HML
MCID: MYP097
MIFTS: 31

Myopathy with Lactic Acidosis, Hereditary (HML)

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

Aliases & Classifications for Myopathy with Lactic Acidosis, Hereditary

MalaCards integrated aliases for Myopathy with Lactic Acidosis, Hereditary:

Name: Myopathy with Lactic Acidosis, Hereditary 57 29 13 6 39
Myopathy with Exercise Intolerance, Swedish Type 57 58 70
Myopathy with Deficiency of Succinate Dehydrogenase and Aconitase 57 72
Myoglobinuria Due to Abnormal Glycolysis 57 72
Hml 57 72
Hereditary Myopathy with Lactic Acidosis Due to Iscu Deficiency 58
Myopathy with Exercise Intolerance Swedish Type 72
Hereditary Myopathy with Lactic Acidosis 72
Iron-Sulfur Cluster Deficiency Myopathy 58
Aconitase Deficiency 58
Iscu Myopathy 58
Meis 72

Characteristics:

Orphanet epidemiological data:

58
hereditary myopathy with lactic acidosis due to iscu deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

OMIM®:

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

Miscellaneous:
onset in childhood
chronic course with exacerbations and remissions
low physical performance
early exhaustion on exertion


HPO:

31
myopathy with lactic acidosis, hereditary:
Inheritance autosomal recessive inheritance
Onset and clinical course juvenile onset


Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism


External Ids:

OMIM® 57 255125
ICD10 via Orphanet 33 G71.3
UMLS via Orphanet 71 C1850718
Orphanet 58 ORPHA43115
MedGen 41 C1850718
UMLS 70 C1850718

Summaries for Myopathy with Lactic Acidosis, Hereditary

UniProtKB/Swiss-Prot : 72 Myopathy with exercise intolerance Swedish type: Autosomal recessive metabolic disease characterized by lifelong severe exercise intolerance, in which minor exertion causes fatigue of active muscles, shortness of breath, and cardiac palpitations in association with lactic acidosis. The biochemical phenotype is characterized by a deficiency in mitochondrial iron-sulfur proteins and impaired muscle oxidative metabolism.

MalaCards based summary : Myopathy with Lactic Acidosis, Hereditary, also known as myopathy with exercise intolerance, swedish type, is related to myopathy with deficiency of iscu and myopathy, lactic acidosis, and sideroblastic anemia, and has symptoms including muscle cramp An important gene associated with Myopathy with Lactic Acidosis, Hereditary is ISCU (Iron-Sulfur Cluster Assembly Enzyme). The drug Iron has been mentioned in the context of this disorder. Affiliated tissues include skeletal muscle, and related phenotypes are rhabdomyolysis and muscle weakness

OMIM® : 57 Hereditary myopathy with lactic acidosis is an autosomal recessive muscular disorder characterized by childhood onset of exercise intolerance with muscle tenderness, cramping, dyspnea, and palpitations. Biochemical features include lactic acidosis and, rarely, rhabdomyolysis. It is a chronic disorder with remission and exacerbation of the muscle phenotype (summary by Sanaker et al., 2010). (255125) (Updated 05-Apr-2021)

