Recurrent de novo SPTLC2 variant causes childhood-onset amyotrophic lateral sclerosis (ALS) by excess sphingolipid synthesis.
Safoora B SyedaMuseer A LonePayam MohasselSandra DonkervoortPinki MunotMarcondes Cavalcante de França JuniorJuan Eli Galarza-BritoMatthias EckenweilerAlexander AsamoahKenneth GableAnirban MajumdarAnke SchumannSita D GuptaArpita LakhotiaPerry B ShiehA Reghan FoleyKelly E JacksonKatherine R ChaoThomas L WinderFrancesco CatapanoLucy FengJanbernd KirschnerFrancesco MuntoniTeresa M DunnThorsten HornemannCarsten G BönnemannPublished in: Journal of neurology, neurosurgery, and psychiatry (2023)
is the second SPT-associated gene that underlies monogenic, juvenile ALS and further establishes alterations of sphingolipid metabolism in motor neuron disease pathogenesis. Our findings also have important therapeutic implications: serine supplementation must be avoided in SPT-associated ALS, as it is expected to drive pathogenesis further.