MMLA
MCID: MTC026
MIFTS: 31

Mitochondrial Myopathy with Lactic Acidosis (MMLA)

Categories: Ear diseases, Fetal diseases, Genetic diseases, Metabolic diseases, Muscle diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Mitochondrial Myopathy with Lactic Acidosis

MalaCards integrated aliases for Mitochondrial Myopathy with Lactic Acidosis:

Name: Mitochondrial Myopathy with Lactic Acidosis 57 20 72 36
Mitochondrial Myopathy-Lactic Acidosis-Deafness Syndrome 58 29 6
Mmla 57 72
Metabolic Myopathy Associated with Chronic Lactic Acidemia, Growth Failure, and Nerve Deafness 20
Mitochondrial Myopathy-Lactic Acidosis-Hearing Loss Syndrome 58
Myopathy, Mitochondrial, with Lactic Acidosis 39

Characteristics:

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive

Miscellaneous:
progressive disorder
onset in first year of life
one patient with compound heterozygous pnpla8 mutations has been reported (last curated may 2015)


HPO:

31
mitochondrial myopathy with lactic acidosis:
Inheritance autosomal recessive inheritance
Onset and clinical course infantile onset progressive


Classifications:

Orphanet: 58  
Rare neurological diseases
Rare otorhinolaryngological diseases
Inborn errors of metabolism
Developmental anomalies during embryogenesis


Summaries for Mitochondrial Myopathy with Lactic Acidosis

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 2597 Definition Mitochondrial myopathy-lactic acidosis-deafness is a type of metabolic myopathy described only in two sisters to date, presenting during childhood, and characterized clinically by growth failure, severe muscle weakness, and moderate sensorineural deafness and biochemically by metabolic acidosis, elevated serum pyruvate concentration, hyperalaninemia and hyperalaninuria. There have been no further descriptions in the literature since 1973.

MalaCards based summary : Mitochondrial Myopathy with Lactic Acidosis, also known as mitochondrial myopathy-lactic acidosis-deafness syndrome, is related to branchiootic syndrome 1 and metabolic myopathy. An important gene associated with Mitochondrial Myopathy with Lactic Acidosis is PNPLA8 (Patatin Like Phospholipase Domain Containing 8). Affiliated tissues include skeletal muscle, heart and monocytes, and related phenotypes are sensorineural hearing impairment and myopathy

KEGG : 36 Mitochondrial myopathy with lactic acidosis is an autosomal recessive metabolic myopathy associated with chronic lactic acidemia, growth failure, and nerve deafness. It has been reported that loss of function mutations in PNPLA8 encoding calcium-independent phospholipase A2 gamma cause this disease.

UniProtKB/Swiss-Prot : 72 Mitochondrial myopathy with lactic acidosis: An autosomal recessive disorder characterized by progressive muscle weakness, hypotonia, seizures, poor weight gain, lactic acidosis, and elevated serum pyruvate concentration. Some patients manifest growth failure and moderate neural deafness.

More information from OMIM: 251950

Related Diseases for Mitochondrial Myopathy with Lactic Acidosis

Diseases related to Mitochondrial Myopathy with Lactic Acidosis via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 11)
# Related Disease Score Top Affiliating Genes
1 branchiootic syndrome 1 10.6
2 metabolic myopathy 10.6
3 mitochondrial complex iv deficiency, nuclear type 1 10.5
4 lactic acidosis 10.3
5 myopathy 10.3
6 mitochondrial myopathy 10.3
7 metabolic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration 10.1
8 encephalopathy, progressive, early-onset, with episodic rhabdomyolysis 10.1
9 metabolic acidosis 10.1
10 acute kidney failure 10.1
11 hypotonia 10.1

Graphical network of the top 20 diseases related to Mitochondrial Myopathy with Lactic Acidosis:



Diseases related to Mitochondrial Myopathy with Lactic Acidosis

Symptoms & Phenotypes for Mitochondrial Myopathy with Lactic Acidosis

Human phenotypes related to Mitochondrial Myopathy with Lactic Acidosis:

