Likely inborn error of metabolism - targeted testing not possible
Gene: HMGCLComment on list classification: HMGCL is being demoted to Red on this panel on the recommendation of the GMS mitochondrial specialist test group, including by Carl Fratter (Oxford University Hospitals NHS Trust). It is associated with HMG-CoA lyase deficiency 246450, with microcephaly, seizures & metabolic disturbance. Although this is technically a mitochondrial disorder, the phenotype is quite different to other mitochondrial conditions.Created: 1 Aug 2019, 1:35 p.m. | Last Modified: 1 Aug 2019, 1:35 p.m.
Panel Version: 1.416
Potential differential diagnosis for mitochondrial disorder, with elevated lactate, seizures, basal ganglia abnormalilty etcCreated: 19 Jun 2019, 12:26 p.m.
Phenotypes
HMG-CoA lyase deficiency, 246450
Red - fatty acid oxidation disorder, rather than a primary mitochondrial disorderCreated: 11 Jun 2019, 3:59 p.m.
Phenotypes
HMG-CoA lyase deficiency, 246450
Added from Intellectual disability panel update as this gene is also relevant to theMitochondrial disorders 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; intellectual disability
Publications
Source: Expert Review Red was removed from gene: HMGCL
Source NHS GMS was added to HMGCL. Source London North GLH was added to HMGCL.
Ellen McDonagh: Comment on mode of pathogenici
Added phenotypes 3-Hydroxy-3-methyl glutaric aciduria (Organic acidurias) for gene: HMGCL Publications for gene HMGCL were changed from 8617516; 28583327; 9463337; 11129331 to 27604308
gene: HMGCL was added gene: HMGCL was added to Inborn errors of metabolism. Sources: Expert Review Green Mode of inheritance for gene: HMGCL was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: HMGCL were set to 8617516; 28583327; 9463337; 11129331 Phenotypes for gene: HMGCL were set to 3-Hydroxy-3-methylglutaryl-CoA lyase deficiency; HMG-CoA lyase deficiency, 246450; HMGCLD