Definition

HMG-CoA lyase deficiency is an organic acidemia/fatty acid oxidation disorder caused by biallelic pathogenic variants in the HMGCL gene, resulting in deficiency of the mitochondrial enzyme 3-hydroxy-3-methylglutaryl-CoA lyase. The enzyme functions both in the final step of leucine catabolism and in ketogenesis; its deficiency causes hypoketotic hypoglycemia, hyperammonemia and metabolic acidosis during periods of fasting or illness.

Gene/region examined

HMGCL - Exon 1, HMGCL - Exon 2, HMGCL - Exon 3, HMGCL - Exon 4, HMGCL - Exon 5, HMGCL - Exon 6, HMGCL - Exon 7, HMGCL - Exon 8, HMGCL - Exon 9

Method

Sequence analysis

Accepted sample types

EDTA blood, AF, CVS

Inheritance

Hereditary, autosomal recessive.

Related Tests

Inheritance Patterns

Describes how a genetic condition is passed on within a family. There are five main patterns

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Carrier (Heterozygous / Homozygous)

Why it matters: In autosomal recessive inheritance, when each parent is a carrier (while both appear healthy), the chance of their child being born with the disease is 25% in each

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VUS (Variant of Uncertain Significance)

This is the situation where the test has detected a change in the DNA, but the role of this change in the development of disease is unconfirmed.

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How to Read a Genetic Test Result (Positive / Negative / VUS)

A genetic test result falls into three main categories

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Types of Genetic Tests

A genetic test is a type of medical test that detects changes in genes, chromosomes or proteins. Today there are more than 77,000 genetic tests available.

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