58 31 (show all 27)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 sensorineural hearing impairment 58 31 hallmark (90%) Very frequent (99-80%) HP:0000407
2 myopathy 58 31 hallmark (90%) Very frequent (99-80%) HP:0003198
3 skeletal muscle atrophy 58 31 hallmark (90%) Very frequent (99-80%) HP:0003202
4 emg abnormality 58 31 hallmark (90%) Very frequent (99-80%) HP:0003457
5 mitochondrial myopathy 58 31 hallmark (90%) Very frequent (99-80%) HP:0003737
6 metabolic acidosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0001942
7 hyperalaninemia 58 31 hallmark (90%) Very frequent (99-80%) HP:0003348
8 vaginal fistula 58 31 hallmark (90%) Very frequent (99-80%) HP:0004320
9 seizure 31 frequent (33%) HP:0001250
10 seizures 58 Frequent (79-30%)
11 spasticity 31 HP:0001257
12 dysarthria 31 HP:0001260
13 muscle weakness 31 HP:0001324
14 fatigue 31 HP:0012378
15 postnatal growth retardation 31 HP:0008897
16 toe walking 31 HP:0040083
17 increased serum lactate 31 HP:0002151
18 dysmetria 31 HP:0001310
19 dystonia 31 HP:0001332
20 lactic acidosis 31 HP:0003128
21 increased serum pyruvate 31 HP:0003542
22 focal impaired awareness seizure 31 HP:0002384
23 hemiparesis 31 HP:0001269
24 generalized hypotonia 31 HP:0001290
25 moderate sensorineural hearing impairment 31 HP:0008504
26 gowers sign 31 HP:0003391
27 episodic vomiting 31 HP:0002572

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
spasticity
dysmetria
dystonia
loss of fine motor skills
complex partial seizures

Laboratory Abnormalities:
increased serum lactate
increased serum pyruvate

Muscle Soft Tissue:
proximal muscle weakness
gowers sign
hypotonia
toe-walking
loss of ambulation
more
Voice:
dysarthria

Metabolic Features:
lactic acidosis

Growth Weight:
thin habitus

Clinical features from OMIM®:

251950 (Updated 05-Apr-2021)

Drugs & Therapeutics for Mitochondrial Myopathy with Lactic Acidosis

Search Clinical Trials , NIH Clinical Center for Mitochondrial Myopathy with Lactic Acidosis

Genetic Tests for Mitochondrial Myopathy with Lactic Acidosis

Genetic tests related to Mitochondrial Myopathy with Lactic Acidosis:

# Genetic test Affiliating Genes
1 Mitochondrial Myopathy-Lactic Acidosis-Deafness Syndrome 29 PNPLA8

Anatomical Context for Mitochondrial Myopathy with Lactic Acidosis

MalaCards organs/tissues related to Mitochondrial Myopathy with Lactic Acidosis:

40
Skeletal Muscle, Heart, Monocytes

Publications for Mitochondrial Myopathy with Lactic Acidosis

Articles related to Mitochondrial Myopathy with Lactic Acidosis:

