Case Presentation: A 23 year-old man with history of classic maple syrup urine disease (MSUD) and obesity presented with chief complaint of 3 days of vivid nightmares and hallucinations. He denied abdominal pain, vomiting, imbalance, or other neurologic symptoms. He did report increased life stressors (college coursework) in the week prior to his symptom onset, while he denied deviating from his MSUD diet. Patient was on ‘MSUD Cooler’ supplements with isoleucine and valine, 7 pouches daily, no other medications. Vital signs: temperature 36.8 degrees C, pulse 93, respirations 20, blood pressure 137/93. Exam on admission was unremarkable- with normal cardiac, abdominal, and neurologic exam. Pediatric Genetics was consulted (our facility’s in-house MSUD experts) and they recommended obtaining stat plasma amino acids for send-out, but beginning empiric treatment and monitoring for leucine encephalopathy immediately since amino acid results would not be available for 24-36 hours. Treatment consisted of the following protocol: 10% dextrose in normal saline administered by IV at 200 ml/hr, monitor hourly serum glucose with goal glucose 100-180 mg/dl, use IV insulin drip or PRN IV glucose for values above or below that range, IV lipids at 25 ml/hr, no protein diet for 24 hours, low protein diet after 24 hours, twice daily basic metabolic panel (BMP), urine ketones with every urination, serum beta-hydroxybutyrate every 2 hours, neurologic checks every 2 hours, and continue home MSUD Cooler supplement. Serum beta-hydroxybutyrate and urine ketones remained within normal limits throughout hospitalization, as did his complete blood count and BMP. Criteria for discharge per Pediatric Genetics were plasma leucine in the normal range and resolution of symptoms. Admission plasma amino acid levels, resulted at 36 hours, are shown in Table 1. With treatment, patient’s leucine value dropped from 463 nmol/ml on admission, to 353 at 24 hours, 205 at 48 hours, and 72 at 72 hours (back to normal range). Patient’s nightmares and hallucinations did not recur once inpatient treatment was started. Patient was discharged home, at his baseline, after 72 hours of inpatient care.
Discussion: Maple syrup urine disease is an inborn error of metabolism, stemming from the absence of the enzyme that catalyzes decarboxylation of the branched chain amino acids (BCAAs)- leucine, isoleucine, and valine. Presence of ketones in the urine can mimic the smell of maple syrup and gives this disease its name. It occurs in approximately 1/185,000 life births. It is generally diagnosed in childhood either through newborn screening or through recognition of symptoms (encephalopathy and ketoacidosis). If untreated, accumulated BCAAs can cause neurotoxic effects including cerebral edema, brain herniation, and death. It is treated chronically via restricted intake of BCAAs with formulas and medical food, and acutely (metabolic decompensation) with glucose infusion and temporary complete protein restriction. Increased stressors, medical illness, and dietary indiscretion are common causes of metabolic decompensation in children and adults.
Conclusions: MSUD is very rare and most adult hospitalist’s experience with it is minimal. In cases of patients with MSUD with neurologic symptoms suggesting leucine intoxication, expert consultation and immediate therapy are essential to prevent permanent neurologic injury and death.