Ramaswami Uma, Whybra Catharina, Parini Rosella, Pintos-Morell Guillem, Mehta Atul, Sunder-Plassmann Gere, Widmer Urs, Beck Michael
Department of Paediatric Endocrinology, Diabetes and Metabolism, Addenbrooke's Hospital, Cambridge, UK.
Acta Paediatr. 2006 Jan;95(1):86-92. doi: 10.1080/08035250500275022.
Fabry disease is a rare X-linked disorder caused by deficient activity of the enzyme alpha-galactosidase A. This produces progressive lysosomal accumulation of globotriaosylceramide throughout the body, leading to organ failure and premature death.
Here, we present the clinical manifestations of Fabry disease in children enrolled in FOS--the Fabry Outcome Survey--a European database of the natural history of Fabry disease and the effects of enzyme replacement therapy with agalsidase alfa (Replagal).
Currently, there are 545 patients in FOS, from 11 European countries. We analysed the baseline demographic and clinical characteristics of 82 of these patients (40 boys, 42 girls) who were below 18 y of age. The median age at evaluation (defined as the median age at entry into FOS) was 12.5 and 13.2 y for boys and girls, respectively.
The most frequent early clinical manifestations of Fabry disease were neurological (acroparaesthesiae, altered temperature sensitivity) and gastrointestinal symptoms (altered bowel habits and abdominal pain), which were documented in about 80% and 60% of patients, respectively, at the time of evaluation and subsequent entry into FOS. Tinnitus, vertigo, fatigue and angiokeratoma were present in over 40% of patients. Symptoms were noted in early childhood and occurred with similar frequency in boys and girls, although the onset of symptoms was 2-5 y later in girls than in boys. There was an approximately 3-y delay from onset of symptoms to diagnosis, and patients were frequently misdiagnosed.
Although the life-threatening complications of Fabry disease, such as stroke and renal and heart failure, are not seen in children, the present analysis shows that other symptoms are common and may have an impact on quality of life.
法布里病是一种罕见的X连锁疾病，由α-半乳糖苷酶A活性不足引起。这会导致全身溶酶体中球三糖神经酰胺进行性蓄积，进而导致器官衰竭和过早死亡。
在此，我们展示了参与法布里病结局调查（FOS）的儿童中法布里病的临床表现。FOS是一个欧洲数据库，记录了法布里病的自然病史以及阿加糖酶α（瑞普佳）酶替代疗法的效果。
目前，FOS中有来自11个欧洲国家的545名患者。我们分析了其中82名年龄在18岁以下患者（40名男孩，42名女孩）的基线人口统计学和临床特征。评估时的中位年龄（定义为进入FOS时的中位年龄）男孩为12.5岁，女孩为13.2岁。
法布里病最常见的早期临床表现是神经系统症状（肢端感觉异常、温度敏感性改变）和胃肠道症状（排便习惯改变和腹痛），在评估时及随后进入FOS时，分别约80%和60%的患者出现这些症状。超过40%的患者有耳鸣、眩晕、疲劳和血管角质瘤。症状在幼儿期出现，男孩和女孩出现的频率相似，尽管女孩症状出现的时间比男孩晚2 - 5年。从症状出现到诊断大约有3年的延迟，患者常被误诊。
虽然法布里病危及生命的并发症，如中风、肾衰竭和心力衰竭在儿童中未见，但目前的分析表明其他症状很常见，可能会影响生活质量。
