Thirty-four novel mutations of the GLA gene in 121 patients with Fabry disease

Fabry disease (FD) is an X-chromosomal disorder caused by mutations in the GLA gene encoding the lysosomal enzyme alpha-galactosidase A. We performed mutation screening on a cohort of 121 patients including 84 male and 37 female index cases and identified a total of 90 different mutations, 34 of which are reported for the first time here. Both point mutations (74.4%) and 'short length' rearrangements (25.6%) were found, including missense (54.4%), nonsense (14.4%), and splice site point mutations (5.6%), deletions (17.8%) or insertions/duplications (5.6%) of a few nucleotides, and complex rearrangements including larger deletions (2.2%). GLA mutations were identified in 82 (97.6%) of the 84…

A novel tool for mapping disease severity and outcomes in patients with Gaucher disease utilising the therapeutic goals

P1211 : Efficacy and safety of sebelipase alfa in children and adults with lysosomal acid lipase deficiency: Results of a phase 3 trial

A Phase 3 Trial of Sebelipase Alfa in Lysosomal Acid Lipase Deficiency

BackgroundLysosomal acid lipase is an essential lipid-metabolizing enzyme that breaks down endocytosed lipid particles and regulates lipid metabolism. We conducted a phase 3 trial of enzyme-replacement therapy in children and adults with lysosomal acid lipase deficiency, an underappreciated cause of cirrhosis and severe dyslipidemia. MethodsIn this multicenter, randomized, double-blind, placebo-controlled study involving 66 patients, we evaluated the safety and effectiveness of enzyme-replacement therapy with sebelipase alfa (administered intravenously at a dose of 1 mg per kilogram of body weight every other week); the placebo-controlled phase of the study was 20 weeks long and was followe…

Exploring the patient journey to diagnosis of Gaucher disease from the perspective of 212 patients with Gaucher disease and 16 Gaucher expert physicians

Gaucher disease (GD) is a rare hereditary disorder caused by a deficiency of the lysosomal enzyme β-glucocerebrosidase. Diagnosis is challenging owing to a wide variability in clinical manifestations and severity of symptoms. Many patients may experience marked delays in obtaining a definitive diagnosis. The two surveys reported herein aimed to explore the patient journey to diagnosis of GD from the perspectives of Gaucher expert physicians and patients. Findings from the surveys revealed that many patients experienced diagnostic delays and misdiagnoses, with nearly 1 in 6 patients stating that they were not diagnosed with GD for 7years or more after first consulting a doctor. Physicians an…