Evidence of docosahexaenoic acid deficiency in maple syrup urine disease: insights from plasma long-chain polyunsaturated fatty acid status

BACKGROUND: Maple syrup urine disease (MSUD) is an inherited metabolic disorder requiring protein restriction, often limiting intake of animal-derived foods. This raises concerns about long-chain polyunsaturated fatty acid (LC-PUFA) status. The primary aim of this study is to evaluate plasma n-3 and n-6 fatty acid levels in MSUD patients. METHODS: This single-center, cross-sectional study included 16 MSUD patients and 22 unaffected siblings sharing a similar household and environmental background. Dietary intake was recorded and plasma fatty acid profiles were analyzed. RESULTS: Dietary assessments revealed significantly lower intakes of total fat and cholesterol (both p < 0.001) and n-3 PUFAs (p = 0.036) in MSUD patients, with alpha-linolenic acid (ALA) intake as the only individual LC-PUFA significantly reduced (p = 0.048). Plasma analysis showed significantly lower docosahexaenoic acid (DHA) levels in patients despite similar dietary DHA intake (p < 0.001), while arachidonic acid and mead acid were significantly elevated (both p < 0.001). Although plasma DHA concentrations showed a moderate positive correlation with dietary ALA intake (r = 0.516, p = 0.041), regression analysis showed that neither dietary ALA intake (B = 0.005, p = 0.584) nor the dietary n-6/n-3 PUFA ratio (B = -0.552, p = 0.706) independently predicted plasma DHA levels. In the MSUD group, plasma DHA levels were positively associated with dietary leucine intake (r = 0.635, p = 0.008) and plasma isoleucine concentrations (r = 0.524, p = 0.037). CONCLUSION: Our findings provide evidence of DHA deficiency in MSUD patients, which may result from both inadequate dietary intake and changes in n-3 PUFA metabolism, highlighting the need to investigate additional contributing mechanisms.