Clinical-genetic characteristics and treatment outcomes of Turkish children with Gaucher disease type 1 and type 3: A sixteen year single-center experience

Eur J Med Genet. 2021 Nov;64(11):104339. doi: 10.1016/j.ejmg.2021.104339.

PMID: 34500086

Ersin Gumus, Asuman Nur Karhan, Hayriye Hizarcioglu-Gulsen

Highlights: This single center experience is the first comprehensive study from Turkey not only reporting clinical and genetic characteristics of patients with Gaucher disease (GD) but also providing information on the outcomes of enzyme replacement therapy (ERT) in two different sub-types of GD.

Abstract

Objective: The patient features of Turkish children with Gaucher disease (GD) and the impact of enzyme replacement therapy (ERT) in a pediatric cohort comprising of two separate sub-types of the condition, Gaucher disease type 1 (GD1) and type 3 (GD3), were determined using data from 38 children (GD3). Both types were evenly represented (GD1/GD3 = 20/18).

Results: The most common mutant allele was L444P (35.5%), and the most common genotype was L444P/L444P (34.2%). In Turkish children with GD1 and GD3, compound heterozygosity of N370S and homozygosity of L444P were the prevailing genotypes, respectively. At the latest follow-up, none of the patients had moderate to severe thrombocytopenia, and the percentage of patients with anemia had dropped from 60% to 5.7 percent (p 0.001). In the first year of ERT, there were significant improvements in mean liver (from 2.2 to 1.6 MN, p < 0.001) and spleen (from 15.5 to 7.6 MN, p < 0.001) volumes. The percent of patients with short stature decreased from 34.3 percent to 13.3 percent (p < 0.01) at year 5, indicating that linear growth was improved. Skeletal findings included Erlenmeyer flask deformity, osteopenia, and scoliosis. Despite the fact that none of the patients had lung disease at the time of diagnosis, 20% of them had radiological abnormalities that indicated pulmonary involvement. This is the first comprehensive study from Turkey to present not only clinical and genetic characteristics of GD patients, but also information on the outcomes of ERT in two separate sub-types of GD. Turkish children with GD have a comparable genetic origin to western populations.

Conclusion: Although both subtypes of GD achieve visceral and hematological therapy targets as early as one year of ERT, achieving normal growth takes many years longer than predicted in a significant number of children with GD.

Keywords: Anemia, Enzyme replacement therapy, Hepatosplenomegaly, Lysosomal storage disease, Thrombocytopenia