Elevated Plasma Vitamin B₁₂ in Patients with Hepatic Glycogen Storage Diseases

Background: Hepatic glycogen storage diseases (GSDs) are inborn errors of metabolism affecting the synthesis or breakdown of glycogen in the liver. This study, for the first time, systematically assessed vitamin B₁₂ status in a large cohort of hepatic GSD patients. Methods: Plasma vitamin B₁₂, total plasma homocysteine (tHcy) and methylmalonic acid concentrations were measured in 44 patients with hepatic GSDs and compared to 42 healthy age- and gender-matched controls. Correlations of vitamin B₁₂ status with different disease markers of GSDs (including liver transaminase activities and triglycerides) as well as the vitamin B₁₂ intake were studied. Results: GSD patients had significantly higher plasma vitamin B₁₂ concentrations than healthy controls (p = 0.0002). Plasma vitamin B₁₂ concentration remained elevated in GSD patients irrespective of vitamin B₁₂ intake. Plasma vitamin B₁₂ concentrations correlated negatively with triglyceride levels, whereas no correlations were detected with liver transaminase activities (GOT and GPT) in GSD patients. Merging biomarker data of healthy controls and GSD patients showed a positive correlation between vitamin B₁₂ status and liver function, which suggests complex biomarker associations. A combined analysis of biomarkers permitted a reliable clustering of healthy controls versus GSD patients. Conclusions: Elevated plasma concentration of vitamin B₁₂ (irrespective of B₁₂ intake) is a common finding in patients with hepatic GSD. The negative correlation of plasma vitamin B₁₂ with triglyceride levels suggests an influence of metabolic control on the vitamin B₁₂ status of GSD patients. Elevated vitamin B₁₂ was not correlated with GOT and GPT in our cohort of GSD patients. Merging of data from healthy controls and GSD patients yielded positive correlations between these biomarkers. This apparent dichotomy highlights the intrinsic complexity of biomarker associations and argues against generalizations of liver disease and elevated vitamin B₁₂ in blood. Further studies are needed to determine whether the identified associations are causal or coincidental, and the possible impact of chronically elevated vitamin B₁₂ on GSD.