Rossi Claudia, Ferrante Rossella, Valentinuzzi Silvia, Zucchelli Mirco, Buccolini Carlotta, Di Rado Sara, Trotta Daniela, Stuppia Liborio, Federici Luca, Aricò Maurizio
Center for Advanced Studies and Technology (CAST), "G. d'Annunzio" University of Chieti-Pescara, 66100 Chieti, Italy.
Department of Innovative Technologies in Medicine and Dentistry, "G. d'Annunzio" University of Chieti-Pescara, 66100 Chieti, Italy.
Biomedicines. 2023 Sep 29;11(10):2672. doi: 10.3390/biomedicines11102672.
Gaucher disease (GD) is an autosomal recessive inborn error of metabolism, belonging to the group of lysosomal storage diseases (LSDs). GD is caused by a defect in lysosomal glucocerebrosidase, responsible for glucosylceramide breakdown into glucose and ceramide. Because of this dysfunction, glucosylceramide progressively accumulates in the liver, spleen, bone marrow, bones, and in other tissues and organs, also causing anemia, hepatosplenomegaly, thrombocytopenia, and bone symptoms. Depending on neurological symptoms, GD is classified into three main types. Treatment options for LSDs, including enzyme replacement therapy, hematopoietic stem cell transplantation, small molecular weight pharmacologic chaperones, and, for some LSDs, gene therapy, are increasingly available. For this reason, many efforts are aimed at implementing newborn screening for LSDs since early detection accompanied by a prompt intervention has been demonstrated to be essential for reducing morbidity and mortality and for improved clinical outcomes. Herein, we report two siblings of preschool age, presenting with hepatosplenomegaly and thrombocytopenia. The initial suspicion of GD based on the clinical picture was further supported by biochemical confirmation, through newborn screening workflow, including first- and second-level testing on the same dried blood spot samples, and finally by molecular testing.
戈谢病(GD)是一种常染色体隐性遗传的先天性代谢紊乱疾病,属于溶酶体贮积病(LSD)。GD是由溶酶体葡萄糖脑苷脂酶缺陷引起的,该酶负责将葡萄糖神经酰胺分解为葡萄糖和神经酰胺。由于这种功能障碍,葡萄糖神经酰胺在肝脏、脾脏、骨髓、骨骼以及其他组织和器官中逐渐蓄积,还会导致贫血、肝脾肿大、血小板减少和骨骼症状。根据神经症状,GD主要分为三种类型。针对溶酶体贮积病的治疗方法越来越多,包括酶替代疗法、造血干细胞移植、小分子药理伴侣,对于某些溶酶体贮积病还有基因治疗。因此,许多努力都致力于开展溶酶体贮积病的新生儿筛查,因为早期检测并及时干预已被证明对于降低发病率和死亡率以及改善临床结局至关重要。在此,我们报告了两名学龄前儿童,他们表现出肝脾肿大和血小板减少。基于临床表现最初对GD的怀疑,通过新生儿筛查流程得到了生化确认的进一步支持,该流程包括对同一干血斑样本进行一级和二级检测,最终通过分子检测得以确诊。