Naturally occurring lysosomal storage disease consistent with neuronal ceroid lipofuscinosis in a group of 5 related captive rhesus macaques (Macaca mulatta).

Lysosomal storage diseases (LSDs) are a diverse group of inherited disorders characterized by the accumulation of undegraded macromolecules within lysosomes, leading to cellular dysfunction and progressive organ damage. Neuronal ceroid lipofuscinosis (NCL) is a subset of LSDs defined by the accumulation of autofluorescent lipopigments in neurons and, in some cases, peripheral tissues. While naturally occurring LSDs have been documented in domestic and laboratory species, reports in nonhuman primates (NHPs) remain rare. This study describes an LSD in 5 related rhesus macaques (Macaca mulatta) at the California National Primate Research Center, with clinical and histopathologic features supportive of NCL. Affected animals exhibited progressive cognitive and motor deficits, along with an atypical musculoskeletal phenotype including coarse facial features. Histologic examination revealed neuronal cytoplasmic vacuolation, primarily in the cerebellum and brainstem, with storage material exhibiting autofluorescence, positive staining with Sudan black, and luxol fast blue, and a positive periodic acid-Schiff reaction. Transmission electron microscopy identified structures resembling curvilinear inclusions and granular osmiophilic deposits, supporting a NCL diagnosis. This report expands the spectrum of NCL presentations in NHPs, reinforcing their potential as an alternative model for LSD research. The identification of this naturally occurring NCL model in NHPs may enhance our understanding of translational models for therapeutic strategies.