MMDS2
MCID: MLT150
MIFTS: 27

Multiple Mitochondrial Dysfunctions Syndrome 2 with Hyperglycinemia (MMDS2)

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

Aliases & Classifications for Multiple Mitochondrial Dysfunctions Syndrome 2 with...

MalaCards integrated aliases for Multiple Mitochondrial Dysfunctions Syndrome 2 with Hyperglycinemia:

Name: Multiple Mitochondrial Dysfunctions Syndrome 2 with Hyperglycinemia 58 12 76
Multiple Mitochondrial Dysfunctions Syndrome 2 30 13 6 15 74
Mmds2 58 76
Mitochondrial Dysfunctions Syndrome, Multiple, Type 2 41
Multiple Mitochondrial Dysfunctions Syndrome Type 2 60
Bola3 Deficiency 60

Characteristics:

Orphanet epidemiological data:

60
multiple mitochondrial dysfunctions syndrome type 2
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Neonatal;

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy
death in early childhood may occur


HPO:

33
multiple mitochondrial dysfunctions syndrome 2 with hyperglycinemia:
Clinical modifier death in infancy
Onset and clinical course infantile onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Multiple Mitochondrial Dysfunctions Syndrome 2 with...

OMIM : 58 Multiple mitochondrial dysfunctions syndrome-2 (MMDS2) with hyperglycinemia is a severe autosomal recessive disorder characterized by developmental regression in infancy. Affected children have an encephalopathic disease course with seizures, spasticity, loss of head control, and abnormal movement. Additional more variable features include optic atrophy, cardiomyopathy, and leukodystrophy. Laboratory studies show increased serum glycine and lactate. Most patients die in childhood. The disorder represents a form of 'variant' nonketotic hyperglycinemia and is distinct from classic nonketotic hyperglycinemia (NKH, or GCE; 605899), which is characterized by significantly increased CSF glycine. Several forms of 'variant' NKH, including MMDS2, appear to result from defects of mitochondrial lipoate biosynthesis (summary by Baker et al., 2014). For a general description and a discussion of genetic heterogeneity of multiple mitochondrial dysfunctions syndrome, see MMDS1 (605711). (614299)

MalaCards based summary : Multiple Mitochondrial Dysfunctions Syndrome 2 with Hyperglycinemia, also known as multiple mitochondrial dysfunctions syndrome 2, is related to hypertension, essential and pulmonary hypertension, and has symptoms including vomiting, abnormality of extrapyramidal motor function and lethargy. An important gene associated with Multiple Mitochondrial Dysfunctions Syndrome 2 with Hyperglycinemia is BOLA3 (BolA Family Member 3). Affiliated tissues include spinal cord and endothelial, and related phenotypes are ataxia and visual impairment

UniProtKB/Swiss-Prot : 76 Multiple mitochondrial dysfunctions syndrome 2 with hyperglycinemia: A severe disorder of systemic energy metabolism, resulting in weakness, respiratory failure, lack of neurologic development, lactic acidosis, hyperglycinemia and early death. Some patients show failure to thrive, pulmonary hypertension, hypotonia and irritability. Biochemical features include severe combined deficiency of the 2- oxoacid dehydrogenases, defective lipoic acid synthesis and reduction in activity of mitochondrial respiratory chain complexes.

Related Diseases for Multiple Mitochondrial Dysfunctions Syndrome 2 with...

Diseases related to Multiple Mitochondrial Dysfunctions Syndrome 2 with Hyperglycinemia via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 hypertension, essential 10.1
2 pulmonary hypertension 10.1
3 leukodystrophy 9.9

Symptoms & Phenotypes for Multiple Mitochondrial Dysfunctions Syndrome 2 with...

Human phenotypes related to Multiple Mitochondrial Dysfunctions Syndrome 2 with Hyperglycinemia:

33 (show all 21)
# Description HPO Frequency HPO Source Accession
1 ataxia 33 occasional (7.5%) HP:0001251
2 visual impairment 33 occasional (7.5%) HP:0000505
3 optic atrophy 33 occasional (7.5%) HP:0000648
4 myoclonus 33 occasional (7.5%) HP:0001336
5 seizures 33 HP:0001250
6 spasticity 33 HP:0001257
7 developmental regression 33 HP:0002376
8 global developmental delay 33 HP:0001263
9 hepatomegaly 33 HP:0002240
10 vomiting 33 HP:0002013
11 hypertrophic cardiomyopathy 33 HP:0001639
12 dilated cardiomyopathy 33 HP:0001644
13 lactic acidosis 33 HP:0003128
14 epileptic encephalopathy 33 HP:0200134
15 respiratory failure 33 HP:0002878
16 abnormality of extrapyramidal motor function 33 HP:0002071
17 lethargy 33 HP:0001254
18 generalized hypotonia 33 HP:0001290
19 leukodystrophy 33 HP:0002415
20 poor head control 33 HP:0002421
21 decreased activity of mitochondrial respiratory chain 33 HP:0008972

