■粘多糖贮积症IIIA型(MPSIIIA,SanfilippoA综合征)是一种由溶酶体磺酰胺酶缺乏引起的慢性进行性神经退行性贮积症。临床特征是睡眠障碍,行为异常和认知丧失,言语和运动能力。受影响的儿童从第二年开始表现出发育缓慢,痴呆症在5岁时发生,然后在生命的第二个十年死亡。只有少数关于HSCT在MPSIIIA中的研究已经发表,没有明确的治疗益处。
■本研究总结了一名患有MPSIIIA的女孩在2.5岁时接受HSCT的临床结果。将她的临床过程与六名未经治疗的MPSIIIA患者携带相同突变的自然史进行了比较(p。SGSH基因中的R74C和p。R245H)。
■成功实施HSCT八年后,患者表现出整体发育迟缓。然而,认知能力继续发展,尽管非常缓慢。没有消退的迹象。她可以用简短的句子说话,具有良好的运动能力,并独自进行基本的日常生活活动。她没有出现睡眠问题,但是行为异常是深刻的。相比之下,6例SGSH基因突变相同的未经治疗的患者表现出典型的进行性病程,早期和持续能力丧失.
■目前的数据表明,在MPSIIIA的早期阶段进行HSCT对认知技能的有益影响,运动功能和生活质量。
BACKGROUND: Mucopolysaccharidosis type IIIA (MPS IIIA, Sanfilippo A syndrome) is a chronic progressive neurodegenerative storage disorder caused by a deficiency of lysosomal sulfamidase. The clinical hallmarks are sleep disturbances, behavioral abnormalities and loss of cognitive, speech and motor abilities. Affected children show developmental slowing from the second year of life, dementia occurs by the age of 5 years followed by death in the second decade of life. Only a few studies concerning HSCT in MPS IIIA have been published and do not document a clear benefit of treatment.
METHODS: The present study summarizes the clinical outcome of a girl with MPS IIIA who received HSCT at the age of 2.5 years. Her clinical course was compared with the natural history of six untreated MPS IIIA patients carrying the same mutations (p.R74C and p. R245H) in the SGSH-gene.
RESULTS: Eight years after successful HSCT, the patient showed a global developmental delay. However, cognitive abilities continued to develop, albeit very slowly. There was no sign of regression. She could talk in short sentences, had good motor abilities and performed basic daily living activities by herself. She did not present with sleeping problems, but behavioral abnormalities were profound. In contrast, the six untreated patients with identical mutations in the SGSH-gene showed the typical progressive course of disease with early and continuous loss of abilities.
CONCLUSIONS: The present data suggest a beneficial effect of HSCT performed at an early stage of MPS IIIA on cognitive skills, motor function and quality of life.