Long Term Follow-Up of 103 Untreated Adult Patients with Type 1 Gaucher Disease.

Dinur Dinur,Oppermann Oppermann,Zimran Zimran,Revel-Vilk Revel-Vilk,Hovakimyan Hovakimyan,Becker-Cohen Becker-Cohen,Arkadir Arkadir,Cozma Cozma,Demuth Demuth,Rolfs Rolfs

doi:10.3390/jcm8101662

Abstract

The introduction of disease-specific therapy for patients with type I Gaucher disease (GD1) was a revolution in the management of patients, but not without cost. Thus, the management of mildly affected patients is still debated. We herein report a long-term follow-up (median (range) of 20 (5–58) years) of 103 GD1 patients who have never received enzymatic or substrate reduction therapy. The median (range) platelet count and hemoglobin levels in last assessment of all but six patients who refused therapy (although recommended and approved) were 152 (56–408) × 103/mL and 13.1 (7.6–16.8) g/dL, respectively. Most patients had mild hepatosplenomegaly. Nine patients were splenectomized. No patient developed clinical bone disease. The median (range) lyso-Gb1 levels at last visit was 108.5 (8.1–711) ng/mL; lowest for patients with R496H/other and highest for patients refusing therapy. This rather large cohort with long follow-up confirms that mildly affected patients may remain stable for many years without GD-specific therapy. The challenge for the future, when newborn screening may detect all patients, is to be able to predict which of the early diagnosed patients is at risk for disease-related complications and therefore for early treatment, and who may remain asymptomatic or minimally affected with no need for disease-specific therapy.

Highlights

Gaucher disease (GD), one of the most common lysosomal storage disorders, is a multi-system disease known for its great phenotypic heterogeneity [1,2]The disease is characterized by hepatosplenomegaly, anemia, thrombocytopenia, and skeletal disease
The clinical charts of 440 adult patients (>23 years at time of last evaluation) with GD1 followed in Shaare Zedek Medical Center who were followed for more than five years and evaluated at least once between July 2014 to February 2019 were reviewed (Figure 1)
One hundred and three untreated patients with GD1 followed for a median of 22 (5–58) years were included in the study

Summary

Introduction

Gaucher disease (GD), one of the most common lysosomal storage disorders, is a multi-system disease known for its great phenotypic heterogeneity [1,2]The disease is characterized by hepatosplenomegaly, anemia, thrombocytopenia, and skeletal disease. Enzyme replacement therapy (ERT) for patients with type 1 GD (GD1), first introduced in 1991 [3], has proven to be effective in the management of the key disease parameters and preventions of bone-related complications [4]. Oral substrate reduction therapy (SRT ) has been introduced for the treatment of GD1 in 2000 with miglustat and in 2014 with eliglustat [6,7]. This therapy aims to prevent storage not by correcting the original enzymatic defect but, instead, by decreasing the biosynthesis of the glucocerebroside, resulting in less or no accumulating of the substrate. Reviews about GD as well as chapters in textbooks fail to emphasize the fact that many patients may remain untreated for many years without any GD-related complications [10]

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