MCID: 3MT013
MIFTS: 37

3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome

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

Aliases & Classifications for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and...

MalaCards integrated aliases for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome:

Name: 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome 57 12 25 75 29 13 6 15 73
Megdel Syndrome 12 24 53 25 59
Serac1 Defect 24 53 25
Megdel 57 12 75
Mgca6 57 12 75
3-Methylglutaconic Aciduria, Type Vi 57 75
Megdhel Syndrome 24 25
3-Methylglutaconic Aciduria with Dystonia-Deafness, Hepatopathy, Encephalopathy, and Leigh-Like Syndrome; Megdhel 57
3-Methylglutaconic Aciduria with Dystonia-Deafness, Hepatopathy, Encephalopathy, and Leigh-Like Syndrome 57
3-Methylglutaconic Aciduria Type Iv with Sensorineural Deafness, Encephalopathy, and Leigh-Like Syndrome 25
3-Methylglutaconic Aciduria Type Iv with Sensorineural Deafness, Encephalopathy and Leigh-Like Syndrome 73
3-Methylglutaconic Aciduria with Deafness, Encephalopathy, Leigh-Like Syndrome 40
3-Methylglutaconic Aciduria with Deafness, Encephalopathy,leigh-Like Syndrome 24
3-Methylglutaconic Aciduria with Deafness-Encephalopathy-Leigh-Like Syndrome 59
3-Methylglutaconic Aciduria, Type Vi; Mgca6 57
3-Methylglutaconic Aciduria Type Vi 53
3-Methylglutaconic Aciduria Type 6 12
Megdhel 57

Characteristics:

Orphanet epidemiological data:

59
megdel syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
variable severity
onset in infancy or early childhood
there are estimated to be 27 affected children born worldwide each year
one family with a milder disorder without deafness has been reported (last curated february 2018)


HPO:

32
3-methylglutaconic aciduria with deafness, encephalopathy, and leigh-like syndrome:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and...

OMIM : 57 MEGDEL is an autosomal recessive disorder characterized by childhood onset of delayed psychomotor development or psychomotor regression, sensorineural deafness, spasticity or dystonia, and increased excretion of 3-methylglutaconic acid. Brain imaging shows cerebral and cerebellar atrophy as well as lesions in the basal ganglia reminiscent of Leigh syndrome (256000). Laboratory studies show increased serum lactate and alanine, mitochondrial oxidative phosphorylation defects, abnormal mitochondria, abnormal phosphatidylglycerol and cardiolipin profiles in fibroblasts, and abnormal accumulation of unesterified cholesterol within cells (summary by Wortmann et al., 2012). About 50% of patients develop severe, but transient, liver dysfunction and/or signs of liver failure, in the neonatal period or during the first year of life, prompting some authors to suggest the name 'MEGDHEL' syndrome, with the 'H' referring to 'hepatopathy' (summary by Maas et al., 2017). Some patients may have a milder presentation with juvenile-onset spasticity and mild cognitive impairment, indicating a broader phenotypic spectrum (Roeben et al., 2018). For a general phenotypic description and a discussion of genetic heterogeneity of 3-methylglutaconic aciduria, see MGCA type I (250950). (614739)

MalaCards based summary : 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome, also known as megdel syndrome, is related to 3-methylglutaconic aciduria and 3-methylglutaconic aciduria, type iv, and has symptoms including muscle spasticity and abnormality of extrapyramidal motor function. An important gene associated with 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome is SERAC1 (Serine Active Site Containing 1). Affiliated tissues include brain and liver, and related phenotypes are brain atrophy and intellectual disability

UniProtKB/Swiss-Prot : 75 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome: An autosomal recessive disorder characterized by childhood onset of delayed psychomotor development or psychomotor regression, sensorineural deafness, spasticity or dystonia, and increased excretion of 3-methylglutaconic acid. Brain imaging shows cerebral and cerebellar atrophy as well as lesions in the basal ganglia reminiscent of Leigh syndrome. Laboratory studies show increased serum lactate and alanine, mitochondrial oxidative phosphorylation defects, abnormal mitochondria, abnormal phosphatidylglycerol and cardiolipin profiles in fibroblasts, and abnormal accumulation of unesterified cholesterol within cells.

