Egyptian Gaucher disease type 3 patients: a large cohort study spanning two decades

Abstract

BackgroundGaucher disease (GD) has been the subject of genotype/phenotype studies as well as therapeutic innovation. A cohort of ethnically homogeneous Egyptian patients suffering from GD type 3 (GD3) is described here, with the effects of enzyme replacement therapy (ERT) highlighted.MethodsWe studied the long-term outcome after 20 years of ERT in 85 patients with GD3 registered at the Pediatric Hematology Clinic of Cairo University since 1998. We obtained organ volumes, growth parameters, and neurological assessment at baseline and during ERT.ResultsOf the total sample, 77.6% of patients were diagnosed before the age of 2 years. Our patients were highly consanguineous, and 51% had a family history of GD. The most prevalent genotype was homozygous p.Leu483Pro (75.7%), followed by homozygous p.Asp448His (11%). Hemato-visceral aspects of disease included anemia (75.6%), moderate to severe thrombocytopenia (21.7%), severe splenomegaly (49.2%), and severe hepatomegaly (10.8%). One patient had liver cirrhosis with hepatopulmonary syndrome. Oculomotor apraxia, squint, and bulbar symptoms were reported in 48.6%, 30.6%, and 29.4% of patients, respectively. Imiglucerase (Cerezyme) was administered to all patients for reversal of hemato-visceral and growth parameters. The overall survival rate was 71% at 20 years; 20 patients died of pulmonary and neurological diseases.ConclusionThis is the largest single-center study of GD3 patients with predominant homozygous p.Leu483Pro genotype. The patients had a very early onset of disease and severe disease parameters. The renunciation of hemato-visceral disease was achieved effectively by ERT with 71% OS, and one third of patients developed complications.