PC2177: Intermittent Maple Syrup Urine Disease: A Surreptitious Diagnosis

Introduction: Maple syrup urine disease (MSUD) is a rare autosomal recessive deficiency of the branched-chain alpha-keto acid dehydrogenase enzyme that causes disordered metabolism and accumulation of branched-chain amino acids. Varied percentage of enzyme deficiency results in five phenotypes with classic and intermittent MSUD being the most common. While classic often presents in the neonatal period, intermittent MSUD presents as recurrent episodes of encephalopathy and ataxia and may not be captured on routine newborn screening. We present a case of intermittent MSUD with prolonged time to diagnosis due to brief, self-resolving episodes.

Case Description: A 19 month old Caucasian female with history of mild gross motor and expressive language delays presented to the emergency department after recurrent episodes of acute alternating hemiparesis, truncal instability, and irritability. There were five total episodes over four months with care received at multiple health care facilities. Episodes lasted several hours and resolved without intervention. Patient returned to baseline after each episode, prior to receiving medical attention. EEG was normal after the second episode, and newborn screening had also been normal. Some episodes were preceded by mild viral symptoms or increased activity.

During the fifth episode, parents were able to record video demonstrating right-sided weakness, difficulty walking, head-tilt, and truncal ataxia. A non-urgent sedated MRI showed symmetric abnormal signal of the basal ganglia, brain stem, deep cerebellar nuclei, and anterior temporal white matter, most concerning for a metabolic disorder.

Plasma amino acids, urine organic acids, and CSF amino acids showed elevations of valine, leucine, isoleucine, and alloisoleucine consistent with a diagnosis of intermittent MSUD. Genetic testing revealed one copy of a known pathogenic variant (c.509G>A (p.Arg170His)) and another copy of a variant of uncertain significance (c.302G>A (p.Gly101Asp)) for the gene coding for BCKDHB (branched-chain ketoacid dehydrogenase E1-beta subunit). Patient was started on an appropriate protein-restricted diet managed by a metabolic genetics team.

Discussion: Our patient’s presentation demonstrates the difficulty of diagnosis in patients with subtle findings, especially when symptoms resolve quickly and are communicated to different providers without continuity of care. The use of home video as an information-gathering tool was a key turning point in the evaluation for this patient; it clarified symptoms previously described by parents and prompted MRI and subsequent metabolic and genetic workup.

Conclusion: Considering that patients with intermittent MSUD are still at risk for acute metabolic decompensation, irreversible neurological damage and even death, it is important to consider metabolic disorders even with mild intermittent symptoms. Home videos and detailed symptom diaries can assist in identifying atypical presentations of metabolic disease within the primary care setting, and help to initiate biochemical testing to make an early and life-altering diagnosis.