Maple syrup urine disease (MSUD) is due to branched-chain alpha-ketoacid dehydrogenase (BCKAD) deficiency of the branched-chain amino acids (BCAAs leucine, isoleucine, and valine). Four forms are described. The early onset classic form manifests after birth, between three and four days of age, by lethargy, poor feeding and neurological signs of intoxication. Clinical course without treatment is characterized by deepening coma with maple syrup odor of urine. Subacute MSUD occurs later and manifests with encephalopathy, mental disability, major hypotonia, opisthotonus and cerebral atrophy with severe outcome. The intermittent form of MSUD may manifest at any age and presents with repeated ketoacidosis coma. Thiamine-responsive MSUD is a very rare form characterized by improvement of the biochemical profile with thiamine therapy. The disease is inherited in an autosomal recessive manner. Diagnosis is based on elevated plasma and urine concentrations of leucine, isoleucine and valine, and presence of allo-isoleucine, sometimes only during episodic decompensation in intermittent MSUD. Emergency treatment of the acute form rests on extracorporeal epuration (hemodialysis/hemofiltration) and nutritional therapy (high-calorie diet for life devoid of BCAAs). Any lapse of the diet can cause acute decompensation, which is sometimes fatal when intracranial hypertension and basal ganglia damage are associated. Long-term treatment includes diet strictly limited in BCAAs. Prenatal diagnosis is possible.