Gaucher disease (GD) is a rare, autosomal recessive inborn error of metabolism caused by deficient acid β-glucosidase activity. Its major substrate, glucosylceramide, accumulates within lysosomes of tissue macrophages in multiple organs. Three phenotypes are traditionally identified: type 1 (non-neuronopathic), type 2 (acute neuronopathic) inevitably fatal early in life, and type 3 (chronic neuronopathic) with heterogeneity in CNS manifestations, severe systemic disease, and death usually during adolescence or before. GD type 1 (GD1) is characterized by the absence of overt, early-onset neurological signs and symptoms. However, neurological conditions such as peripheral neuropathy and Parkinson's disease may occur in GD1. Disease manifestations for GD1 are multisystemic and include splenomegaly, hepatomegaly, anemia, thrombocytopenia, and skeletal pathology including chronic bone pain, acute bone crises, episodic osteonecrosis with joint destruction, and bone mineral loss with high fracture risk [1]. Prior to introduction of placental-derived glucocerebrosidase (alglucerase) enzyme replenishment therapy (ERT), apart from some individuals of Ashkenazi Jewish ancestry with a low penetrant phenotype, GD1 was generally stochastically progressive and associated with substantial morbidity, diminished quality of life, and shortened life expectancy [2]. In the only clinical trial prior to approval, intravenous alglucerase alleviated symptoms of anemia and marked splenomegaly in 12 severely affected children and adults some of whom relapsed rapidly when ERT was interrupted [3]. Due to a pressing need and lack of an alternative, alglucerase was approved by FDA for clinical use subject to agreement by the manufacturer, Genzyme Corporation, to conduct a post-marketing follow-up study to confirm efficacy and to detect any safety concerns. The Genzyme sponsored International Collaborative Gaucher Group (ICGG) Gaucher Registry (NCT00358943) was launched in 1991 as an observational, longitudinal, international database of clinical, biochemical, and therapeutic characteristics of patients with GD of all phenotypes regardless of disease severity, treatment status, or treatment choice. The Registry recently marked its 32nd anniversary. Genzyme was purchased by Sanofi SA in 2011. Alglucerase has been replaced by recombinant ERTs (imiglucerase, velaglucerase alfa, taliglucerase alfa). Oral small molecule inhibitors of glucosylceramide synthase (substrate restriction therapy, SRT) are alternative effective treatments for eligible GD1 patients. The ICGG Registry collects data for all these treatments as well as for patients who are not currently being treated either due to mild phenotypes or patient choice [1].

The history and accomplishments of the ICCG Registry were extensively reviewed in 2015 and in 2022 [4,5]. As little has changed since those publications, I will reiterate their most salient findings followed by a personal historical perspective on how a now chronologically mature but young at heart Registry has impacted its patients, its medical community, and other GD stakeholders.