MEGDEL
MCID: 3MT013
MIFTS: 38

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

Categories: Ear diseases, Fetal diseases, Genetic diseases, Metabolic diseases, Neuronal diseases, Rare 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 58 12 26 76 30 13 6 15 74
Megdel Syndrome 12 25 54 26 60
Serac1 Defect 25 54 26
Megdel 58 12 76
Mgca6 58 12 76
3-Methylglutaconic Aciduria with Dystonia-Deafness, Hepatopathy, Encephalopathy, and Leigh-Like Syndrome 58 76
3-Methylglutaconic Aciduria, Type Vi 58 76
Megdhel Syndrome 25 26
Megdhel 58 76
3-Methylglutaconic Aciduria with Dystonia-Deafness, Hepatopathy, Encephalopathy, and Leigh-Like Syndrome; Megdhel 58
3-Methylglutaconic Aciduria Type Iv with Sensorineural Deafness, Encephalopathy, and Leigh-Like Syndrome 26
3-Methylglutaconic Aciduria Type Iv with Sensorineural Deafness, Encephalopathy and Leigh-Like Syndrome 74
3-Methylglutaconic Aciduria with Deafness, Encephalopathy, Leigh-Like Syndrome 41
3-Methylglutaconic Aciduria with Deafness, Encephalopathy,leigh-Like Syndrome 25
3-Methylglutaconic Aciduria with Deafness-Encephalopathy-Leigh-Like Syndrome 60
3-Methylglutaconic Aciduria, Type Vi; Mgca6 58
3-Methylglutaconic Aciduria Type Vi 54
3-Methylglutaconic Aciduria Type 6 12

Characteristics:

Orphanet epidemiological data:

60
megdel syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

58
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:

33
3-methylglutaconic aciduria with deafness, encephalopathy, and leigh-like syndrome:
Onset and clinical course variable expressivity
Inheritance autosomal recessive inheritance


Classifications:



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

OMIM : 58 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 abnormality of extrapyramidal motor function and muscle spasticity. 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 seizures and microcephaly

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

Genetics Home Reference : 26 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).

UniProtKB/Swiss-Prot : 76 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.

Wikipedia : 77 Serine active site-containing protein 1, or Protein SERAC1 is a protein in humans that is encoded by the... more...

GeneReviews: NBK195853

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

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...

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

33 (show all 25)
# Description HPO Frequency HPO Source Accession
1 seizures 33 occasional (7.5%) HP:0001250
2 microcephaly 33 occasional (7.5%) HP:0000252
3 brain atrophy 33 HP:0012444
4 intellectual disability 33 HP:0001249
5 spasticity 33 HP:0001257
6 failure to thrive 33 HP:0001508
7 developmental regression 33 HP:0002376
8 global developmental delay 33 HP:0001263
9 sensorineural hearing impairment 33 HP:0000407
10 hypoglycemia 33 HP:0001943
11 feeding difficulties 33 HP:0011968
12 absent speech 33 HP:0001344
13 dystonia 33 HP:0001332
14 inability to walk 33 HP:0002540
15 increased serum lactate 33 HP:0002151
16 lactic acidosis 33 HP:0003128
17 recurrent infections 33 HP:0002719
18 abnormality of extrapyramidal motor function 33 HP:0002071
19 hyperammonemia 33 HP:0001987
20 cerebellar atrophy 33 HP:0001272
21 generalized hypotonia 33 HP:0001290
22 encephalopathy 33 HP:0001298
23 abnormality of the coagulation cascade 33 HP:0003256
24 neonatal sepsis 33 HP:0040187
25 3-methylglutaconic aciduria 33 HP:0003535

Symptoms via clinical synopsis from OMIM:

58
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

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


abnormality of extrapyramidal motor function, muscle spasticity

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 30 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:

42
Brain, Liver

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

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

(show all 12)
# Title Authors Year
1
Dystonia is a Common Phenotypic Feature of MEGDEL Syndrome. ( 29971201 )
2018
2
Adult-onset Generalized Dystonia as the Main Manifestation of MEGDEL Syndrome. ( 29686941 )
2018
3
MEGDEL Syndrome: Expanding the Phenotype and New Mutations. ( 28505671 )
2017
4
Diagnosis and Management of Drooling in Children With Progressive Dystonia: A Case Series of Patients With MEGDEL Syndrome. ( 27229007 )
2016
5
Transient neonatal renal failure and massive polyuria in MEGDEL syndrome. ( 27331002 )
2016
6
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
7
Two Turkish siblings with MEGDEL syndrome due to novel SERAC1 gene mutation. ( 27186703 )
2015
8
REMOVED: 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. ( 29887041 )
2015
9
MEGDEL Syndrome in a Child From Palestine: Report of a Novel Mutation in SERAC1 Gene. ( 25051967 )
2014
10
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
11
Mutations in the phospholipid remodeling gene SERAC1 cause MEGDEL syndrome. ( 23401890 )
2012
12
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:

