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Inborn errors of metabolism

Gene: HMGCL

Green List (high evidence)

HMGCL (3-hydroxymethyl-3-methylglutaryl-CoA lyase)
EnsemblGeneIds (GRCh38): ENSG00000117305
EnsemblGeneIds (GRCh37): ENSG00000117305
OMIM: 613898, Gene2Phenotype
HMGCL is in 11 panels

4 reviews

Sarah Leigh (Genomics England Curator)

Comment 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

Anna de Burca (Genomics England Curator)

Green List (high evidence)

Potential differential diagnosis for mitochondrial disorder, with elevated lactate, seizures, basal ganglia abnormalilty etc
Created: 19 Jun 2019, 12:26 p.m.

Phenotypes
HMG-CoA lyase deficiency, 246450

Carl Fratter (Oxford University Hospitals NHS Trust)

Red List (low evidence)

Red - fatty acid oxidation disorder, rather than a primary mitochondrial disorder
Created: 11 Jun 2019, 3:59 p.m.

Phenotypes
HMG-CoA lyase deficiency, 246450

Louise Daugherty (Genomics England Curator)

Green List (high evidence)

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

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Red
  • London North GLH
  • NHS GMS
  • Expert Review Green
  • Other
Phenotypes
  • 3-Hydroxy-3-methyl glutaric aciduria (Organic acidurias)
  • 3-Hydroxy-3-methylglutaryl-CoA lyase deficiency
  • HMG-CoA lyase deficiency, 246450
  • HMGCLD
OMIM
613898
Clinvar variants
Variants in HMGCL
Penetrance
None
Publications
Panels with this gene

History Filter Activity

13 Feb 2019, Gel status: 4

Added New Source, Added New Source

Ivone Leong (Genomics England Curator)

Source NHS GMS was added to HMGCL. Source London North GLH was added to HMGCL.

8 Jan 2019, Gel status: 4

Panel promoted to version 1.0

Ellen McDonagh (Genomics England Curator)

Ellen McDonagh: Comment on mode of pathogenici

16 Dec 2018, Gel status: 4

Set Phenotypes, Set publications

Ellen McDonagh (Genomics England Curator)

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

16 Dec 2018, Gel status: 4

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Ellen McDonagh (Genomics England Curator)

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