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Mitochondrial HMG-CoA synthase deficiency.

Bram Decru¹, Marine Lys², Kobe Truijens³

¹Clinical Department of Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium; Metabolomics Expertise Center, Center for Cancer Biology, CCB-VIB, VIB-KU Leuven, Leuven, Belgium.

Molecular Genetics and Metabolism

|January 11, 2025

Summary

This summary is machine-generated.

Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2) deficiency impairs ketogenesis. Early diagnosis is crucial, especially in infants, by identifying 4-hydroxy-6-methyl-2-pyrone (4HMP) and abnormal C2/C0 acylcarnitine ratios during metabolic decompensation.

Keywords:

4-hydroxy-6-methyl-2-pyrone HMGCS2 Hypoketotic hypoglycemia Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase

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An In Vitro Approach to Study Mitochondrial Dysfunction: A Cybrid Model

An In Vitro Approach to Study Mitochondrial Dysfunction: A Cybrid Model

Published on: March 9, 2022

Area of Science:

Biochemistry
Genetics
Pediatrics

Background:

Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2) deficiency is a rare, autosomal recessive disorder.
Mutations in the HMGCS2 gene impair ketogenesis, leading to potentially life-threatening metabolic decompensation.

Purpose of the Study:

To systematically review clinical, biochemical, and genetic findings in HMGCS2 deficiency.
To identify key diagnostic markers for this rare metabolic disorder.

Main Methods:

Systematic review of 93 reported cases and 2 new patients.
Analysis of clinical presentations, biochemical abnormalities (organic acids, acylcarnitines), and genetic data.

Main Results:

Onset typically before age 3, with infants facing severe courses, often triggered by gastroenteritis.
Common findings include hypoglycemia, dicarboxyluria, inadequate ketonuria, and elevated dicarboxylic acids.
Key diagnostic indicators are urinary 4-hydroxy-6-methyl-2-pyrone (4HMP) and elevated plasma C2/C0 acylcarnitine ratio.

Conclusions:

HMGCS2 deficiency presents with specific metabolic derangements during decompensation.
Prompt laboratory investigation for 4HMP and C2/C0 acylcarnitine ratio is vital for diagnosis, particularly in infants with unexplained metabolic crises.