(show all 26)
# Title Authors PMID Year
1
Loss of function variants in human PNPLA8 encoding calcium-independent phospholipase A2 γ recapitulate the mitochondriopathy of the homologous null mouse. 6 57
25512002 2015
2
Genetic ablation of calcium-independent phospholipase A2{gamma} leads to alterations in hippocampal cardiolipin content and molecular species distribution, mitochondrial degeneration, autophagy, and cognitive dysfunction. 57 6
19840936 2009
3
Mitochondrial myopathy with cardiomyopathy, lactic acidosis and response to prednisone and thiamine. 57
6938188 1980
4
A metabolic myopathy associated with chronic lactic acidemia, growth failure, and nerve deafness. 57
4725145 1973
5
Multimodal Data Fusion in Learning Analytics: A Systematic Review. 61
33266131 2020
6
Transplantation Induces Profound Changes in the Transcriptional Asset of Hematopoietic Stem Cells: Identification of Specific Signatures Using Machine Learning Techniques. 61
32492887 2020
7
A Scalable Architecture for the Dynamic Deployment of Multimodal Learning Analytics Applications in Smart Classrooms. 61
32455699 2020
8
Pseudouridine synthase 1 deficient mice, a model for Mitochondrial Myopathy with Sideroblastic Anemia, exhibit muscle morphology and physiology alterations. 61
27197761 2016
9
Characterization of scale-free properties of human electrocorticography in awake and slow wave sleep States. 61
22701446 2012
10
Continuous venovenous hemodiafiltration for life-threatening mitochondrial myopathy with lactic acidosis and rhabdomyolysis. 61
17722368 2007
11
Bovine natural killer cells restrict the replication of Mycobacterium bovis in bovine macrophages and enhance IL-12 release by infected macrophages. 61
16730232 2007
12
TNF-alpha activates human monocytes for Paracoccidioides brasiliensis killing by an H2O2-dependent mechanism. 61
16772231 2006
13
Development of surrogate markers for oral immunisation against Candida albicans. 61
12531338 2003
14
Nitric oxide-enhanced resistance to oral candidiasis. 61
11899431 2001
15
Effects of opsonization and gamma interferon on growth of Brucella melitensis 16M in mouse peritoneal macrophages in vitro. 61
10603396 2000
16
Regulation of inflammatory responses to Bordetella pertussis by N(G)-monomethyl-L-arginine in mice intranasally infected. 61
10704086 1999
17
Nitric oxide-independent killing of Francisella tularensis by IFN-gamma-stimulated murine alveolar macrophages. 61
8027551 1994
18
[The autoregulation of the coronary flow of the isolated rat heart after NO-synthase blockade]. 61
7509647 1993
19
[Effect of endogenous metabolites on autoregulation and dilational reserve of coronary vessels]. 61
7519066 1993
20
Activation of human macrophages for the killing of intracellular Trypanosoma cruzi by TNF-alpha and IFN-gamma through a nitric oxide-dependent mechanism. 61
1330900 1992
21
Comparison of Methods for Isolation of Listeria from Raw Milk. 61
31051601 1991
22
Efficacy of direct plating media for recovering Listeria monocytogenes from foods. 61
2119210 1990
23
Direct plating technique for enumeration of Listeria monocytogenes in foods. 61
3134335 1988
24
Delayed appearance of blood lactate with reduced frequency breathing during exercise. 61
3135187 1988
25
Mitochondrial myopathy with lactic acidosis and deficient activity of muscle succinate cytochrome-c-oxidoreductase. 61
6096151 1984
26
Mitochondrial cytochrome deficiency presenting as a myopathy with hypotonia, external ophthalmoplegia, and lactic acidosis in an infant and as fatal hepatopathy in a second cousin. 61
6314875 1983

Variations for Mitochondrial Myopathy with Lactic Acidosis

ClinVar genetic disease variations for Mitochondrial Myopathy with Lactic Acidosis:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 PNPLA8 NM_001256007.3(PNPLA8):c.634_637del (p.Asn212fs) Deletion Pathogenic 190127 rs786205882 GRCh37: 7:108155299-108155302
GRCh38: 7:108514855-108514858
2 PNPLA8 NM_001256007.3(PNPLA8):c.2273_2274CT[1] (p.Leu759fs) Microsatellite Pathogenic 190128 rs774184465 GRCh37: 7:108112918-108112919
GRCh38: 7:108472474-108472475
3 PNPLA8 NM_001256007.3(PNPLA8):c.1580G>A (p.Trp527Ter) SNV Likely pathogenic 804406 rs1598909288 GRCh37: 7:108137073-108137073
GRCh38: 7:108496629-108496629
4 PNPLA8 NM_001256007.3(PNPLA8):c.2161G>A (p.Glu721Lys) SNV Uncertain significance 870407 GRCh37: 7:108113033-108113033
GRCh38: 7:108472589-108472589
5 PNPLA8 NM_001256007.3(PNPLA8):c.559C>T (p.Arg187Cys) SNV Uncertain significance 634462 rs139626312 GRCh37: 7:108155377-108155377
GRCh38: 7:108514933-108514933
6 PNPLA8 NM_001256007.3(PNPLA8):c.373C>T (p.Arg125Cys) SNV Uncertain significance 1031939 GRCh37: 7:108155563-108155563
GRCh38: 7:108515119-108515119

Expression for Mitochondrial Myopathy with Lactic Acidosis

Search GEO for disease gene expression data for Mitochondrial Myopathy with Lactic Acidosis.

Pathways for Mitochondrial Myopathy with Lactic Acidosis

GO Terms for Mitochondrial Myopathy with Lactic Acidosis

Sources for Mitochondrial Myopathy with Lactic Acidosis

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
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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 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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