NGLY1 Natural History

N-glycanase 1 (NGLY1) Deficiency (OMIM #615273) is an ultra-rare, autosomal recessive disorder caused by loss of function variants in NGLY1 gene. The multisystemic disorder is characterized by five key features: (1) global developmental delay and/or intellectual disability, (2) a (primarily) hyperkinetic movement disorder (3) transient elevation of liver transaminases (4) (hypo)- alacrima and (5) peripheral neuropathy. The condition was first reported in 2012 and thus comprehensive characterization of the disease, especially its unique movement disorder, continues to be described. The hyperkinetic movement disorder in NGLY1 Deficiency is highly complex and has been qualitatively described to include choreiform, athetoid, dystonic, myoclonic, action tremor, and dysmetric movements. These descriptors apply to both lower and upper limb movement in individuals with NGLY1 Deficiency. Preliminary results indicate that NGLY1 Deficiency is associated with a myriad of movement control problems and range from being unable to perform certain arm movements or walk to behaviors that appear quite similar to age-matched neurotypical individuals. Preliminary results suggest that when reaching for objects, arm motion patterns tend to display unusual joint and hand trajectories, relative to neurotypical individuals, thereby decreasing their effectiveness/efficiency. During gait, range of joint motion, particularly at the knee, was often significantly reduced combined with evidence of leg movement asymmetry. Additionally, preliminary results indicate that there is low frequency tremor, particularly in the upper limbs, that tends to decline during arm acceleration. These preliminary findings, if confirmed in a larger sample, provide entryways to the understanding of how NGLY1 Deficiency impacts movement control and thereby may serve both as diagnostic and therapeutic endpoints for physicians and therapists. The purpose of this natural history study in NGLY1 Deficiency is to collect