Mimicking Ketonuria in the Ketogenesis Defect 3-Hydroxy-3-Methylglutaryl-Coenzyme A Lyase Deficiency

Abstract

3-Hydroxy-3-methylglutaryl-coenzyme A lyase (HMGCL, HMGCL) deficiency is a rare inborn error of ketogenesis. Even if the ketogenic enzyme is fully disrupted, an elevated signal for the ketone body acetoacetic acid is a frequent observation in the analysis of urinary organic acids, at least if derivatization is performed by methylation. We provide an explanation for this phenomenon and trace it back to degradation of the derivatized 3-hydroxy-3-methylglutaric acid and high temperature of the injector of the gas chromatograph.

Inborn Errors of Ketone Body Metabolism and Transport

“…Of technical note, it was recently demonstrated that following methylation for organic acid analysis in HMGCL deficiency, derivatized acetoacetate can be formed as a chemical artifact by the temperature-dependent degradation of derivatized 3-hydroxy-3-methylglutaric acid in the GC injector. 18 Eight pregnancies in 5 women with HMGCL deficiency have been reported. [19][20][21][22] Five pregnancies resulted in the birth of a healthy child at term.…”

“…Of technical note, it was recently demonstrated that following methylation for organic acid analysis in HMGCL deficiency, derivatized acetoacetate can be formed as a chemical artifact by the temperature-dependent degradation of derivatized 3-hydroxy-3-methylglutaric acid in the GC injector. 18…”