Early onset or syndromic epilepsy

Gene: MMACHC

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Methylmalonic aciduria and homocystinuria, cblC type, 277400

Publications

• 26283149
• 29068997
• 16311595
• 21748408

I don't know

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.

Green List (high evidence)

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