メープルシロップ尿症

Diseases that cause neurological dysfunction, such as Parkinson's disease (PD), Alzheimer's disease (AD), and maple syrup urine disease (MSUD), among others, are characterized by complex and multifaceted etiologies. There is growing evidence that branched-chain amino acids (BCAAs), regulated by the gut microbiota, play a critical role in the development of the central nervous system (CNS) disorders. This review focuses on the potential role of branched-chain amino acid metabolism in regulating brain function and gut microbiota. First, we summarize the current understanding of BCAAs, encompassing their biochemical metabolism, function, and systemic metabolic mechanisms. Subsequently, we delve into the mechanisms through which the gut microbiota regulates branched-chain amino acid metabolism, along with its mechanistic insights and recent evidence of its impact on neurological disorders. Finally, we discuss future research directions and challenges regarding gut BCAAs metabolism as a potential treatment for brain and gastrointestinal dysfunction.

Lipid emulsion has several established clinical uses, including parenteral nutrition, treatment of local anaesthetic systemic toxicity and as an energy source in metabolic crises, such as maple syrup urine disease. In toxicological settings, it acts via a 'lipid sink' mechanism, sequestering lipophilic drugs and reducing their bioavailability. This raises the possibility that the pharmacokinetics of commonly used anaesthetic agents may be affected in patients with a high intravascular lipid load. We report the peri-operative management of a 14-year-old child with maple syrup urine disease receiving a high-dose lipid emulsion infusion during a metabolic crisis, who required general anaesthesia and intubation to facilitate transfer to a specialist paediatric centre. During induction of anaesthesia, fentanyl appeared to have a minimal sedating effect. Ketamine was avoided due to concerns regarding unpredictable efficacy in the setting of lipid loading. The patient also developed significant hypotension during maintenance with sevoflurane at one minimum alveolar concentration, raising the possibility of altered anaesthetic potency. A review of the literature revealed a lack of evidence examining the pharmacodynamics of anaesthetic drugs in lipid-loaded patients. As the use of lipid emulsion increases, further research is required to guide safe and effective anaesthetic practice in this setting.

Maple Syrup Urine Disease (MSUD) is a rare autosomal recessive metabolic disorder characterised by defective branched-chain amino acid (BCAA) catabolism, leading to neurotoxicity, recurrent metabolic crises, and neurodevelopmental impairment. Evidence on long-term outcomes in paediatric cohorts, particularly with pharmacological adjuncts such as sodium phenylbutyrate (NaPBA) and radiological recovery, remains limited. We undertook a retrospective review of 13 paediatric patients with MSUD (69.2% classic phenotype, 30.8% intermittent) followed at a tertiary metabolic centre in Türkiye between 2003 and 2022. Demographic, biochemical, neurodevelopmental, neuroimaging, and genetic data were evaluated, with specific attention to dietary management, haemodialysis during acute decompensation, and NaPBA therapy. All patients exhibited neurodevelopmental delay, which was more pronounced in the classic phenotype. Milestone-level analysis demonstrated delays in walking (85%), sentence formation (92.3%), and toilet training (92.3%). One year after dietary intervention, mean plasma concentrations of leucine, isoleucine, and valine decreased by 60.9%, 55.9%, and 65.0%, respectively (p < 0.01). Haemodialysis during metabolic crises rapidly reduced leucine (- 73.8%) and ammonia (- 66%), though was more frequently required in patients with the classic phenotype. NaPBA treatment was associated with lower leucine levels during follow-up (p < 0.05). Baseline MRI abnormalities were identified in 87% of patients; 57% showed complete resolution post-treatment, with partial radiological improvement observed alongside clinical follow-up. A phenotype-specific approach combining early dietary intervention, timely haemodialysis in acute crises, and selective use of NaPBA may support metabolic stabilisation and radiological improvement in selected patients. Larger multicentre studies are warranted to validate these findings and refine management protocols.