MCID: MLT150
MIFTS: 21

Multiple Mitochondrial Dysfunctions Syndrome 2 with Hyperglycinemia

Categories: Genetic diseases, Neuronal diseases, Metabolic 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 57 75
Mmds2 57 75
Mitochondrial Dysfunctions Syndrome, Multiple, Type 2 40
Multiple Mitochondrial Dysfunctions Syndrome Type 2 59
Multiple Mitochondrial Dysfunctions Syndrome 2 73
Bola3 Deficiency 59

Characteristics:

Orphanet epidemiological data:

59
multiple mitochondrial dysfunctions syndrome type 2
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Neonatal;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy
death in early childhood may occur


HPO:

32
multiple mitochondrial dysfunctions syndrome 2 with hyperglycinemia:
Mortality/Aging death in infancy
Onset and clinical course infantile onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Multiple Mitochondrial Dysfunctions Syndrome 2 with...

OMIM : 57 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, is also known as mmds2, and has symptoms including lethargy, muscle spasticity and vomiting. An important gene associated with Multiple Mitochondrial Dysfunctions Syndrome 2 with Hyperglycinemia is BOLA3 (BolA Family Member 3). Affiliated tissues include spinal cord, and related phenotypes are seizures and ataxia

UniProtKB/Swiss-Prot : 75 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...

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

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
spasticity
lethargy
poor head control
epileptic encephalopathy
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

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

32 (show all 20)
# Description HPO Frequency HPO Source Accession
1 seizures 32 HP:0001250
2 ataxia 32 occasional (7.5%) HP:0001251
3 spasticity 32 HP:0001257
4 global developmental delay 32 HP:0001263
5 hepatomegaly 32 HP:0002240
6 visual impairment 32 occasional (7.5%) HP:0000505
7 optic atrophy 32 occasional (7.5%) HP:0000648
8 vomiting 32 HP:0002013
9 hypertrophic cardiomyopathy 32 HP:0001639
10 myoclonus 32 occasional (7.5%) HP:0001336
11 lactic acidosis 32 HP:0003128
12 respiratory failure 32 HP:0002878
13 abnormality of extrapyramidal motor function 32 HP:0002071
14 lethargy 32 HP:0001254
15 dilated cardiomyopathy 32 HP:0001644
16 leukodystrophy 32 HP:0002415
17 generalized hypotonia 32 HP:0001290
18 poor head control 32 HP:0002421
19 epileptic encephalopathy 32 HP:0200134
20 decreased activity of mitochondrial respiratory chain 32 HP:0008972

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


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

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...

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

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

41
Spinal Cord

Publications for Multiple Mitochondrial Dysfunctions Syndrome 2 with...

Variations for Multiple Mitochondrial Dysfunctions Syndrome 2 with...

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

75
# 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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