Gaucher Disease in Ontario, Canada: Clinical Manifestations, Natural Progression, and Treatment Response

Abstract

Gaucher disease (GD) is characterized by a deficiency in lysosomal glucocerebrosidase, resulting in a multisystemic disease with substantial variability in clinical manifestations, disease progression, and treatment response. This is the first study in Canada that examines the epidemiological profile of Gaucher patients, mapping out the GD clinical spectrum in the ethnically diverse province of Ontario.Study found a prevalence of 1:155,367 (1:9,853 for Ashkenazi-Jews) type 1 GD adults in Ontario. Splenectomy was associated with improved thrombocytopenia, worsened hyperferritinemia and bone pain, but no effects on anemia, bone mineral density or bone crises. Compared to the non-treatment group, a higher proportion of patients who received enzyme replacement/ substrate reduction therapy (ERT/SRT) presented with anemia, hepatomegaly, bone pain, and bone crises at baseline, suggesting that these presentations may be predictive of subsequent need for treatment. ERT/SRT were effective in improving all hematological, visceral, and skeletal manifestations (except bone mineral density), whereas the non-treatment group remained clinically stable over time (10.88 years) without significant disease progression -thus early use of ERT/SRT may not be necessary in all patients. This comprehensive analysis summarizes the genotypic and phenotypic heterogeneity of GD, serving as a comparative resource for optimization of care for adult patients.

A Cross-Sectional Retrospective Study of Non-Splenectomized and Never-Treated Patients with Type 1 Gaucher Disease

“…Overall, laboratory parameters did not change over time, except hemoglobin concentration that improved, differently from what was reported by Chi and Amato [18]. The stability of platelet count and GD1 biomarkers was previously observed [12,15,18]. Moreover, we confirmed in a more genotypically heterogeneous population the negative correlation between glucosylsphingosine level and platelet count previously reported by Dinur et al Eight patients (22%) filled the criteria for treatment initiation at the last evaluation, and two of them (5.5%) already at diagnosis.…”

“…Fatigue in GD1 is not exclusively explained by hematological alterations, such as anemia, and other causes should be explored [27]. Overall, laboratory parameters did not change over time, except hemoglobin concentration that improved, differently from what was reported by Chi and Amato [18]. The stability of platelet count and GD1 biomarkers was previously observed [12,15,18].…”

“…GD1 was the first lysosomal storage disorder to be treated by ERT. Although the impact on life expectancy remains difficult to demonstrate due to the lack of an equivalent comparative group of untreated patients, ERT has dramatically modified the patients' outcomes [18,23,24]. For some patients with poorly symptomatic disease, ERT benefit might appear negligible relative to its cost, and they are often not treated.…”

“…Therefore, better understanding the natural disease course in this subgroup of patients with GD1 is essential. Previous studies analyzed the natural course of untreated patients with GD1 [ 9 , 11 , 12 , 13 , 14 , 16 , 17 , 18 , 19 ]. All these studies included splenectomized patients.…”

“…It is also important to gather more knowledge on the long-term disease course in never-treated patients with less aggressive GD, to better adapt their management. However, very few and often contradictory data are available in the literature on the natural course of untreated patients with GD [ 9 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ]. Most studies are retrospective, with heterogeneous cohorts and fragmented data, and have also included splenectomized patients.…”