Mitochondrial disease

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, 11:30 p.m. | Last Modified: 3 Jan 2021, 11:30 p.m.

Panel Version: 0.5896

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
HMG-CoA lyase deficiency, MIM# 246450

Publications

• 8617516

Green List (high evidence)

3-Hydroxy-3-methylglutaric aciduria is a rare autosomal recessive genetic disorder due to a deficiency of the 3-hydroxy-3-methylglutarylCoA lyase (HMG-CoA lyase), a mitochondrial enzyme involved in ketogenesis and in the final step of l-leucine catabolism. A defect in the substrate-generating upstream reactions of OXPHOS. >3 cases reported.
Sources: NHS GMS, Literature

Created: 21 Mar 2020, 5:37 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
HMG-CoA lyase deficiency MIM#246450

Publications

• 25778941
• 11129331
• 19036343