Jack Green, MD
Pediatric Intensivist / Assistant Professor of Pediatrics
Cedars-Sinai Medical Center
West Hollywood, California, United States
Disclosure information not submitted.
Title: Late-onset Maple Syrup Urine Disease triggered by HHV-6 mediated toxic-metabolic encephalopathy
Case Report Body:
Introduction: Maple Syrup Urine Disease (MSUD) is an autosomal recessive genetic disorder caused by an enzyme deficiency that leads to toxic buildup of the branched-chain amino acids leucine, isoleucine, and valine. Classically diagnosed in the neonatal period (especially with the advent of newborn screening), babies present with symptoms of lethargy, poor feeding, and progressive neurologic findings. Here we present a rare case of a previously healthy toddler with seizures and encephalopathy ultimately diagnosed with late-onset or intermittent MSUD.
Description: A 16-month-old female with a history of mild gross motor delay presented to the ED with 1 day of altered mental status and decreased oral intake. Ten days prior, she experienced an episode of unsteady gait which led to a fall. Otherwise, parents denied recent illnesses, ingestions, or sick contacts. In the ED, she was found to have right gaze deviation with right upper extremity stiffening for several minutes. Lorazepam was given and a stat brain CT was normal. Labs revealed hypoglycemia (52 mg/dL), metabolic acidosis (16 mmol/L) with increased anion gap (24 meq/L), and urinalysis showing 2+ ketonuria. LP showed no leukocytosis with CSF glucose 32 mg/dL and CSF protein 16 mg/dL. Broad-spectrum anti-infectives were initiated. MRI brain then followed which showed increased signal in the globus pallidus extending into the internal capsule, in the posterior midbrain, and in the tracts extending into the pons/medulla. She was initially managed with anti-epileptic drugs to control seizure-like posturing but no ictal correlate on EEG. She continued to deteriorate requiring intubation. HHV-6 was noted to be positive in the CSF. She was eventually transferred out for subspecialty metabolic care, where MR Spectroscopy and serum amino acid assay clinched the diagnosis of MSUD. Initial plasma leucine level was 2499 umol/L (range < 180). She underwent dialysis for leucine-mediated CNS toxicity. After a 2-week hospitalization, she was back to her neurologic baseline.
Discussion: Metabolic crisis should always be on the differential diagnosis of a toddler presenting with focal neurologic signs and refractory ketoacidosis. Though MSUD diagnosis is incredibly rare beyond the neonatal period, prompt recognition and treatment can be life-saving and lead to good outcomes.