A young girl with recurrent episodes of CNS demyelination associated with defective mitochondrial beta oxidation is reported from the Departments of Pediatrics, Medical Genetics, Oregon Health Sciences University, Portland, and University of Iowa Hospitals, Iowa City, IA. The child was well until age 14 months when she began having episodes of ataxia with slurred speech and extreme irritability lasting hours to days. At 19 months she was admitted in coma and a CT revealed periventricular loss of white matter. She recovered within three weeks after treatment with immunoglobulins, Acyclovir, and corticosteroids. A similar episode occurred at 22 months of age and the MRI had increased signals in the periventricular and frontoparietal areas. Many episodes of ataxia, slurred speech, painful bright red hands and feet, furrowed tongue and extreme irritability occurred from age 22 to 38 months. The episodes lasted from hours to weeks and were associated with an acrid body odor. Urinary sarcosine was elevated and an increase in ethylmalonic acid in the urine pointed to a disorder affecting fatty acid metabolism. Metabolic evaluations and decreased oxidation of palmitate demonstrated defective mitochondrial beta oxidation. The patient was treated and remained stable for 30 months on a low fat high carbohydrate diet, L-Carnitine (100 mg/kg/d), and Riboflavin (20 mg/kg/d). [1]