Pompe disease: novel mutations and treatment outcome through newborn screening

博士 === 國立臺灣大學 === 臨床醫學研究所 === 97 === Background: Pompe disease is due to a deficiency of lysosomal acid alpha glucosidase (GAA), and currently an enzyme replacement therapy has been developed. In infantile-onset Pompe disease, enzyme replacement therapy can prolong survival and reverse cardiomegaly,...

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Main Authors: Yin-Hsiu Chien, 簡穎秀
Other Authors: Wuh-Liang Hwu
Format: Others
Language:zh-TW
Published: 2009
Online Access:http://ndltd.ncl.edu.tw/handle/06212714314510906060
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spelling ndltd-TW-097NTU055210132016-05-04T04:31:31Z http://ndltd.ncl.edu.tw/handle/06212714314510906060 Pompe disease: novel mutations and treatment outcome through newborn screening 龐貝氏症:新生兒篩檢發現個案之突變分析及治療成果 Yin-Hsiu Chien 簡穎秀 博士 國立臺灣大學 臨床醫學研究所 97 Background: Pompe disease is due to a deficiency of lysosomal acid alpha glucosidase (GAA), and currently an enzyme replacement therapy has been developed. In infantile-onset Pompe disease, enzyme replacement therapy can prolong survival and reverse cardiomegaly, however, some patients cannot regain motor or respiratory function. In late-onset Pompe disease, most of the symptoms cannot be reversed by treatment. In this study, we hypothesis that newborn screening for Pompe disease can offer an opportunity for early treatment of Pompe disease. Methods: We first analyzed phenotype and genotypes of Pompe disease in Taiwan, and explored factors which may affect the outcome. We then developed a method of newborn screening for Pompe disease, and started a pilot screening program. We analyzed the genotypes, aiming at predicting phenotypes and comparing outcomes between early treatment and late treatment. Results: Patients diagnosed clinical during infancy have poor responses to the treatment in view of skeletal muscle function. However, there was no irreversible changes in their brains. Patients with infantile-onset pompe disease identified by newborn screen could have an earlier onset of treatment and better outcomes in comparism to those identified by clinical symptoms. GAA gene mutations were similar between the two groups, and p.D645E is the most common one. We also identified babies with GAA deficiency but may have late-onset Pompe disease. They had GAA gene mutations previously seen in patients with late-onset Pompe disease, but the babies tended to have a higher incidence of mutations with unknown significance. Through newborn screening, we also identified prominent GAA gene variations in our population, including the “pseudodeficiency” allele and alleles which may modify the clinical manifestations of Pompe disease. Conclusion: Results from this study highlight the benefits of early diagnosis, which can be achieved only by newborn screening. of the intense gene variations in the population can confuse the diagnosis. The high incidence of late-onset Pompe disease from the screening program needs further confirmation, but our results do suggest the possibility of under diagnosis of Pompe disease in current clinical practice. Wuh-Liang Hwu 胡務亮 2009 學位論文 ; thesis 97 zh-TW
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language zh-TW
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description 博士 === 國立臺灣大學 === 臨床醫學研究所 === 97 === Background: Pompe disease is due to a deficiency of lysosomal acid alpha glucosidase (GAA), and currently an enzyme replacement therapy has been developed. In infantile-onset Pompe disease, enzyme replacement therapy can prolong survival and reverse cardiomegaly, however, some patients cannot regain motor or respiratory function. In late-onset Pompe disease, most of the symptoms cannot be reversed by treatment. In this study, we hypothesis that newborn screening for Pompe disease can offer an opportunity for early treatment of Pompe disease. Methods: We first analyzed phenotype and genotypes of Pompe disease in Taiwan, and explored factors which may affect the outcome. We then developed a method of newborn screening for Pompe disease, and started a pilot screening program. We analyzed the genotypes, aiming at predicting phenotypes and comparing outcomes between early treatment and late treatment. Results: Patients diagnosed clinical during infancy have poor responses to the treatment in view of skeletal muscle function. However, there was no irreversible changes in their brains. Patients with infantile-onset pompe disease identified by newborn screen could have an earlier onset of treatment and better outcomes in comparism to those identified by clinical symptoms. GAA gene mutations were similar between the two groups, and p.D645E is the most common one. We also identified babies with GAA deficiency but may have late-onset Pompe disease. They had GAA gene mutations previously seen in patients with late-onset Pompe disease, but the babies tended to have a higher incidence of mutations with unknown significance. Through newborn screening, we also identified prominent GAA gene variations in our population, including the “pseudodeficiency” allele and alleles which may modify the clinical manifestations of Pompe disease. Conclusion: Results from this study highlight the benefits of early diagnosis, which can be achieved only by newborn screening. of the intense gene variations in the population can confuse the diagnosis. The high incidence of late-onset Pompe disease from the screening program needs further confirmation, but our results do suggest the possibility of under diagnosis of Pompe disease in current clinical practice.
author2 Wuh-Liang Hwu
author_facet Wuh-Liang Hwu
Yin-Hsiu Chien
簡穎秀
author Yin-Hsiu Chien
簡穎秀
spellingShingle Yin-Hsiu Chien
簡穎秀
Pompe disease: novel mutations and treatment outcome through newborn screening
author_sort Yin-Hsiu Chien
title Pompe disease: novel mutations and treatment outcome through newborn screening
title_short Pompe disease: novel mutations and treatment outcome through newborn screening
title_full Pompe disease: novel mutations and treatment outcome through newborn screening
title_fullStr Pompe disease: novel mutations and treatment outcome through newborn screening
title_full_unstemmed Pompe disease: novel mutations and treatment outcome through newborn screening
title_sort pompe disease: novel mutations and treatment outcome through newborn screening
publishDate 2009
url http://ndltd.ncl.edu.tw/handle/06212714314510906060
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