Genetics Home Reference : 25 MEGDEL syndrome is an inherited disorder that affects multiple body systems. It is named for several of its features: 3-methylglutaconic aciduria (MEG), deafness (D), encephalopathy (E), and Leigh-like disease (L).

Disease Ontology : 12 A 3-methylglutaconic aciduria that has material basis in homozygous or compound heterozygous mutation in the SERAC1 gene on chromosome 6q25.

GeneReviews: NBK195853

Related Diseases for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and...

Diseases related to 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 12)
# Related Disease Score Top Affiliating Genes
1 3-methylglutaconic aciduria 26.4 AUH DNAJC19 OPA3 SERAC1 TMEM70
2 3-methylglutaconic aciduria, type iv 26.2 AUH DNAJC19 OPA3 SERAC1 TMEM70
3 encephalopathy 10.1
4 dystonia 10.0
5 leigh syndrome 9.8
6 microcephaly 9.8
7 epilepsy 9.8
8 not otherwise specified 3-mga-uria type 9.8
9 organic acidemia 9.3 SERAC1 TMEM70
10 3-methylglutaconic aciduria, type i 7.9 AUH DNAJC19 OPA3 TMEM70
11 3-methylglutaconic aciduria, type v 7.6 AUH DNAJC19 OPA3 SERAC1 TMEM70
12 3-methylglutaconic aciduria, type iii 7.4 AUH DNAJC19 OPA3 SERAC1 TMEM70

Graphical network of the top 20 diseases related to 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome:



Diseases related to 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome

Symptoms & Phenotypes for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and...

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
brain atrophy
spasticity
dystonia
inability to walk
cerebellar atrophy
more
Head And Neck Eyes:
optic atrophy

Laboratory Abnormalities:
increased serum lactate
hyperammonemia
3-methylglutaconic aciduria
defects in mitochondrial oxidative phosphorylation
abnormal phospholipid profile
more
Muscle Soft Tissue:
hypotonia
degrading mitochondria

Abdomen Gastrointestinal:
feeding problems

Head And Neck Mouth:
oropharyngeal dyskinesia

Growth Other:
failure to thrive

Metabolic Features:
hypoglycemia
lactic acidosis

Immunology:
recurrent infections
neonatal sepsis

Head And Neck Ears:
hearing loss, sensorineural

Head And Neck Head:
microcephaly (1 patient)

Abdomen Liver:
hepatic dysfunction, neonatal period (48%)
liver failure, neonatal period (in some patients), reversible


Clinical features from OMIM:

614739

Human phenotypes related to 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome:

32 (show all 23)
# Description HPO Frequency HPO Source Accession
1 brain atrophy 32 HP:0012444
2 intellectual disability 32 HP:0001249
3 seizures 32 occasional (7.5%) HP:0001250
4 spasticity 32 HP:0001257
5 failure to thrive 32 HP:0001508
6 developmental regression 32 HP:0002376
7 global developmental delay 32 HP:0001263
8 microcephaly 32 occasional (7.5%) HP:0000252
9 sensorineural hearing impairment 32 HP:0000407
10 hypoglycemia 32 HP:0001943
11 feeding difficulties 32 HP:0011968
12 dystonia 32 HP:0001332
13 increased serum lactate 32 HP:0002151
14 lactic acidosis 32 HP:0003128
15 recurrent infections 32 HP:0002719
16 abnormality of extrapyramidal motor function 32 HP:0002071
17 hyperammonemia 32 HP:0001987
18 cerebellar atrophy 32 HP:0001272
19 encephalopathy 32 HP:0001298
20 generalized hypotonia 32 HP:0001290
21 abnormality of the coagulation cascade 32 HP:0003256
22 neonatal sepsis 32 HP:0040187
23 3-methylglutaconic aciduria 32 HP:0003535

UMLS symptoms related to 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome:


muscle spasticity, abnormality of extrapyramidal motor function

Drugs & Therapeutics for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and...

