATP5F1D ATP5F1A
3 mitochondrial proton-transporting ATP synthase complex assembly GO:0033615 9.32 TMEM70 ATP5F1D
4 ATP synthesis coupled proton transport GO:0015986 9.13 ATP5F1E ATP5F1D ATP5F1A
5 mitochondrial ATP synthesis coupled proton transport GO:0042776 8.8 ATP5F1E ATP5F1D ATP5F1A

Molecular functions related to Mitochondrial Complex V Deficiency, Nuclear Type 5 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ADP binding GO:0043531 9.16 ATP5F1D ATP5F1A
2 ATPase activity GO:0016887 9.13 ATP5F1E ATP5F1D ATP5F1A
3 proton-transporting ATP synthase activity, rotational mechanism GO:0046933 8.8 ATP5F1E ATP5F1D ATP5F1A

Sources for Mitochondrial Complex V Deficiency, Nuclear Type 5

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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