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



At 2.5months, 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 11months. However, 1month 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.



This 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.
Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.
Stephanie L
SL
Austin
Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.
Andrew
A
Chiou
Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.
Baodong
B
Sun
Doctor of Physical Therapy Division, Duke University Medical Center, Durham, NC, USA.
Laura E
LE
Case
Pediatric Cardiology, Netcare Sunninghill Hospital, Johannesburg, South Africa.
Kenny
K
Govendrageloo
Pediatric Neurology, Netcare Waterfall City Hospital, Johannesburg, South Africa.
Perrin
P
Hansen
Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA. Electronic address: priya.kishnani@dm.duke.edu.
Priya S
PS
Kishnani
D055372:AMP-Activated Protein Kinases / Q000235:genetics*; D002675:Child, Preschool; D056947:Enzyme Replacement Therapy; D006008:Glycogen Storage Disease / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D008297:Male; D009154:Mutation; D016896:Treatment Outcome; D000520:alpha-Glucosidases / Q000627:therapeutic use*
C526223:PRKAG2 protein, human; D055372:AMP-Activated Protein Kinases; C509951:GAA protein, human; D000520:alpha-Glucosidases
AMP-activated protein kinase; Acid alpha-glucosidase; Cardiomyopathy; Glycogen storage disease; PRKAG2