Symptoms via clinical synopsis from OMIM:

58
Neurologic Central Nervous System:
spasticity
epileptic encephalopathy
lethargy
poor head control
extrapyramidal signs
more
Abdomen Gastrointestinal:
vomiting

Metabolic Features:
lactic acidosis

Muscle Soft Tissue:
hypotonia

Laboratory Abnormalities:
increased serum and urinary lactate
increased urinary 2-hydroxybutyrate
decreased activity of pyruvate dehydrogenase complex
decreased activity of 2-oxoacid dehydrogenases
increased serum glycine
more
Abdomen Liver:
hepatomegaly

Cardiovascular Heart:
hypertrophic cardiomyopathy
dilated cardiomyopathy

Respiratory:
respiratory failure

Head And Neck Eyes:
optic atrophy (in some patients)
visual impairment (in some patients)

Clinical features from OMIM:

614299

UMLS symptoms related to Multiple Mitochondrial Dysfunctions Syndrome 2 with Hyperglycinemia:


vomiting, abnormality of extrapyramidal motor function, lethargy, muscle spasticity

Drugs & Therapeutics for Multiple Mitochondrial Dysfunctions Syndrome 2 with...

Search Clinical Trials , NIH Clinical Center for Multiple Mitochondrial Dysfunctions Syndrome 2 with Hyperglycinemia

Genetic Tests for Multiple Mitochondrial Dysfunctions Syndrome 2 with...

Genetic tests related to Multiple Mitochondrial Dysfunctions Syndrome 2 with Hyperglycinemia:

# Genetic test Affiliating Genes
1 Multiple Mitochondrial Dysfunctions Syndrome 2 30 BOLA3

Anatomical Context for Multiple Mitochondrial Dysfunctions Syndrome 2 with...

MalaCards organs/tissues related to Multiple Mitochondrial Dysfunctions Syndrome 2 with Hyperglycinemia:

42
Spinal Cord, Endothelial

Publications for Multiple Mitochondrial Dysfunctions Syndrome 2 with...

Articles related to Multiple Mitochondrial Dysfunctions Syndrome 2 with Hyperglycinemia:

# Title Authors Year
1
BOLA3 Deficiency Controls Endothelial Metabolism and Glycine Homeostasis in Pulmonary Hypertension. ( 30759996 )
2019
2
Variant non ketotic hyperglycinemia is caused by mutations in LIAS, BOLA3 and the novel gene GLRX5. ( 24334290 )
2014
3
Mutations in iron-sulfur cluster scaffold genes NFU1 and BOLA3 cause a fatal deficiency of multiple respiratory chain and 2-oxoacid dehydrogenase enzymes. ( 21944046 )
2011
4
A novel syndrome affecting multiple mitochondrial functions, located by microcell-mediated transfer to chromosome 2p14-2p13. ( 11156534 )
2001

Variations for Multiple Mitochondrial Dysfunctions Syndrome 2 with...

UniProtKB/Swiss-Prot genetic disease variations for Multiple Mitochondrial Dysfunctions Syndrome 2 with Hyperglycinemia:

76
# Symbol AA change Variation ID SNP ID
1 BOLA3 p.His96Arg VAR_076180 rs148674363
2 BOLA3 p.Ile67Asn VAR_077911 rs550855238

ClinVar genetic disease variations for Multiple Mitochondrial Dysfunctions Syndrome 2 with Hyperglycinemia:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 BOLA3 NM_212552.2(BOLA3): c.123dupA (p.Glu42Argfs) duplication Pathogenic rs869320737 GRCh38 Chromosome 2, 74145235: 74145235
2 BOLA3 NM_212552.2(BOLA3): c.123dupA (p.Glu42Argfs) duplication Pathogenic rs869320737 GRCh37 Chromosome 2, 74372362: 74372362
3 BOLA3 NM_212552.2(BOLA3): c.136C> T (p.Arg46Ter) single nucleotide variant Pathogenic rs143492730 GRCh37 Chromosome 2, 74372349: 74372349
4 BOLA3 NM_212552.2(BOLA3): c.136C> T (p.Arg46Ter) single nucleotide variant Pathogenic rs143492730 GRCh38 Chromosome 2, 74145222: 74145222

Expression for Multiple Mitochondrial Dysfunctions Syndrome 2 with...

Search GEO for disease gene expression data for Multiple Mitochondrial Dysfunctions Syndrome 2 with Hyperglycinemia.

Pathways for Multiple Mitochondrial Dysfunctions Syndrome 2 with...

GO Terms for Multiple Mitochondrial Dysfunctions Syndrome 2 with...

Sources for Multiple Mitochondrial Dysfunctions Syndrome 2 with...

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75 UMLS via Orphanet
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