Supplementary Material for: Symptomatic Benefit of Acetyl-DL-Leucine for Cerebellar Ataxia in Juvenile Tay-Sachs Disease: A Pediatric Case and Literature Review

Introduction: Juvenile Tay-Sachs disease (TSD) is a GM2 gangliosidosis that commonly progresses with cerebellar ataxia, while evidence for symptomatic therapies remains limited. Acetyl-leucine has shown short-term benefit for ataxia in several lysosomal storage disorders, but pediatric data in GM2 gangliosidosis are scarce. We report a child with juvenile TSD treated off-label with racemic acetyl-DL-leucine (ADLL) and review the related literature.
Case presentation: A six-year-old girl with previously normal early development was referred for autism spectrum features and a strong family history of metabolic disease. During follow-up she developed seizures and neurodevelopmental regression, and juvenile TSD was diagnosed by molecular analysis and confirmed by enzymatic testing. Progressive cerebellar ataxia subsequently developed, and ADLL was initiated off-label for symptomatic treatment. After six months, ataxia improved clinically, with the Scale for the Assessment and Rating of Ataxia score decreasing from 29 to 25. The family reported better gait stability and increased participation in daily life, and no adverse effects were reported.
Conclusion: Consistent with emerging data in GM2 gangliosidoses and other lysosomal storage disorders, this case supports the use of ADLL as a potential symptomatic treatment for progressive cerebellar ataxia in juvenile TSD. ADLL was well tolerated and was associated with clinically meaningful improvements in gait, daily participation, and ataxia scores. These findings add pediatric support to the growing evidence that ADLL may be used safely as symptomatic therapy in TSD-related ataxia.