A 4-day-old, full-term male was born by vaginal delivery to a mother with no significant medical history. There were no complications during pregnancy or with delivery. The baby was discharged from the newborn nursery on day 2 of life. The patient had newborn screening performed at 25 hours of life and before discharge. After discharge, he fed well with no specific concerns. Starting on day 4 of life, his mother noted he was slowing with feeds and had been producing less urine. He also seemed more irritable, but not lethargic.

Newborn screening results were reported on day 4 of life and raised high concern for an inborn error of metabolism (IEM), prompting referral to the pediatric emergency room for further evaluation. In the emergency room, the patient was febrile and generally alert but with a weak cry; there was concern for dehydration. His limbs were hypertonic and his urine was noted to be cloudy.

Newborn screening from day 1 of life demonstrated elevated leucine at 574.74 uM and elevated valine at 438.15 uM, concerning for maple syrup urine disease (MSUD).

A full sepsis workup was initiated. Urine culture was positive for Enterococcus. Blood and CSF cultures were negative. The patient was also found to have an increased anion gap metabolic acidosis (anion gap 37, bicarbonate of 10). He had 4+ ketonuria. Serum beta-hydroxybutyrate was 4.98. Sodium was elevated to 152. He was hypoglycemic with a blood glucose of 33 mg/dl. The patient was started on IV ampicillin and gentamicin. Breastfeeds were immediately discontinued, and IV D12.5 + ½ normal saline at 1.5 X maintenance IV rate was initiated. A nasogastric tube was placed and Ketonex formula (deficient in branched-chain amino acids leucine, valine, and isoleucine) was initiated alongside valine and isoleucine supplementation. The patient was also started on IV thiamine supplementation.

Plasma amino acids at day 4 of life upon arrival to the hospital demonstrated dramatically elevated leucine to 2599 umol/L, with commensurate elevations in isoleucine and valine. Hemodialysis was initiated. Urine organic acids showed marked excretion of branched-chain ketoacids 2-ketoisocaproic, 2-keto-3-methylvaleric, 2-ketoisovaleric, and 2-hydroxyisovaleric acids. CSF amino acids also demonstrated marked elevations in branched-chain amino acids.

Brain MRI demonstrated T2 hyperintensity with diffusion restriction affecting actively myelinating structures (perirolandic white matter, posterior segments of internal capsules, corticospinal tracts, cerebellar white matter ( Fig. 34.1A – E ). Magnetic resonance spectroscopy showed branched-chain ketoacid peak at 0.9 ppm ( Fig. 34.1F ).

Maple syrup urine disease. Brain MRI, (A) axial T2 demonstrates brainstem hyperintensity due to intramyelinic edema ( arrow ). (B–E) DWI shows diffusion restriction in bilateral corticospinal tracts, deep gray matter, brainstem, and cerebellum ( arrowheads ). (F) MRS shows branched-chain ketoacid peak at 0.9 ppm ( asterisk ). DWI , Diffusion-weighted imaging; MRS , magnetic resonance spectroscopy.

Confirmatory genetic testing revealed compound heterozygous pathogenic variants in the BCKDHA gene consistent with classical MSUD. The patient was ultimately taken off hemodialysis within 24 hours and stabilized on an appropriate diet restricted in branched-chain amino acids.