Fatty Acid Oxidation Defects

Gene: HMGCL

Green List (high evidence)

3-Hydroxy-3-methylglutaryl coenzyme A lyase catalyzes the cleavage of HMG-CoA to acetoacetic acid and acetyl-CoA, the last step of both ketogenesis and leucine catabolism. It is located in both the mitochondrial matrix and the peroxisomes.

The disorder causes metabolic acidosis without ketonuria, hypoglycaemia, and a characteristic pattern of elevated urinary organic acid metabolites, including 3-hydroxy-3-methylglutaric, 3-methylglutaric, and 3-hydroxyisovaleric acids. Urinary levels of 3-methylcrotonylglycine may be increased. Dicarboxylic aciduria, hepatomegaly, and hyperammonaemia may also be observed. Presenting clinical signs include irritability, lethargy, coma, and vomiting.

Well established gene-disease association. Large gene deletions reported.

Created: 3 Jan 2021, 11:27 p.m. | Last Modified: 3 Jan 2021, 11:27 p.m.

Panel Version: 0.72

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
HMG-CoA lyase deficiency, MIM# 246450

Publications

• 8617516