Objective:The purpose of the study is to gather natural history data to better understand the changing course of type 2 Gaucher disease (GD2) in order to guide future interventional protocols.Methods:A structured interview was conducted with parents of living or deceased patients with GD2. Retrospective information obtained included disease presentation, progression, medical and surgical history, medications, family history, management, complications, and cause of death, as well as the impact of disease on families.Results:Data from 23 patients were analyzed (20 deceased and 3 living), showing a mean age at death of 19.2 months, ranging from 3 - 55 months. Fourteen patients were treated with enzyme replacement therapy (ERT), 2 were treated with substrate reduction therapy (SRT) and 3 underwent bone marrow transplantation. Five patients received Ambroxol and one was on N-acetylcysteine, both considered experimental treatments. Fifteen patients had gastrostomy tubes (G-Tube) placed, while 10 underwent tracheostomies. Neurological disease manifestations included choking episodes, myoclonic jerks, autonomic dysfunction, apnea, seizures and diminished blinking, all of which worsened as disease progressed.Conclusions:Current available therapies appear to prolong life but do not alter neurological manifestations. Despite aggressive therapeutic interventions, GD2 still remains a progressive disorder with a devastating prognosis, that may benefit from new treatment approaches.

Purpose of review GBA1 mutations, which result in the lysosomal disorder Gaucher disease, are the most common known genetic risk factor for Parkinson disease and Dementia with Lewy Bodies (DLB). The pathogenesis of this association is not fully understood, but further elucidation of this link could lead to new therapeutic options. Recent findings The characteristic clinical phenotype of GBA1-PD resembles sporadic Parkinson disease, but with an earlier onset and more severe course. Many different GBA1 mutations increase the risk of Parkinson disease, some primarily detected in specific populations. Glucocerebrosidase deficiency appears to be associated with increased α-synuclein aggregation and accumulation, mitochondrial dysfunction because of impaired autophagy, and increased endoplasmic reticulum stress. Summary As our understanding of GBA1-associated Parkinson disease increases, new treatment opportunities emerge. MicroRNA profiles are providing examples of both up-regulated and down-regulated proteins related to GBA1 and may provide new therapeutic targets. Chaperone therapy, directed at either misfolded glucocerebrosidase or α-synuclein aggregation, is currently under development and there are several early clinical trials ongoing. Substrate reduction therapy, aimed at lowering the accumulation of metabolic by-products, especially glucosylsphingosine, is also being explored. Basic science insights from the rare disorder Gaucher disease are serving to catapult drug discovery for parkinsonism.