Meyer Ann, Kossow Kai, Gal Andreas, Mühlhausen Chris, Ullrich Kurt, Braulke Thomas, Muschol Nicole
University Medical Center Hamburg-Eppendorf, Metabolic Center, Department of Pediatrics, Martinistrasse 52, Building N23, 20246 Hamburg, Germany.
Pediatrics. 2007 Nov;120(5):e1255-61. doi: 10.1542/peds.2007-0282. Epub 2007 Oct 15.
Mucopolysaccharidosis types IIIA through IIID (Sanfilippo syndrome) are caused by deficiencies of enzymes involved in the degradation of heparan sulfate. The onset and severity of the disease are highly variable. The purpose of this study was to describe the natural course of mucopolysaccharidosis type IIIA in a large cohort of patients.
The natural course of mucopolysaccharidosis type IIIA was assessed in 71 patients by using a detailed questionnaire and a 4-point scoring system and compared with the course of the disease in 14 patients with mucopolysaccharidosis type IIIB and 4 patients with mucopolysaccharidosis type IIIC.
In the cohort of patients with mucopolysaccharidosis type IIIA, first symptoms of disease were observed, on average, at 7 months of age. Speech and motor development were delayed in 66.2% and 33.9% of patients, respectively. The median age at diagnosis was 4.5 years. The onset of regression in speech, motor, and cognitive function was observed at an average age of 3.3 years. The loss of all 3 of the assessed abilities was observed at an average age of 12.5 years. Speech was lost before motor and cognitive functions. In a small group of patients who were >12.5 years of age (9.9%), speech, motor, and cognitive skills were partially preserved up to a maximum age of 23.8 years.
To our knowledge, this is the first systematic and comprehensive study on the natural course of mucopolysaccharidosis type IIIA. The 4-point scoring system may be used to classify patients into groups with a rapid or slower course of the disease. This may have an important impact on parental counseling as well as therapeutic interventions.
ⅢA型至ⅢD型黏多糖贮积症（Sanfilippo综合征）是由参与硫酸乙酰肝素降解的酶缺乏引起的。该病的发病和严重程度差异很大。本研究的目的是描述一大群ⅢA型黏多糖贮积症患者的自然病程。
通过详细问卷和4分评分系统对71例ⅢA型黏多糖贮积症患者的自然病程进行评估，并与14例ⅢB型黏多糖贮积症患者和4例ⅢC型黏多糖贮积症患者的病程进行比较。
在ⅢA型黏多糖贮积症患者队列中，疾病的首发症状平均在7个月大时出现。分别有66.2%和33.9%的患者出现言语和运动发育迟缓。诊断时的中位年龄为4.5岁。言语、运动和认知功能衰退的起始平均年龄为3.3岁。所有三项评估能力丧失的平均年龄为12.5岁。言语在运动和认知功能之前丧失。在一小群年龄大于12.5岁（9.9%）的患者中，言语、运动和认知技能部分保留，最大年龄为23.8岁。
据我们所知，这是第一项关于ⅢA型黏多糖贮积症自然病程的系统全面研究。4分评分系统可用于将患者分为疾病进展快或慢的组。这可能对家长咨询以及治疗干预产生重要影响。
