Clinicogenetic Profile, Treatment Modalities, and Mortality Predictors of Gaucher Disease: A 15-Year Retrospective Study

Public Health Genomics 2021 Apr 6;1-10. doi: 10.1159/000514507.

PMID: 33823526

Anitha M Barney , Sumita Danda , Aby Abraham

Highlights: If left untreated, Gaucher disease is a rare disease with a high mortality rate. Due to its one-time intervention and low cost, HSCT may be a more appropriate definitive treatment option in resource-constrained areas like India, where the neuronopathic form is more prevalent, assuming similar efficacy to ERT. 

Abstract

Introduction: Gaucher disease (GD) is a rare autosomal recessive lysosomal storage disorder in which biallelic pathogenic variants in the Glucosidase beta acid (GBA) gene cause defective glucosylceramidase function, resulting in glucocerebroside deposition in cells. There are three major types of GD: non-neuronopathic (type I), acute neuronopathic (type II), and chronic neuronopathic (type III). There are few and expensive definitive treatment options. If left untreated, they succumb to the disease at a young age. There is a scarcity of studies from the Indian subcontinent that elicit the factors that lead to their premature death.

Materials and methods: From 2004 to 2019, researchers conducted a retrospective study in a tertiary care setting in South India to assess the clinical profile, mutation spectrum, various management strategies (only supportive therapy, enzyme replacement therapy [ERT], substrate reduction therapy [SRT], haematopoietic stem cell transplant [HSCT]), and mortality predictors of patients with GD. The survival curve was produced using the Kaplan-Meier method. For novel variants, in silico predictions were performed.

Results: During the 15-year study period, 60 individuals with all types of GD were observed. Their median age at the time of diagnosis was two years. The average duration of follow-up was 5 years (interquartile range [IQR] = 2-8). The overall mortality rate was 35%; however, only 10% of those who received definitive therapy died. Mortality rate was higher (47.5%) by more than 4 folds in those only on supportive therapy. The definitive treatment group had a median survival of 6.3 years (IQR = 3.5-10.8) while the supportive therapy group had a median survival of 3.5 years (IQR = 1-5) from the time of diagnosis. According to the Kaplan-Meier survival analysis, we observed a significant difference in mortality between these groups (p value 0.001). The neuronopathic type (OR = 5) and only supportive treatment (OR = 6.3) were revealed to be independent risk factors for premature mortality in the multiple logistic regression analysis.

Conclusion: If left untreated, GD is a rare disease with a high mortality rate. The definitive therapies that improve survival include ERT and SRT. Due to its one-time intervention and low cost, HSCT may be a more appropriate definitive treatment option in resource-constrained areas like India, where the neuronopathic form is more prevalent, assuming similar efficacy to ERT. However, the efficacy and safety of HSCT in GD must be confirmed by large numbers of patients receiving the procedure.

Keywords: Enzyme replacement therapy, Glucosyl ceramidase Beta gene, Haematopoietic stem cell transplantation, Mortality predictors