Sun X Y, Xue Y, Wang Y P, Huang J, Lin R F, Kang M Y, Fang Y J
Department of Hematological Oncology, Children's Hospital of Nanjing Medical University, Nanjing 210008, China.
Zhonghua Er Ke Za Zhi. 2022 Jun 2;60(6):527-532. doi: 10.3760/cma.j.cn112140-20220228-00159.
To analyze the clinical and genetical characteristics of children with Gaucher disease and to explore the relationship between genotype and phenotype. 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. 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. 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.
分析戈谢病患儿的临床和遗传特征，探讨基因型与表型之间的关系。在这项回顾性研究中，分析了2016年8月至2021年10月在南京医科大学附属儿童医院确诊的14例戈谢病患儿的临床资料。收集了他们的一般情况、临床表现、实验室检查和基因变异情况，随后对临床表型和基因型进行分析。在14例确诊为戈谢病的患儿中，男性9例，女性5例，诊断年龄为0.7至15.8岁。1型戈谢病患者10例，2型2例，3型2例。最常见的临床表现为脾肿大、血小板减少（14例）、肝肿大（8例）和贫血（8例）。有6例生长发育迟缓，5例身高低于同龄人。7例1型戈谢病患者通过磁共振成像显示有骨骼异常，但只有1例患者有骨痛。2型和3型戈谢病患者还出现惊厥、眼球震颤和听力丧失。12例患者骨髓涂片发现戈谢细胞。13例患者鉴定出的葡萄糖脑苷脂酶基因变异为杂合子，1例1型患者为L483P纯合子。L483P变异占变异等位基因的33%（10/30），其次是V414L、D448H和R159W。2例有严重神经系统表现的戈谢病患儿的变异等位基因为L483P和L422R、F252I和L483P。检测到一个新的变异c.22A>G。脾肿大和血小板减少是儿童戈谢病的主要临床表现，影像学显示的骨病变先于骨病出现，2型和3型戈谢病还表现出生长发育迟缓及神经系统表现。最常见的变异等位基因为L483P，在戈谢病的所有3个亚型中均有检测到。L422R、F252I基因变异与神经病变表型相关。
