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      Next generation deep sequencing corrects diagnostic pitfalls of traditional molecular approach in a patient with prenatal onset of Pompe disease

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          Most cited references 15

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          Early treatment with alglucosidase alpha prolongs long-term survival of infants with Pompe disease.

          In a previous 52-wk trial, treatment with alglucosidase alpha markedly improved cardiomyopathy, ventilatory function, and overall survival among 18 children <7 mo old with infantile-onset Pompe disease. Sixteen of the 18 patients enrolled in an extension study, where they continued to receive alglucosidase alpha at either 20 mg/kg biweekly (n = 8) or 40 mg/kg biweekly (n = 8), for up to a total of 3 y. These children continued to exhibit the benefits of alglucosidase alpha at the age of 36 mo. Cox regression analyses showed that over the entire study period, alglucosidase alpha treatment reduced the risk of death by 95%, reduced the risk of invasive ventilation or death by 91%, and reduced the risk of any type of ventilation or death by 87%, compared with an untreated historical control group. Cardiomyopathy continued to improve and 11 patients learned and sustained substantial motor skills. No significant differences in either safety or efficacy parameters were observed between the 20 and 40 mg/kg biweekly doses. Overall, long-term alglucosidase alpha treatment markedly extended survival as well as ventilation-free survival and improved cardiomyopathy.
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            A retrospective, multinational, multicenter study on the natural history of infantile-onset Pompe disease.

            To characterize the natural progression of infantile-onset Pompe disease. Retrospective chart reviews of 168 patients with documented acid alpha-glucosidase deficiency and symptom onset by 12 months of age; Kaplan-Meier analysis of total and ventilator-free survival time; Cox proportional hazards regression modeling of mortality risk factors. The median age at symptom onset was 2.0 months (range 0 to 12 months), 4.7 months at diagnosis (range: prenatal to 4.2 months), 5.9 months at first ventilator support (range 0.1 to 31.1 months), and 8.7 months at death (range 0.3 to 73.4 months). Survival rates at 12 months of age were 25.7% overall and 16.9% ventilator-free; at 18 months 12.3% and 6.7%. Cardiomegaly (92%), hypotonia (88%), cardiomyopathy (88%), respiratory distress (78%), muscle weakness (63%), feeding difficulties (57%), and failure to thrive (53%) appeared after a median age of approximately 4.0 months. Multiple covariate analysis confirmed that early symptom onset increased risk of early death. Despite frequent therapeutic interventions, infantile-onset Pompe disease remains lethal.
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              Pompe disease in infants: improving the prognosis by newborn screening and early treatment.

              Pompe disease causes progressive, debilitating, and often life-threatening musculoskeletal, respiratory, and cardiac symptoms. Favorable outcomes with early intravenous enzyme-replacement therapy and alglucosidase alfa have been reported, but early clinical diagnosis before the development of severe symptoms has rarely been possible in infants. We recently conducted a newborn screening pilot program in Taiwan to improve the early detection of Pompe disease. Six of 206088 newborns screened tested positive and were treated for Pompe disease. Five had the rapidly progressive form of Pompe disease, characterized by cardiac and motor involvement, and were treated soon after diagnosis. The sixth patient was started on treatment at 14 months of age because of progressive muscle weakness. Outcomes were compared with treated patients whose disease was diagnosed clinically and with untreated historical control subjects. At the time of this report, patients had been treated for 14 to 32 months. The 5 infants who had early cardiac involvement demonstrated normalization of cardiac size and muscle pathology with normal physical growth and age-appropriate gains in motor development. The infant without cardiac involvement also achieved normal motor development with treatment. Survival in patients who had newborn screening was significantly improved compared with those in the untreated reference cohort (P = .001). Survival in the treated clinical comparators was reduced but not statistically different from that in the newborn screening group (P = .48). Results from this study indicate that early treatment can benefit infants with Pompe disease and highlight the advantages of early diagnosis, which can be achieved by newborn screening.
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                Author and article information

                Contributors
                (View ORCID Profile)
                Journal
                American Journal of Medical Genetics Part A
                Am J Med Genet
                Wiley
                15524825
                September 2017
                September 2017
                June 28 2017
                : 173
                : 9
                : 2500-2504
                Affiliations
                [1 ]Department of Molecular and Medical Genetics; Oregon Health and Sciences University-OHSU; Portland Oregon
                [2 ]Section of Clinical Genetics and Metabolism, Department of Pediatrics, Children's Hospital Colorado; University of Colorado Denver; Aurora Colorado
                [3 ]Department of Pediatrics; The Brooklyn Hospital Center; Brooklyn New York
                [4 ]Ambry Genetics; Aliso Viejo California
                [5 ]Department of Molecular and Human Genetics; Baylor College of Medicine; Houston Texas
                Article
                10.1002/ajmg.a.38333
                © 2017

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