Sandhoff Disease: Improvement of Gait by Acetyl-DL-Leucine: A Case Report
An 8-year-old boy suffered from genetically proven juvenile-onset GM2-gangliosidosis, Sandhoff disease (in HEXB: c.[758delA] + [763A > C]; p.[E253GfsX2] + [S255R]). Before treatment, he could not even stand unassisted ([Video 1]). As it has been shown that the modified amino acid acetyl-DL-leucine (AL) improves symptoms in a different lysosomal storage disease (LSD), Niemann–Pick disease type C,  he was treated with 0.1 g/kg/day as an “individual case of off-label use.” After 6 months of treatment, he was able to walk unassisted (video). There was also an improvement of the Scale for the Assessment and Rating of Ataxia (SARA) from 36 of 40 to 32 of 40 and of the 8-m-walk test from 18.1 seconds “only with strong support” to 13.8 seconds “without support.” AL was well tolerated. When it was transiently discontinued, within 2 weeks his condition was the same as before treatment. Since this always happened, he is still on AL, as he has been since 2017 (additional medications: lacosamide, pregabalin, and miglustat).
Video 1 Before treatment, this 8-year-old boy with Sandhoff's disease could not stand or walk unaided (“baseline”). Six months after initiation of treatment with acetyl-DL-leucine (0.1 g/kg per day), he was able to walk on his own, even across a soccer field (“on medication”).
The acute effects might be explained by one mode of action of AL; it normalizes membrane potential and may thereby “revitalize” neuronal networks. Based on our clinical findings, back-translational research was performed in an animal model of Sandhoff's disease (Hexb −/−): AL, in the same oral dosage/kg/day, led to an improvement of motor function, a significant increase in life span, and reduced glycosphingolipid storage in the forebrain and cerebellum. AL also normalized altered glucose and glutamate metabolism and increased autophagy and superoxide dismutase. These preclinical studies support our clinical findings and elucidate the multiple modes of action of AL in LSD ([Video 1]).
Received: 02 April 2020
Accepted: 19 April 2020
06 September 2020 (online)
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