Related Diseases for Myopathy with Lactic Acidosis, Hereditary

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

(show top 50) (show all 74)
# Related Disease Score Top Affiliating Genes
1 myopathy with deficiency of iscu 11.7
2 myopathy, lactic acidosis, and sideroblastic anemia 11.1
3 myopathy with deficiency of iron-sulfur cluster assembly enzyme 11.0
4 lactic acidosis 10.4
5 myoglobinuria 10.2
6 myopathy 10.2
7 metabolic myopathy 10.2
8 leukemia, acute myeloid 10.2
9 metabolic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration 10.1
10 encephalopathy, progressive, early-onset, with episodic rhabdomyolysis 10.1
11 autosomal recessive disease 10.1
12 amyotrophic lateral sclerosis 1 10.1
13 alpha/beta t-cell lymphopenia with gamma/delta t-cell expansion, severe cytomegalovirus infection, and autoimmunity 10.1
14 lymphoma 10.1
15 lateral sclerosis 10.1
16 neuroblastoma 10.0
17 rheumatoid arthritis 10.0
18 mycosis fungoides 10.0
19 mantle cell lymphoma 10.0
20 lymphoblastic lymphoma 10.0
21 hairy cell leukemia 10.0
22 teratocarcinoma 10.0
23 embryonal carcinoma 10.0
24 germ cells tumors 10.0
25 infantile cerebellar-retinal degeneration 9.9
26 mitochondrial myopathy 9.9
27 retinal degeneration 9.9
28 ovarian cancer 9.9
29 tetralogy of fallot 9.9
30 conotruncal heart malformations 9.9
31 thymoma, familial 9.9
32 leukemia, acute lymphoblastic 9.9
33 helix syndrome 9.9
34 heart disease 9.9
35 leukemia 9.9
36 ventricular septal defect 9.9
37 heart septal defect 9.9
38 glioblastoma 9.9
39 thymoma 9.9
40 phocomelia 9.9
41 precursor t-cell acute lymphoblastic leukemia 9.9
42 burkitt lymphoma 9.8
43 breast cancer 9.8
44 hepatocellular carcinoma 9.8
45 leukemia, chronic lymphocytic 9.8
46 myelopathy, htlv-1-associated 9.8
47 prostate cancer 9.8
48 aging 9.8
49 branchiootic syndrome 1 9.8
50 hepatitis c virus 9.8

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



Diseases related to Myopathy with Lactic Acidosis, Hereditary

Symptoms & Phenotypes for Myopathy with Lactic Acidosis, Hereditary

Human phenotypes related to Myopathy with Lactic Acidosis, Hereditary:

31 (show all 19)
# Description HPO Frequency HPO Source Accession
1 rhabdomyolysis 31 occasional (7.5%) HP:0003201
2 muscle weakness 31 HP:0001324
3 myopathy 31 HP:0003198
4 elevated serum creatine kinase 31 HP:0003236
5 dyspnea 31 HP:0002094
6 increased serum lactate 31 HP:0002151
7 decreased activity of mitochondrial complex i 31 HP:0011923
8 lactic acidosis 31 HP:0003128
9 mitochondrial myopathy 31 HP:0003737
10 muscle spasm 31 HP:0003394
11 increased intramyocellular lipid droplets 31 HP:0012240
12 palpitations 31 HP:0001962
13 exercise intolerance 31 HP:0003546
14 myoglobinuria 31 HP:0002913
15 decreased activity of mitochondrial complex iii 31 HP:0011924
16 decreased activity of mitochondrial complex ii 31 HP:0008314
17 subsarcolemmal accumulations of abnormally shaped mitochondria 31 HP:0003548
18 sideroblastic anemia 31 HP:0001924
19 abnormal iron deposition in mitochondria 31 HP:0008306

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Muscle Soft Tissue:
myopathy
exercise intolerance
abnormal iron deposition in mitochondria
muscle cramps
premature exertional muscle weakness
more
Laboratory Abnormalities:
myoglobinuria
increased serum creatine kinase during episodes
disproportionate work-related increase in blood lactate and pyruvate
low maximal oxygen uptake on exercise testing

Metabolic Features:
lactic acidosis

Clinical features from OMIM®:

255125 (Updated 05-Apr-2021)

UMLS symptoms related to Myopathy with Lactic Acidosis, Hereditary:


muscle cramp

Drugs & Therapeutics for Myopathy with Lactic Acidosis, Hereditary

Drugs for Myopathy with Lactic Acidosis, Hereditary (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Iron Approved 7439-89-6 23925 29936

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Investigations Into ISCU Myopathy or Iron Sulfur Scaffold U Protein Myopathy Completed NCT01547767

Search NIH Clinical Center for Myopathy with Lactic Acidosis, Hereditary

Genetic Tests for Myopathy with Lactic Acidosis, Hereditary

Genetic tests related to Myopathy with Lactic Acidosis, Hereditary:

