Discussion

The presentation of Pompe disease may vary from the classic infantile form to a late onset juvenile and adult form, with no cardiac manifestations.^{Reference Chen, Zhang and Quan1} The classic infantile form usually presented during the first few months of life and is characterised by hypertrophic cardiomyopathy.^{Reference Chen, Zhang and Quan1,Reference Kishnani, Hwu, Mandel, Nicolino, Yong and Corzo2} The infantile form is the most severe form and can be fatal within the first year of life if not treated early.^{Reference Bali, Goldstein and Banugaria3}

Enzyme replacement therapy is the only treatment effective in managing patients with the infantile form of Pompe disease.^{Reference Chen, Zhang and Quan1} The Food and Drug Administration approved it in 2006.^{Reference Chen, Zhang and Quan1,Reference Kishnani, Hwu, Mandel, Nicolino, Yong and Corzo2} Prior to this, supportive and conservative measures were the only treatment available. Early initiation of enzyme therapy is essential in delaying disease progression and improving outcomes. Biweekly infusions have demonstrated prolonged and invasive-ventilation-free survival.^{Reference Nicolino, Byrne and Wraith4} The greater number of receptors on cardiac muscle cell surface makes the cardiac muscles more responsive to enzyme therapy compared to skeletal muscle.^{Reference Levine, Kishnani, Chen, Herlong and Li5,Reference Raben, Jatkar and Lee6}

The clinical response to enzyme replacement therapy (ERT) depends on several factors including age of initiation, extent of pre-existing damage to the muscle as well as cross-reactive immunological material status.^{Reference Bali, Goldstein and Banugaria3} Individuals with negative status are unable to create any deficient protein and hence recognise the enzyme as a “foreign protein”. Therefore, these individuals respond poorly to the therapy due to the presence of high titers of neutralising anti-bodies to the recombinant enzyme.^{Reference Bali, Goldstein and Banugaria3} In contrast, individuals with positive status typically have some residual non-functional protein resulting in low antibody titers and therefore have a better clinical response. Determining the status is therefore crucial in order to gauge clinical response and dictates whether the patient requires immunomodulatory therapy prior to ERT.^{Reference Bali, Goldstein and Banugaria3} Both our patients were of positive status and thus expected to respond to the enzyme therapy. There are reports of a higher dose of weekly infusions resulting in better outcomes in patients with positive status.^{Reference van Gelder, Poelman and Plug7} While enzyme therapy continues to be the mainstay of treatment, studies to explore gene therapy as a definitive treatment for Pompe disease are ongoing.^{Reference Hordeaux, Dubreil and Robveille8}

Beneficial effects of enzyme therapy are unpredictable when started after the age of 5 months.^{Reference Chen, Chen and Chiu9} Cases with severe hypertrophy have been reported to be non-responsive to therapy.^{Reference Raben, Jatkar and Lee6} Thus, we believe that the delay in the diagnosis and treatment with ERT in our first case contributed to poor outcome. She developed a viral respiratory illness with complete left lung atelectasis, due to left bronchus compression secondary to cardiomegaly, resulting in decompensation, intubation and chronic ventilator dependence. Despite the initiation of weekly therapy, her cardiac status did not improve. In contrast, our second patient had a prompt diagnosis at birth with initiation of enzyme therapy at 11 days of life and a significant improvement in her cardiac status. These contrasting cases demonstrate that early diagnosis and early initiation of enzyme replacement therapy are imperative for improvement in cardiac status and increasing the likelihood of a good outcome.

Although Pompe disease is rare with an incidence of 1 in 138,000 children,^{Reference Chen, Zhang and Quan1} it should be considered as an important differential diagnosis in newborn infants with significant biventricular hypertrophy. Since the early initiation of therapy can significantly decrease the morbidity and mortality, every attempt should be made to make an early diagnosis.