Search Clinical Trials , NIH Clinical Center for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome

Genetic Tests for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and...

Genetic tests related to 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome:

# Genetic test Affiliating Genes
1 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome 29 SERAC1

Anatomical Context for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and...

MalaCards organs/tissues related to 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome:

41
Brain, Liver

Publications for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and...

Articles related to 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome:

# Title Authors Year
1
Dystonia is a Common Phenotypic Feature of MEGDEL Syndrome. ( 29971201 )
2018
2
Diagnosis and Management of Drooling in Children With Progressive Dystonia: A Case Series of Patients With MEGDEL Syndrome. ( 27229007 )
2016
3
Transient neonatal renal failure and massive polyuria in MEGDEL syndrome. ( 27331002 )
2016
4
In-silico modelling of SERAC1: Protein involved in a developmental neural disorder MEGDEL syndrome characterized by 3-methyl glutaconic aciduria type IV with sensory-neural deafness, encephalopathy and Leigh-like syndrome. ( 26531334 )
2015
5
Two Turkish siblings with MEGDEL syndrome due to novel SERAC1 gene mutation. ( 27186703 )
2015
6
MEGDEL Syndrome in a Child From Palestine: Report of a Novel Mutation in SERAC1 Gene. ( 25051967 )
2014
7
Infantile mitochondrial hepatopathy is a cardinal feature of MEGDEL syndrome (3-methylglutaconic aciduria type IV with sensorineural deafness, encephalopathy and Leigh-like syndrome) caused by novel mutations in SERAC1. ( 23918762 )
2013
8
Mutations in the phospholipid remodeling gene SERAC1 cause MEGDEL syndrome. ( 23401890 )
2012
9
MEGDEL Syndrome ( 24741715 )
1993

Variations for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and...

UniProtKB/Swiss-Prot genetic disease variations for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome:

75
# Symbol AA change Variation ID SNP ID
1 SERAC1 p.Gly401Asp VAR_068442
2 SERAC1 p.Gly404Glu VAR_068443
3 SERAC1 p.Ser498Thr VAR_068445 rs201941476

ClinVar genetic disease variations for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome:

