Maple syrup urine disease (MSUD) is a rare autosomal recessive metabolic disorder caused by a deficiency in the branched-chain α-keto acid dehydrogenase (BCKD) complex, which impairs the catabolism of branched-chain amino acids (BCAAs): leucine, isoleucine, and valine. The resulting accumulation of these amino acids and their corresponding ketoacids leads to neurotoxicity and systemic metabolic derangements. MSUD typically presents in the neonatal period with poor feeding, vomiting, lethargy, dystonia, and seizures, often progressing to encephalopathy and coma if untreated. A hallmark feature is the characteristic sweet odor of the urine, reminiscent of maple syrup. MSUD is classified into five phenotypes: classic, intermediate, intermittent, thiamine-responsive, and E3-deficient, with the classic form being the most severe and common. Diagnosis is confirmed through plasma amino acid analysis, revealing elevated BCAAs and the presence of allo-isoleucine, supported by genetic testing of BCKDHA, BCKDHB, or DBT mutations. Neuroimaging may show intramyelinic and vasogenic edema, particularly in myelinated regions of the brainstem and cerebellum. Management involves dietary restriction of BCAAs, supplementation with BCAA-free medical formulas, and aggressive treatment of metabolic crises using intravenous glucose, insulin, and, in severe cases, hemodialysis. Liver transplantation offers a curative option by restoring BCKD activity. Early diagnosis via newborn screening and prompt intervention are critical for preventing irreversible neurological damage and improving long-term outcomes.