[Clinical phenotype and genotype of Gaucher disease in 14 children]

Objective: To analyze the clinical and genetical characteristics of children with Gaucher disease and to explore the relationship between genotype and phenotype. Methods: In this retrospective study, the clinical data of 14 children with Gaucher disease diagnosed in Children's Hospital of Nanjing Medical University from August 2016 to October 2021 were analyzed. Their general conditions, clinical manifestations, laboratory tests and gene variations were collected, followed by the analysis of the clinical phenotypes and genotypes. Results: Among 14 children diagnosed with Gaucher disease, 9 were males and 5 were females, with the age of diagnosis ranging from 0.7 to 15.8 years. There were 10 patients with type 1 Gaucher disease, 2 patients with type 2, and 2 patients with type 3. The most common clinical manifestations were splenomegaly, thrombocytopenia (14 cases), hepatomegaly (8 cases) and anemia (8 cases). There were 6 patients with growth retardation, and 5 patients lag in height compared with their peers. Bone abnormalities were revealed by magnetic resonance imaging in 7 type 1 Gaucher disease patients, but only 1 patient experienced bone pain. Patients with type 2 and type 3 Gaucher disease also presented with convulsions, nystagmus and hearing loss. Gaucher cells were found in bone marrow smears in 12 patients. The glucocerebrosidase gene variations identified in 13 patients were heterozygous and in 1 type 1 patient was homozygous of L483P. L483P variation accounted for 33%(10/30) of the variation alleles, followed by V414L, D448H and R159W. The variation alleles were L483P and L422R, F252I and L483P in 2 children with severe neurological manifestations of Gaucher disease. A novel variation c.22A>G was detected. Conclusions: Splenomegaly and thrombocytopenia are the main clinical presentations of Gaucher disease in children and bone lesions revealed by radiologic imaging appear prior to the occurrence of bone diseases, type 2 and type 3 Gaucher disease also present growth retardation and neurological manifestation. The most frequent variant allele is L483P, which are detected in all 3 subtypes of Gaucher disease. The L422R, F252I gene variants correlated with the neuronopathic phenotype.