6
(show all 24)
# Gene Variation Type Significance SNP ID Assembly Location
1 SERAC1 NM_032861.3(SERAC1): c.442C> T (p.Arg148Ter) single nucleotide variant Pathogenic rs387907236 GRCh37 Chromosome 6, 158567859: 158567859
2 SERAC1 NM_032861.3(SERAC1): c.442C> T (p.Arg148Ter) single nucleotide variant Pathogenic rs387907236 GRCh38 Chromosome 6, 158146827: 158146827
3 SERAC1 NM_032861.3(SERAC1): c.1167_1170delTCAG (p.Gln390Profs) deletion Pathogenic rs772296795 GRCh37 Chromosome 6, 158540199: 158540202
4 SERAC1 NM_032861.3(SERAC1): c.1167_1170delTCAG (p.Gln390Profs) deletion Pathogenic rs772296795 GRCh38 Chromosome 6, 158119167: 158119170
5 SERAC1 NM_032861.3(SERAC1): c.1435_1437delCTT (p.Leu479del) deletion Pathogenic GRCh37 Chromosome 6, 158537281: 158537283
6 SERAC1 NM_032861.3(SERAC1): c.1435_1437delCTT (p.Leu479del) deletion Pathogenic GRCh38 Chromosome 6, 158116249: 158116251
7 SERAC1 NM_032861.3(SERAC1): c.202C> T (p.Arg68Ter) single nucleotide variant Pathogenic rs529232938 GRCh37 Chromosome 6, 158571548: 158571548
8 SERAC1 NM_032861.3(SERAC1): c.202C> T (p.Arg68Ter) single nucleotide variant Pathogenic rs529232938 GRCh38 Chromosome 6, 158150516: 158150516
9 SERAC1 NM_032861.3(SERAC1): c.265_265+1insCATG insertion Likely pathogenic rs797045105 GRCh37 Chromosome 6, 158571484: 158571485
10 SERAC1 NM_032861.3(SERAC1): c.265_265+1insCATG insertion Likely pathogenic rs797045105 GRCh38 Chromosome 6, 158150452: 158150453
11 SERAC1 NM_032861.3(SERAC1): c.1628_1629dupCT (p.Val544Leufs) duplication Pathogenic rs767780913 GRCh37 Chromosome 6, 158535876: 158535877
12 SERAC1 NM_032861.3(SERAC1): c.1628_1629dupCT (p.Val544Leufs) duplication Pathogenic rs767780913 GRCh38 Chromosome 6, 158114844: 158114845
13 SERAC1 NM_032861.3(SERAC1): c.1643_1646dup (p.Leu550Serfs) duplication Pathogenic rs761964407 GRCh37 Chromosome 6, 158535859: 158535862
14 SERAC1 NM_032861.3(SERAC1): c.1643_1646dup (p.Leu550Serfs) duplication Pathogenic rs761964407 GRCh38 Chromosome 6, 158114827: 158114830
15 SERAC1 NM_032861.3(SERAC1): c.1403+1G> C single nucleotide variant Pathogenic rs1131690799 GRCh38 Chromosome 6, 158117726: 158117726
16 SERAC1 NM_032861.3(SERAC1): c.1403+1G> C single nucleotide variant Pathogenic rs1131690799 GRCh37 Chromosome 6, 158538758: 158538758
17 SERAC1 NM_032861.3(SERAC1): c.1577G> A (p.Gly526Glu) single nucleotide variant Pathogenic GRCh38 Chromosome 6, 158114896: 158114896
18 SERAC1 NM_032861.3(SERAC1): c.1577G> A (p.Gly526Glu) single nucleotide variant Pathogenic GRCh37 Chromosome 6, 158535928: 158535928
19 SERAC1 NM_032861.3(SERAC1): c.91+6T> C single nucleotide variant Likely pathogenic GRCh37 Chromosome 6, 158579299: 158579299
20 SERAC1 NM_032861.3(SERAC1): c.91+6T> C single nucleotide variant Likely pathogenic GRCh38 Chromosome 6, 158158267: 158158267
21 SERAC1 NM_032861.3(SERAC1): c.21C> A (p.Cys7Ter) single nucleotide variant Likely pathogenic rs139301835 GRCh38 Chromosome 6, 158158343: 158158343
22 SERAC1 NM_032861.3(SERAC1): c.21C> A (p.Cys7Ter) single nucleotide variant Likely pathogenic rs139301835 GRCh37 Chromosome 6, 158579375: 158579375
23 SERAC1 NM_032861.3(SERAC1): c.660A> G (p.Gln220=) single nucleotide variant Uncertain significance rs776026202 GRCh38 Chromosome 6, 158143134: 158143134
24 SERAC1 NM_032861.3(SERAC1): c.660A> G (p.Gln220=) single nucleotide variant Uncertain significance rs776026202 GRCh37 Chromosome 6, 158564166: 158564166

Expression for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and...

Search GEO for disease gene expression data for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome.

Pathways for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and...

GO Terms for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and...

Cellular components related to 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.02 AUH DNAJC19 OPA3 SERAC1 TMEM70

Biological processes related to 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 visual perception GO:0007601 8.62 DNAJC19 OPA3

Sources for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and...

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