76
# 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 34)
# Gene Variation Type Significance SNP ID Assembly Location
1 SERAC1 NM_032861.3(SERAC1): c.265_265+1insCATG insertion Likely pathogenic rs797045105 GRCh37 Chromosome 6, 158571484: 158571485
2 SERAC1 NM_032861.3(SERAC1): c.265_265+1insCATG insertion Likely pathogenic rs797045105 GRCh38 Chromosome 6, 158150452: 158150453
3 SERAC1 NM_032861.3(SERAC1): c.1628_1629dupCT (p.Val544Leufs) duplication Pathogenic rs767780913 GRCh37 Chromosome 6, 158535876: 158535877
4 SERAC1 NM_032861.3(SERAC1): c.1628_1629dupCT (p.Val544Leufs) duplication Pathogenic rs767780913 GRCh38 Chromosome 6, 158114844: 158114845
5 SERAC1 NM_032861.3(SERAC1): c.442C> T (p.Arg148Ter) single nucleotide variant Pathogenic rs387907236 GRCh37 Chromosome 6, 158567859: 158567859
6 SERAC1 NM_032861.3(SERAC1): c.442C> T (p.Arg148Ter) single nucleotide variant Pathogenic rs387907236 GRCh38 Chromosome 6, 158146827: 158146827
7 SERAC1 NM_032861.3(SERAC1): c.1167_1170delTCAG (p.Gln390Profs) deletion Pathogenic rs772296795 GRCh37 Chromosome 6, 158540199: 158540202
8 SERAC1 NM_032861.3(SERAC1): c.1167_1170delTCAG (p.Gln390Profs) deletion Pathogenic rs772296795 GRCh38 Chromosome 6, 158119167: 158119170
9 SERAC1 NM_032861.3(SERAC1): c.1435_1437delCTT (p.Leu479del) deletion Pathogenic rs1199625391 GRCh37 Chromosome 6, 158537281: 158537283
10 SERAC1 NM_032861.3(SERAC1): c.1435_1437delCTT (p.Leu479del) deletion Pathogenic rs1199625391 GRCh38 Chromosome 6, 158116249: 158116251
11 SERAC1 NM_032861.3(SERAC1): c.202C> T (p.Arg68Ter) single nucleotide variant Pathogenic rs529232938 GRCh37 Chromosome 6, 158571548: 158571548
12 SERAC1 NM_032861.3(SERAC1): c.202C> T (p.Arg68Ter) single nucleotide variant Pathogenic rs529232938 GRCh38 Chromosome 6, 158150516: 158150516
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 Uncertain significance rs1554261079 GRCh38 Chromosome 6, 158114896: 158114896
18 SERAC1 NM_032861.3(SERAC1): c.1577G> A (p.Gly526Glu) single nucleotide variant Uncertain significance rs1554261079 GRCh37 Chromosome 6, 158535928: 158535928
19 SERAC1 NM_032861.3(SERAC1): c.91+6T> C single nucleotide variant Likely pathogenic rs1554265452 GRCh37 Chromosome 6, 158579299: 158579299
20 SERAC1 NM_032861.3(SERAC1): c.91+6T> C single nucleotide variant Likely pathogenic rs1554265452 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 GRCh37 Chromosome 6, 158564166: 158564166
24 SERAC1 NM_032861.3(SERAC1): c.660A> G (p.Gln220=) single nucleotide variant Uncertain significance rs776026202 GRCh38 Chromosome 6, 158143134: 158143134
25 SERAC1 NM_032861.3(SERAC1): c.91A> G (p.Arg31Gly) single nucleotide variant Uncertain significance GRCh37 Chromosome 6, 158579305: 158579305
26 SERAC1 NM_032861.3(SERAC1): c.91A> G (p.Arg31Gly) single nucleotide variant Uncertain significance GRCh38 Chromosome 6, 158158273: 158158273
27 SERAC1 NM_032861.3(SERAC1): c.1084A> T (p.Ile362Phe) single nucleotide variant Uncertain significance GRCh37 Chromosome 6, 158541539: 158541539
28 SERAC1 NM_032861.3(SERAC1): c.1084A> T (p.Ile362Phe) single nucleotide variant Uncertain significance GRCh38 Chromosome 6, 158120507: 158120507
29 SERAC1 NM_032861.3(SERAC1): c.92-239G> C single nucleotide variant Pathogenic GRCh37 Chromosome 6, 158576622: 158576622
30 SERAC1 NM_032861.3(SERAC1): c.92-239G> C single nucleotide variant Pathogenic GRCh38 Chromosome 6, 158155590: 158155590
31 SERAC1 NM_032861.3(SERAC1): c.92-165C> T single nucleotide variant Pathogenic GRCh37 Chromosome 6, 158576548: 158576548
32 SERAC1 NM_032861.3(SERAC1): c.92-165C> T single nucleotide variant Pathogenic GRCh38 Chromosome 6, 158155516: 158155516
33 SERAC1 NM_032861.4(SERAC1): c.92-13_92-10del deletion Uncertain significance GRCh38 Chromosome 6, 158155361: 158155364
34 SERAC1 NM_032861.4(SERAC1): c.92-13_92-10del deletion Uncertain significance GRCh37 Chromosome 6, 158576393: 158576396

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 mitochondrial inner membrane GO:0005743 9.13 AGK DNAJC19 TMEM70
2 mitochondrion GO:0005739 9.02 AGK AUH DNAJC19 SERAC1 TMEM70

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

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