Neurocognitive Outcomes and Quality of Life in Adults with MSUD

Dr. Jessica Gold

Children’s Hospital of Philadelphia

Successful transition to independent adulthood requires intact executive and
adaptive function. These neurocognitive domains are frequently impaired in
inherited metabolic disorders (IMD), despite optimal management. For many
IMDs, the impact of executive and adaptive dysfunction on long-term out
comes remains undefined. Standardized assessments linking neurocognitive
status with functional outcomes are needed to improve prognostication and
tailor support for affected emerging adults. Maple syrup urine disease
(MSUD), a relatively prevalent IMD, is primarily diagnosed in the first week of
life through newborn screening. Despite early intervention, executive and
adaptive dysfunction persist. We designed a remote, interactive battery of neu
rocognitive and functional assessments for adults (≥21 years) with MSUD to
correlate neurocognition and long-term outcomes. Participants were selectively
recruited for racial, ethnic, socio-economic, and geographic diversity. Assess
ments completed by 28 adults with MSUD (82% diagnosed after symptom
onset, 25% from minority communities) show a wide range in educational
attainment, employment, and residence. Executive and adaptive function were
significantly impaired in adults with MSUD compared to controls. Executive
and adaptive deficits correlated negatively with educational attainment,
employment, and obtaining skills needed for adult-oriented healthcare or inde
pendent living. Clinical history did not predict functional outcomes, but neuro
cognitive assessments suggest the benefits of pre-symptomatic diagnosis.
Independent adulthood is attainable for individuals with MSUD. Routine
assessment of neurocognition and interventions targeting executive and adap
tive function may improve long-term functional outcomes in IMD.

This project was supported by the Million Dollar Bike Ride, sponsored by the Orphan Disease Center at the University of Pennsylvania.