Ketotic hypoglycaemia
Gene: MCEE

MCEE (methylmalonyl-CoA epimerase)
EnsemblGeneIds (GRCh38): ENSG00000124370
EnsemblGeneIds (GRCh37): ENSG00000124370
OMIM: 608419, Gene2Phenotype
MCEE is in 8 panels

2 reviews

Alexander Broomfield (Central Manchester Foundation Trust)

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Ellen McDonagh (Genomics England Curator)

Comment when marking as ready: Confirmed that mode of inheritance should remain biallelic, despite PMID: 17823972 reporting two cell lines from patients as heterozygous, as the vast majority of reports say homozygous, as well as Gene2Phenotype, OMIM, UKGTN and Illumina sources.
Created: 14 Jun 2016, 8:07 a.m.

Comment on list classification: Gene added by reviewer and rated as green for inclusion on this panel. It is a confirmed DD gene for Methylmalonyl-CoA epimerase deficiency, and more than 3 family reports have now been published, though it seems to be a rare cause of methylmalonyl-CoA epimerase deficiency and patients may have mild symptoms. Two cases in where the patient were also homozygous for variants in another gene in the pathway.
Created: 8 Jun 2016, 1:01 p.m.

Comment on mode of inheritance: Mode of inheritance confirmed in OMIM and G2P, and review.
Created: 20 Apr 2016, 1:25 p.m.

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

Expert Review Green
Expert Review
Emory Genetics Laboratory
Radboud University Medical Center, Nijmegen
UKGTN
Illumina TruGenome Clinical Sequencing Services

Phenotypes

metabolic encephalopathy with hyperammonaemia, hypotonia, recurrent episodes of ketoacidosis, liver impairment, psychomotor retardation, recurrent infections
Methylmalonyl-CoA epimerase deficiency

OMIM

608419

Clinvar variants

Variants in MCEE

Penetrance

Complete

Publications

16697227 - proband and sibling with mild methylmalonic aciduria were found to be homozygous for the c.139C>T, p.R47X variant, with heterozygous unaffected parents
16752391 (a case report of a patient who was homozygous for the R47X variant in MCEE, but also homozygous for a second variant in the SPR gene)
25763508 (a case homozygous for c.139C>T, p.Arg47* in the MCEE gene, and c.751A>T, p.Lys251* in the SRD gene
17823972 - sequencing of cell lines from 229 patients with elevations of methylmalonic acid excretion for which no cause was known identified 5 cell lines with MCEE variants. In fibroblast lines from two patients with the c.139C>T, p.R47X variant, WT cDNA corrected the biochemical phenotype in the cells.
16697227 - proband and sibling with mild methylmalonic aciduria were found to be homozygous for the c.139C>T, p.R47X variant, with heterozygous unaffected parents
16752391 (a case report of a patient who was homozygous for the R47X variant in MCEE, but also homozygous for a second variant in the SPR gene)
25763508 (a case homozygous for c.139C>T, p.Arg47* in the MCEE gene, and c.751A>T, p.Lys251* in the SRD gene
17823972 - sequencing of cell lines from 229 patients with elevations of methylmalonic acid excretion for which no cause was known identified 5 cell lines with MCEE variants. In fibroblast lines from two patients with the c.139C>T, p.R47X variant, WT cDNA corrected the biochemical phenotype in the cells.

Panels with this gene