Clinical Outcomes and Genetic Mutations in Turkish Patients with Type 1 Gaucher Disease: Insights from a...

Background: Gaucher disease (GD) is a rare autosomal recessive lysosomal storage disorder caused by mutations in the GBA1 gene, leading to deficient β-glucocerebrosidase activity. This results in the accumulation of glucocerebroside in macrophages, primarily affecting the liver, spleen, bone marrow, and bones. Understanding the clinical outcomes and genetic mutation profiles in specific populations, such as Turkish patients, is essential for optimized disease management and personalized therapy and preventing morbidity and mortality. Method: This retrospective study analyzed data from 29 Turkish patients with previously diagnosed type 1 GD at a single center between September and December 2023. Genetic analyses were performed to identify GBA1 mutations using next-generation sequencing. Genetic mutations were the primary criterion for diagnosing GD. Clinical features, treatment responses, and outcomes were evaluated. Clinical parameters included hematological findings, organomegaly, and bone involvement. Data were analyzed to identify potential correlations between genetic mutations and clinical manifestations. Results: This study included 14 male and 15 female patients, with a mean diagnosis age of 22.1 years. A significant family history was observed in 93% of cases, and 52% had consanguineous parents. Epistaxis (72%) was the most common pre-diagnosis symptom. Most patients received enzyme replacement therapy with 60 units/kg. Treatment led to significant improvements, including increased hemoglobin (21.1%), higher platelet count (86.1%), and reduced organomegaly (liver (10.02%), spleen (25.22%)). Genetic analysis identified seven mutations, with c.1226A>G (p.N409S) being the most frequent. Conclusions: This study highlights the spectrum of clinical outcomes and genetic mutations in Turkish patients with GD, emphasizing the variability in disease severity based on genotype. GD should be considered for patients with unexplained nosebleeds, hepatosplenomegaly, bone pain, weakness, or siblings or other family members with similar symptoms. The genetic analysis revealed considerable heterogeneity among patients, which indicates the necessity of observing this in the development of personalized treatment strategies. Future studies with larger cohorts and long-term follow-up are needed to further elucidate genotype-phenotype correlations in this population.