Owens Penny, Wong Melanie, Bhattacharya Kaustuv, Ellaway Carolyn
Genetic Metabolic Disorders Service, Western Sydney Genetics Program, Children's Hospital at Westmead, Sydney, New South Wales, Australia.
Department of Immunology, Children's Hospital at Westmead, Sydney, New South Wales, Australia.
J Paediatr Child Health. 2018 Nov;54(11):1255-1261. doi: 10.1111/jpc.14070. Epub 2018 Jun 11.
Pompe disease is a rare, autosomal, recessive disorder. Alterations in the gene encoding lysosomal acid alpha-glucosidase cause impaired glycogen degradation and resultant lysosomal glycogen accumulation. Classic infantile-onset Pompe disease (IPD) manifests soon after birth, severe cases have complete/near complete enzyme deficiency. IPD is associated with a broad spectrum of non-specific clinical features, and diagnostic delays are common. Without treatment, death typically occurs within the first 2 years of life. We present case experiences to help expand paediatricians' understanding of factors contributing to diagnostic delay, clinical decline and to highlight the need for timely therapy.
Data were extracted from IPD cases managed at our hospital. Key aspects of clinical presentation, diagnosis, genetic variations, management and overall outcomes were collated then compared with what is already known in the literature.
We report four IPD cases (three female). Two patients were cross-reactive immunological material negative. Age at symptom onset was 3-9 months, presenting clinical features were varied, and confirmatory diagnosis was significantly delayed in one patient. In concert with the literature, cardiomegaly, ventricular hypertrophy and delayed developmental milestones were seen in all four cases. Our cases demonstrate a range of disease severity, response to enzyme replacement therapy and antibody development. Significant immune responses were seen in two cases (one cross-reactive immunological material positive); despite immunomodulation therapy, both were associated with fatal outcomes.
Timely diagnosis and initiation of enzyme replacement therapy is critical to patient outcomes as IPD progresses rapidly and irreversible changes in clinical status may occur during the delay.
庞贝病是一种罕见的常染色体隐性疾病。编码溶酶体酸性α-葡萄糖苷酶的基因发生改变，导致糖原降解受损，进而引起溶酶体糖原蓄积。典型的婴儿型庞贝病（IPD）在出生后不久就会出现症状，严重病例存在完全/近乎完全的酶缺乏。IPD与一系列非特异性临床特征相关，诊断延迟很常见。未经治疗，通常在生命的头2年内死亡。我们展示病例经验，以帮助儿科医生扩大对导致诊断延迟、临床病情恶化因素的理解，并强调及时治疗的必要性。
从我院管理的IPD病例中提取数据。整理临床表现、诊断、基因变异、治疗及总体结局的关键方面，然后与文献中已知内容进行比较。
我们报告4例IPD病例（3例女性）。2例患者交叉反应免疫物质阴性。症状出现时的年龄为3 - 9个月，临床表现多样，1例患者确诊明显延迟。与文献一致，所有4例均出现心脏肥大、心室肥厚及发育里程碑延迟。我们的病例显示了一系列疾病严重程度、对酶替代治疗的反应及抗体产生情况。2例（1例交叉反应免疫物质阳性）出现显著免疫反应；尽管进行了免疫调节治疗，但均与致命结局相关。
由于IPD进展迅速，在诊断延迟期间临床状况可能发生不可逆变化，因此及时诊断并开始酶替代治疗对患者预后至关重要。
