Insights into morbidity and mortality in Gaucher disease: a cohort study

Abstract

Background Gaucher disease (GD) is a rare lysosomal disorder classified, on the basis of neurological involvement, into type 1 (GD1, non-neuronopathic) and types 2 (GD2) and 3 (GD3) (neuronopathic). Data on morbidity and mortality in Latin American cohorts remain scarce. Aims To characterise morbidity and mortality patterns in a Brazilian GD cohort. Methods Retrospective cohort study at a single GD referral centre in Porto Alegre, Brazil (2003–2023; n = 53; GD1 = 45, GD2 = 4, GD3 = 4). Diagnosis was molecularly confirmed by Sanger and massive parallel sequencing of GBA1 . Comorbidities and causes of death were retrieved by chart review; survival was estimated by Kaplan–Meier analysis. Results: Median follow-up was 15 years. In GD1, comorbidities were predominantly psychiatric (71%), metabolic/endocrinological (69%) and cardiovascular (60%). Nine patients (17%) died: four GD1 patients (median age 65 years; three from malignancy, one from sepsis), all four GD2 patients (median age 5 months; respiratory or hepatic failure, sepsis) and one GD3 patient (Sudden Unexpected Death in Epilepsy at 27 years). Conclusions The phenotype-specific mortality pattern — malignancy as the leading cause of death in GD1, uniform early death in GD2 reflecting the disease's neurological trajectory rather than a failure of enzyme replacement therapy, and neurological death in GD3 — underscores the substantial burden of oncological, cardiovascular, metabolic and neurological comorbidities in this population and supports systematic multidisciplinary surveillance as a routine component of GD care in Brazil, even in resource-limited settings. Take-home message Adult patients with Gaucher disease type 1 require close clinical monitoring for oncological, cardiovascular, metabolic and psychiatric comorbidities. Gaucher disease type 2 remains a devastating disease with a poor prognosis under current therapies.