Cerebral edema in maple syrup urine disease despite newborn screening diagnosis and early initiation of treatment

Abstract

A 7-day-old girl had an elevated leucine level on newborn screen drawn at 2 days of age and was suspected of having maple syrup urine disease (MSUD). When reported, the patient was immediately admitted to hospital, and started on a modified diet involving high calories with reduced branched chain amino acid (BCAA) formula. Clinical exam was normal at initial assessment. Despite rapid initiation of treatment, the baby became lethargic and somnolent over the next day. Diet was stopped and infusions of 12.5% dextrose and 20% intravenous lipids at 2 g/kg per day were immediately started. Lethargy improved within 3 h of intravenous therapy initiation. Brain magnetic resonance imaging demonstrated diffuse cerebral edema, and symmetric restricted diffusion in bilateral cerebellar white matter, dorsal brainstem, thalami, globi pallidi, posterior limbs of internal capsules, and corona radiata. Plasma leucine was 1.98 mmol/L on admission (normal 0.05–0.17 mmol/L), decreasing to 1.34 mmol/L with diet, however clinical deterioration occurred despite improving leucine levels. Cerebral edema in MSUD is thought secondary to a combination of increased cerebral BCAA levels, and depleted levels of other essential amino acids, as well as neurotransmitters. Our case illustrates that newborns can develop encephalopathy with cerebral edema despite treatment with special formula initiated while asymptomatic. These findings suggest decompensation may begin early on, so that early introduction of high dextrose infusion and intravenous lipids, in combination with reduced BCAA formula, should be initiated for any patient with a positive newborn screen for MSUD.