Mattosova S, Hlavata A, Spalek P, Kotysova L, Macekova D, Chandoga J
Bratisl Lek Listy. 2015;116(8):502-5. doi: 10.4149/bll_2015_097.
Pompe disease is an autosomal recessive disorder of glycogen metabolism caused by deficiency in lysosomal enzyme α-glucosidase.
We present first two patients from Slovakia with confirmed Pompe disease.
Activity of α-glucosidase was measured using 4-methylumbelliferyl-α-D-glucopyranoside with the presence of acarbose, inhibitor that eliminates isoenzyme interference of maltase-glucoamylase. This methodical approach is substantial for determination of lysosomal enzyme deficiency. Using molecular genetic methods, PCR-RFLP and direct sequencing of coding region α-glucosidase gene (GAA) we have identified causal mutations in our patients.
Late-onset type of disease was confirmed by measuring α-glucosidase activity in leukocytes isolated from blood. The presence of common Caucasian mutation c.-32-13T>G was proved by genetic testing in the first patient in homozygous state. Second patient was a compound heterozygote, with mutation c.-32-13T>G on one allele and mutation A486P on the second allele.
We present a diagnostic algorithm for diagnosing the Pompe disease in patients of European origin. Enzyme replacement therapy has been used as a treatment option for improving the quality of life of patients. Early diagnosis and treatment of Pompe disease are considered to be critical for maximum efficacy of enzyme replacement therapy (Tab. 1, Fig. 3, Ref. 20).
庞贝病是一种常染色体隐性遗传性糖原代谢紊乱疾病,由溶酶体酶α-葡萄糖苷酶缺乏引起。
我们报告斯洛伐克首例确诊的两名庞贝病患者。
使用4-甲基伞形酮基-α-D-吡喃葡萄糖苷并在阿卡波糖(一种消除麦芽糖酶-葡糖淀粉酶同工酶干扰的抑制剂)存在的情况下测量α-葡萄糖苷酶活性。这种方法对于确定溶酶体酶缺乏至关重要。我们使用分子遗传学方法,即聚合酶链反应-限制性片段长度多态性(PCR-RFLP)和α-葡萄糖苷酶基因(GAA)编码区的直接测序,在我们的患者中鉴定出致病突变。
通过测量从血液中分离的白细胞中的α-葡萄糖苷酶活性,确诊为晚发型疾病。在首例患者中通过基因检测证实纯合状态下存在常见的高加索人突变c.-32-13T>G。第二例患者为复合杂合子,一个等位基因上有突变c.-32-13T>G,另一个等位基因上有突变A486P。
我们提出了一种针对欧洲裔患者诊断庞贝病的诊断算法。酶替代疗法已被用作改善患者生活质量的治疗选择。庞贝病的早期诊断和治疗被认为对于酶替代疗法的最大疗效至关重要(表1,图3,参考文献20)。