van den Hout Hannerieke M P, Hop Wim, van Diggelen Otto P, Smeitink Jan A M, Smit G Peter A, Poll-The Bwee-Tien T, Bakker Henk D, Loonen M Christa B, de Klerk Johannis B C, Reuser Arnold J J, van der Ploeg Ans T
Divison of Metabolic Diseases and Genetics, Department of Pediatrics, Erasmus Medical Center/Sophia Children's Hospital, Rotterdam, The Netherlands.
Pediatrics. 2003 Aug;112(2):332-40. doi: 10.1542/peds.112.2.332.
Infantile Pompe's disease is a lethal cardiac and muscular disorder. Current developments toward enzyme replacement therapy are promising. The aim of our study is to delineate the natural course of the disease to verify endpoints of clinical studies.
A total of 20 infantile patients diagnosed by the collaborative Dutch centers and 133 cases reported in literature were included in the study. Information on clinical history, physical examination, and diagnostic parameters was collected.
The course of Pompe's disease is essentially the same in the Dutch and the general patient population. Symptoms start at a median age of 1.6 months in both groups. The median age of death is 7.7 and 6 months, respectively. Five percent of the Dutch patients and 8% of all reported patients survive beyond 1 year of age. Only 2 patients from literature became older than 18 months. A progressive cardiac hypertrophy is characteristic for infantile Pompe's disease. The diastolic thickness of the left ventricular posterior wall and cardiac weight at autopsy increase significantly with age. Motor development is severely delayed and major developmental milestones are generally not achieved. For the Dutch patient group, growth deviates significantly from normal despite start of nasogastric tube feeding. Levels of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, creatine kinase, or creatine kinase-myocardial band isoenzyme are typically elevated, although aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase increase significantly with age. The patients have fully deleterious mutations. Acid alpha-glucosidase activity is severely deficient.
Survival, decrease of the diastolic thickness of the left ventricular posterior wall, and achievement of major motor milestones are valid endpoints for therapeutic studies of infantile Pompe's disease. Mutation analysis and measurement of the alpha-glucosidase activity should be part of the enrollment program.
婴儿型庞贝病是一种致命的心脏和肌肉疾病。目前酶替代疗法的进展很有前景。我们研究的目的是描绘该疾病的自然病程，以验证临床研究的终点。
本研究纳入了荷兰合作中心诊断的20例婴儿型患者以及文献报道的133例病例。收集了临床病史、体格检查和诊断参数等信息。
荷兰患者群体和一般患者群体中庞贝病的病程基本相同。两组症状开始出现的中位年龄均为1.6个月。中位死亡年龄分别为7.7个月和6个月。5%的荷兰患者和8%的所有报道患者存活超过1岁。文献中只有2例患者年龄超过18个月。进行性心脏肥大是婴儿型庞贝病的特征。尸检时左心室后壁的舒张期厚度和心脏重量随年龄显著增加。运动发育严重延迟，通常无法达到主要发育里程碑。对于荷兰患者组，尽管开始鼻饲喂养，但生长仍明显偏离正常。天冬氨酸转氨酶、丙氨酸转氨酶、乳酸脱氢酶、肌酸激酶或肌酸激酶心肌带同工酶水平通常升高，尽管天冬氨酸转氨酶、丙氨酸转氨酶和乳酸脱氢酶随年龄显著增加。患者具有完全有害的突变。酸性α-葡萄糖苷酶活性严重缺乏。
存活、左心室后壁舒张期厚度的降低以及主要运动里程碑的实现是婴儿型庞贝病治疗研究的有效终点。突变分析和α-葡萄糖苷酶活性测量应作为入组计划的一部分。
