Hyperhomocysteinemia and Vitamin B Deficiency as Potential Aggravating Factors in Huntington's Disease: A Prospective Monocentric Study

Abstract Background Although not confirmed, some studies have suggested that elevated homocysteine levels are common in patients with Huntington's disease (HD). Its clinical relevance remains unclear. Objectives We aimed to assess vitamin B and homocysteine levels in HD patients and explore the relationships among hyperhomocysteinemia, vitamin B deficiency, and motor symptom progression. Methods In this monocentric case–control study, 77 HD patients were prospectively included between January 2020 and June 2023 at Nancy University Hospital. As controls, biological data were obtained retrospectively from 87 individuals referred to the Metabolic Medicine Department between January 2017 and February 2025. HD patients underwent clinical (Unified Huntington Disease Rating Scale‐Motor) and biochemical (vitamin B and homocysteine levels) evaluations. Fisher's exact test, Wilcoxon test, or Student's t‐test were used, with P < 0.05 considered significant. Results HD patients—both symptomatic and premanifest—had significantly higher homocysteine levels than did controls. Hyperhomocysteinemia was found in 36 patients (≈48%) and was associated with faster motor progression ( P < 0.001). Conclusions Hyperhomocysteinemia appears to be frequent in HD patients and may represent a risk factor contributing to phenotypic variability. These findings support a potential link between altered one‐carbon metabolism and HD. Further longitudinal and mechanistic studies are needed to clarify the clinical and pathophysiological relevance of homocysteine metabolism in HD and to determine whether targeting hyperhomocysteinemia could have therapeutic implications. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.