P0393 - Hypertrophic Cardiomyopathy in Infantile-Onset Pompe Disease Treated with Enzyme Replacement Therapy

Alpha glucosidase deficiency, or Pompe disease, is characterized by the inappropriate accumulation of glycogen within cardiac and skeletal muscle cells. Children with Infantile-Onset Pompe disease (IOPD) have demonstrated progressive hypertrophic cardiomyopathy (HCM) that does not respond to traditional medications. In 2014, the FDA approved the use of enzyme-replacement therapy (ERT) for the treatment of HCM associated with IOPD. We present three cases treated at Riley Hospital for Children of hypertrophic cardiomyopathy due to IOPD that were responsive to ERT.

The patients ranged from ages zero to three months at the time of their diagnosis with hypertrophic cardiomyopathy and presented to Riley Hospital for Children between 2012 and 2020. All of the patients were confirmed to have CRIM-positive IOPD with molecular testing. The patients had an interventricular septum (IVS) thickness ranging from 0.8-1.63 centimeters (Z-score 5.7 to 10.43) at the time of their initial echocardiogram performed at our institution. The left ventricular posterior wall (LVPW) measured 0.87-1.63 centimeters (Z-score 6.52 to 8.37).

Patients were started on enzyme-replacement therapy between ages three and four months. Of the three patients, two began ERT at our institution. There were varying approaches to initial dosing, reflecting the best practice recommendations at the time of presentation. Currently, both children are receiving ERT every two weeks. Echocardiograms obtained at twelve months of age showed improvement of the IVS to 0.5-1.07 cm (Z-score 0.55-4.23) and LVPW to 0.35-0.67 (Z-score -2.22 to 3.18). These patients are followed by cardiology and cardiovascular genetics regularly and remain asymptomatic from a cardiac perspective. Additionally, both patients do not require supplemental oxygen during the day, with one patient requiring BiPAP at night. These patients are now 8 years and 18 months old. With maintenance ERT, they have both made marked physical and developmental advancements.

The third patient began ERT at an outside institution and transferred care to us at seven months of age. Prior to transfer, he was being treated with ERT at 20 mg/kg every other week and was unable to wean from mechanical ventilation. He was also found to have elevated antibody titers to ERT, requiring aggressive immune modulation and an increase in his infusion dose to 40 mg/kg twice weekly. He was subsequently able to wean to nasal cannula with nighttime BiPAP and was discharged home. His most recent echocardiogram, obtained at ten months of age, shows an improvement of his IVS to 0.64 cm (Z-score 4.13) and LVPW 0.53 cm (Z-score 1.64). At 11 months old now, he demonstrates significant motor and developmental delays.

Our institution’s experience shows that children with IOPD-associated hypertrophic cardiomyopathy have dramatic improvement of their cardiac outcomes in response to ERT while also allowing significant improvements in motor and developmental abilities.