Alglucosidase alfa enzyme replacement therapy as a therapeutic approach for a patient presenting with a PRKAG2 mutation

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• 作者：Stephanie L. Austin^a ; Andrew Chiou^a ; Baodong Sun^a ; Laura E. Case^b ; Kenny Govendrageloo^c ; Perrin Hansen^d ; Priya S. Kishnani^a ; ^{priya.kishnani@dm.duke.edu}
• 关键词：ERT ; enzyme replacement therapy ; GAA ; acid alpha-glucosidase ; GSD ; glycogen storage diseases ; AMPK ; AMP-activated protein kinase ; rhGAA ; recombinant human GAA ; IVS ; interventricular septum ; LVPW ; left ventricular posterior wall ; PT ; physical therapy ; AST ; aspartate aminotransferase ; ALT ; alanine transaminase ; MABC ; Movement ABC ; MDC ; minimal detectable change ; MID ; minimal important difference ; M-FUN ; Miller Function and Participation Scales ; GLUT4 ; glucose transporter 4 ; G6P ; glucose 6-phosphat
• 刊名：Molecular Genetics and Metabolism
• 出版年：2017
• 出版时间：January-February 2017
• 年：2017
• 卷：120
• 期：1-2
• 页码：96-100
• 全文大小：456 K
• 卷排序：120

文摘

PRKAG2 syndrome, an autosomal dominant disorder, is characterized by severe infantile hypertrophic cardiomyopathy and heart rhythm disturbances to cases with a later presentation and a spectrum of manifestations including cardiac manifestations, myopathy and seizures. The cardiac features of PRKAG2 resemble the cardiac manifestations of Pompe disease. We present a patient who was initially diagnosed with Pompe disease and treated with alglucosidase-alfa enzyme replacement therapy (ERT); however, he was eventually diagnosed to carrying a PRKAG2 pathogenic gene mutation; he did not have Pompe disease instead he was a carrier for the common adult leaky splice site mutation in the GAA gene.Case reportAt 2.5 months, the patient had hypotonia/generalized muscle weakness, a diagnosis of non-classic infantile Pompe disease was made based on low acid alpha-glucosidase activity and the patient started on ERT at 11 months. However, 1 month later, the patient began to have seizures. As the patient's medical history was somewhat unusual for infantile Pompe disease, further evaluation was initiated and included a glycogen storage disease sequencing panel which showed that the patient had a pathogenic mutation in PRKAG2 which had been reported previously. ERT was discontinued and patient had a progression of motor deficits. ERT was reinitiated by the treating physician, and a clinical benefit was noted.ConclusionThis report outlines the benefits of ERT with alglucosidase alfa in a patient with PRKAG2 syndrome, the decline in his condition when the ERT infusions were discontinued, and the significant positive response when ERT was reinitiated.