Early onset or syndromic epilepsy

Gene: HMGCL

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 and Helen Lord. 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

Green List (high evidence)

AR HMG-CoA lysase defic - rare disorder with the cardinal manifestatons of metabolic acidosis, eleveated urinary organic acid metabolites, dicarboxylic aciduria, hepatomegaly and hyperammonemia. Presenting clinical signis include irritability, lethargy, coma and vomitting. Grunert et al, 2017 - review - collected clinical, biochemical and genetic data in 37 patients (35 families) from metabolic centres in Belgium, Germany, The Netherlands, Switzerland and Turkey. E[pileptic seizures occured in 50% according to table 2.

Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.

Panel Version: 1.188

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
HMG-CoA lyase deficiency,246450

Publications

• 28583327

Green List (high evidence)

Added from Intellectual disability panel update as this gene is also relevant to the Epileptic encephalopathy panel. This is a Confirmed disease gene in Developmental Disorders Genotype-Phenotype Database (DDG2P) for 3-Hydroxy-3-methylglutaryl-CoA lyase deficiency. Grunert (2017) PMID: 28583327 reviewed the clinical presentation and outcome in a series of 37 patients with HMGCLD. 10 had no further metabolic decompensations after diagnosis, and 22 had at least one more metabolic crisis, most often associated with infections, especially gastroenteritis or respiratory tract infections. Half of the patients had normal cognitive development, and the remainder had psychomotor deficits of variable severity.

Created: 18 Dec 2017, 4:15 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
HMG-CoA lyase deficiency, 246450; 3-Hydroxy-3-methylglutaryl-CoA lyase deficiency; HMGCLD

Publications

• 28583327
• 8617516
• 9463337
• 11129331