# Genetic test Affiliating Genes
1 Myopathy with Lactic Acidosis, Hereditary 29 ISCU

Anatomical Context for Myopathy with Lactic Acidosis, Hereditary

MalaCards organs/tissues related to Myopathy with Lactic Acidosis, Hereditary:

40
Skeletal Muscle

Publications for Myopathy with Lactic Acidosis, Hereditary

Articles related to Myopathy with Lactic Acidosis, Hereditary:

(show all 15)
# Title Authors PMID Year
1
Differences in RNA processing underlie the tissue specific phenotype of ISCU myopathy. 6 57 61
20206689 2010
2
Antisense oligonucleotide therapeutics for iron-sulphur cluster deficiency myopathy. 57 6
19846308 2009
3
Clinical manifestation and a new ISCU mutation in iron-sulphur cluster deficiency myopathy. 57 6
19567699 2009
4
Myopathy with lactic acidosis is linked to chromosome 12q23.3-24.11 and caused by an intron mutation in the ISCU gene resulting in a splicing defect. 6 57
18296749 2008
5
Splice mutation in the iron-sulfur cluster scaffold protein ISCU causes myopathy with exercise intolerance. 6 57
18304497 2008
6
The defective splicing caused by the ISCU intron mutation in patients with myopathy with lactic acidosis is repressed by PTBP1 but can be derepressed by IGF2BP1. 6
22125086 2012
7
Tissue-specific splicing of ISCU results in a skeletal muscle phenotype in myopathy with lactic acidosis, while complete loss of ISCU results in early embryonic death in mice. 6
21165651 2011
8
Hereditary myopathy with lactic acidosis, succinate dehydrogenase and aconitase deficiency in northern Sweden: a genealogical study. 57
7616539 1995
9
Mitochondrial myopathy with succinate dehydrogenase and aconitase deficiency. Abnormalities of several iron-sulfur proteins. 57
8254022 1993
10
Deficiency of skeletal muscle succinate dehydrogenase and aconitase. Pathophysiology of exercise in a novel human muscle oxidative defect. 57
1918374 1991
11
Low succinate dehydrogenase (SDH) activity in a patient with a hereditary myopathy with paroxysmal myoglobinuria. 57
2384736 1990
12
Mitochondrial myopathy with a defect of mitochondrial-protein transport. 57
2113185 1990
13
Amino acid metabolism in patients with a hereditary myopathy and paroxysmal myoglobinuria. 57
506803 1979
14
Hereditary abnormal muscle metabolism with hyperkinetic circulation during exercise. 57
5811159 1969
15
HEREDITARY METABOLIC MYOPATHY WITH PAROXYSMAL MYOGLOBINURIA DUE TO ABNORMAL GLYCOLYSIS. 57
14213465 1964

Variations for Myopathy with Lactic Acidosis, Hereditary

ClinVar genetic disease variations for Myopathy with Lactic Acidosis, Hereditary:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 ISCU ISCU, IVS5, G-C, +382 SNV Pathogenic 782 GRCh37:
GRCh38:
2 ISCU NM_014301.4(ISCU):c.343+382G>C SNV Pathogenic 223141 rs767000507 GRCh37: 12:108961426-108961426
GRCh38: 12:108567650-108567650
3 ISCU NM_014301.4(ISCU):c.74G>A (p.Gly25Glu) SNV Pathogenic 783 rs267607190 GRCh37: 12:108958089-108958089
GRCh38: 12:108564313-108564313
4 ISCU NM_213595.4(ISCU):c.338_339+2del Deletion Pathogenic 1033707 GRCh37: 12:108959206-108959209
GRCh38: 12:108565430-108565433

Expression for Myopathy with Lactic Acidosis, Hereditary

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

Pathways for Myopathy with Lactic Acidosis, Hereditary

GO Terms for Myopathy with Lactic Acidosis, Hereditary

Sources for Myopathy with Lactic Acidosis, Hereditary

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