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

Abstract

<b><i>Introduction:</i></b> Gaucher disease (GD) is a rare autosomal recessive lysosomal storage disorder, in which biallelic pathogenic variants in the Glucosidase beta acid (<i>GBA</i>) gene result in defective functioning of glucosylceramidase that causes deposition of glucocerebroside in cells. GD has 3 major types namely, non-neuronopathic (type I), acute neuronopathic (type II), and chronic neuronopathic (type III). Definite treatment options are limited and expensive. They succumb early to the disease, if untreated. There is paucity of studies from the Indian subcontinent, which elicit the factors resulting in their premature mortality. <b><i>Materials and Methods:</i></b> A retrospective study was carried out in a tertiary care setting of South India to assess the clinical profile, mutation spectrum, and 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 from 2004 to 2019. A Kaplan-Meier survival curve was plotted. In silico predictions were performed for novel variants. <b><i>Results:</i></b> There were 60 patients with all types of GD seen over the study period of 15 years. Their median age at diagnosis was 2 years. The median follow-up was for 5 years (interquartile range [IQR] = 2–8). The overall mortality rate was 35%; however, it was only 10% in those receiving definite treatment. Mortality was higher (47.5%) by more than 4 folds in those only on supportive therapy. The median survival from the time of diagnosis was 6.3 years (IQR = 3.5–10.8) in the definite treatment group and 3.5 years (IQR = 1–5) in those on supportive therapy. The Kaplan-Meier survival analysis showed significant (<i>p</i> value 0.001) mortality difference between these groups. The multiple logistic regression analysis found the neuronopathic type (OR = 5) and only supportive therapy (OR = 6.3) to be the independent risk factors for premature mortality. <b><i>Conclusion:</i></b> GD is a rare disease with a high mortality rate, if left untreated. ERT and SRT are the definitive treatments which increase the survival. In resource-limited settings like India, with higher prevalence of the neuronopathic type, HSCT may be a more suitable definitive treatment option, due to its one-time intervention and cost, assuming similar efficacy to ERT. However, the efficacy and safety of HSCT in GD needs to be established further by substantial patient numbers undergoing it.

Gaucher disease: clinical phenotypes and refining GBA mutational spectrum in Thai patients

“…Our result suggested that mutation spectrum of GBA in Thai patients was more homogeneous than ever believed and was different from those seen in Caucasian populations, and more similar to those of East Asian descendants [ 4 , 6 , 11 , 13 , 15 – 17 , 22 ].…”

Gaucher disease: clinical phenotypes and refining GBA mutational spectrum in Thai patients

“…Our result suggested that mutation spectrum of GBA in Thai patients was more homogeneous than ever believed and was different from those seen in Caucasian populations, and more similar to those of East Asian descendants [3,5,10,12,[16][17][18]21].…”

Women with Gaucher Disease

“…In this context, treatment with iron supplementation and, in some cases, an antifibrinolytic agent, may be necessary. Treatment with oral contraceptives is considered a good therapeutic option for young patients with menorrhagia [ 4 ]. Increased menstrual bleeding associated with intrauterine devices (IUDs) has been reported in up to 50% of patients, especially if associated with severe disease [ 9 ].…”

“…In contrast, eliglustat is a first-line treatment, like ERT, and is applicable to all patients with GD1 who are not ultra-rapid metabolizers of cytochrome CYP2D6 [ 3 ]. These treatments have increased the survival and the quality of life of the patients [ 4 ].…”