Early onset or syndromic epilepsy
Gene: MMACHC
Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor. Suggested gene rating: Green.Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.
Panel Version: 1.189
Comment on list classification: Updated rating from Amber to Green: Green review by Zornitza plus sufficient (>3) cases of cblC disease patients with MMACHC variants and seizures from PMIDs 17431913 and 20924684.Created: 3 Dec 2018, 12:15 p.m.
PMID:20924684 (Wang et al, 2010) report 43 patients with combined methylmalonic acidemia and hyperhomocysteinemia (cblC type), 50% of which presented with seizures. Homozygous MMACHC variants are listed in Table 4.Created: 3 Dec 2018, 12:14 p.m.
Ben-Omran et al 2007 (PMID:17431913) report 2 unrelated patients (Pakistani and Bengali descent) with late-onset cblC disease and a homozygous R132X variant in MMACHC. Epileptic seizures were seen amongst the symptoms of both patients.Created: 3 Dec 2018, 10:43 a.m.
Seizures are part of the phenotype of this metabolic disorder.Created: 16 Aug 2018, 12:06 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Methylmalonic aciduria and homocystinuria, cblC type, MIM#277400
Variants in this GENE are reported as part of current diagnostic practice
Source Wessex and West Midlands GLH was added to MMACHC.
Source NHS GMS was added to MMACHC.
Zornitza Stark: Seizures are part of the pheno
Gene: mmachc has been classified as Green List (High Evidence).
Publications for gene: MMACHC were set to
Gene: mmachc has been classified as Green List (High Evidence).
Gene: mmachc has been classified as Green List (High Evidence).
Mode of inheritance for gene: MMACHC was changed from to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MMACHC were changed from to Methylmalonic aciduria and homocystinuria, cblC type, 277400
Expert Review Amber was added to MMACHC. Panel: Genetic Epilepsy Syndromes
MMACHC was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services
MMACHC was created by Sarah Leigh