Infantile Pompe disease is a rare inborn error of metabolism characterised by severe hypertrophic cardiomyopathy and generalised hypotonia occurring in infancy. The prognosis is quite poor, with the median age of death being <9 months of age and the overwhelming majority dying within the first year of life.Reference Kishnani, Hwu, Mandel, Nicolino, Yong and Corzo 1
Case report
A 3-month-old girl presented to the emergency department with a 2-week history of vomiting and poor weight gain. The mother reported that the patient had previously been diagnosed with an “enlarged heart” at another institution and was started on propranolol but had no further work-up. The mother sought a second opinion because the symptoms were persisting.
Initial work-up included an electrocardiogram revealing diffuse high-voltage QRS complexes and a short PR interval of 90 ms. Echocardiogram on admission showed an obstructive hypertrophic cardiomyopathy with massive concentric left ventricular hypertrophy and moderate left ventricle mid-cavity obstruction with a peak gradient of 46 mmHg. In addition, the patient had diffuse mild hypotonia.
A metabolic work-up was initiated. Dried blood spot assay revealed reduced acid alpha glucosidase activity suggestive of Pompe disease. Subsequent gene testing confirmed the diagnosis of Pompe disease with three separate heterozygous gene mutations associated with Pompe disease. First, a single nucleotide change was found within the first intron of the GAA gene (c.-32-13 T>G). Second, a single nucleotide change (c.1841 C>A) in exon 13 was noted. Third, there was a single nucleotide change (c.1856 G>A) in exon 13. The patient was started on alpha-glucosidase enzyme replacement therapy in the form of MyozymeTM IV every 2 weeks. MyozymeTM was transitioned to LumizymeTM at 1 year of age. Propranolol was continued throughout.
At the most recent follow-up, the patient was 18 months old and had been on enzyme replacement therapy for 15 months. There was significant gradual improvement in left ventricular hypertrophy. At presentation, the left ventricle diastolic posterior wall thickness z-score was 6.7 and the interventricular septum diastolic wall thickness z-score was 6.3 (Fig 1). At the most recent follow-up, the left ventricle diastolic posterior wall thickness z-score was 2.9 and the interventricular septum diastolic wall thickness z-score was 1.2, and there was no mid-cavity or left ventricle outflow tract obstruction (Fig 2). The patient now has mild hypotonia but is otherwise asymptomatic with normal neurodevelopment.
Figure 1 Echocardiogram at presentation. Left ventricular echocardiographic images (long axis on left and short axis on right) demonstrate dramatic concentric hypertrophy. Note the markedly hypertrophied interventricular septum (white arrows) and posterior left ventricular wall (yellow arrows) during diastole.
Figure 2 Echocardiogram after 15 months of enzyme replacement therapy. Left ventricular echocardiographic images (long axis on left and short axis on right) show marked improvement in concentric hypertrophy. Note how much thinner the interventricular septum (white arrows) and posterior left ventricular wall (yellow arrows) are during diastole.
Discussion
Infantile Pompe disease is rapidly progressive, typically resulting in end-stage heart failure secondary to obstructive hypertrophic cardiomyopathy leading to death in the first year of life. This case report presents a patient with severe cardiomyopathy secondary to infantile Pompe disease who showed dramatic improvement on enzyme replacement therapy.
Recent international studies have shown promise with the use of enzyme replacement therapy in infantile Pompe disease; however, very little has been published about this topic in the United States of America.Reference Amartino and Cavagnari 2 – Reference Klinge, Straub and Neudorf 6 Although enzyme replacement therapy is not without risk,Reference Case, Hanna and Frush 7 , Reference McDowell, Li and Benjamin 8 this case demonstrates that benefit can be obtained in severe infantile Pompe disease, including resolution of severe cardiomyopathy. Continued studies that characterise the risks and benefits of such therapy in infantile Pompe disease are warranted.
Conclusions
Cardiac manifestations can markedly improve in infantile Pompe disease with the use of enzyme replacement therapy. Continued long-term monitoring of these patients is warranted to not only guide treatment, but also to better understand long-term outcomes in patients receiving enzyme replacement therapy beginning in infancy.
Acknowledgements
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Financial Support
This research received no specific grant from any funding agency, commercial or not-for-profit sectors.
Conflicts of Interest
None.
