Familial glycerol kinase deficiency uncovered by triglyceride-lipemic index discordance

Pseudohypertriglyceridemia caused by elevated free glycerol is an uncommon analytical interference that may lead to misdiagnosis and unnecessary treatment. Because most routine enzymatic triglyceride assays do not incorporate glycerol blanking, triglyceride concentrations may be overestimated in patients with hyperglycerolemia. Recognition of triglyceride-lipemic index (L-index) discordance may facilitate the identification of glycerol interference in clinical laboratory practice.

We investigated a patient with persistent severe hypertriglyceridemia who repeatedly showed a negative L-index. The unexpected absence of lipemia prompted investigation for glycerol interference.

A 78-year-old man showed persistently elevated triglyceride concentrations ranging from 844 to 1864 mg/dL over a five-year period despite lipid-lowering therapy, while L-index remained consistently negative. Markedly elevated free glycerol (12,600 μmol/L) confirmed pseudohypertriglyceridemia due to hyperglycerolemia. Exome sequencing identified a previously unreported hemizygous likely pathogenic GK variant (NM_001205019.2:c.1 A > G), affecting the translation initiation codon. Targeted familial testing identified the same variant in an affected maternal nephew with a concordant biochemical phenotype.

Triglyceride-L-index discordance represents an easily recognizable analytical pattern that can be incorporated into routine laboratory workflows. We propose a practical laboratory algorithm to facilitate recognition of pseudohypertriglyceridemia and earlier diagnosis of glycerol kinase deficiency.