The most severe form of Pompe disease is typically diagnosed in infants between 3 and 5 months of age during the assessment of a respiratory infection, cardiomegaly, or hypotonia
. However, symptoms and signs of the disease might be neglected or underestimated, this resulting in delayed referral to specialized centers for diagnostic confirmation. In the described case, the hospital admission was required because of suspected liver disease, and the clinical picture of generalized hypotonia was not reported as the main clinical problem of the baby.
Severe hypotonia of the skeletal muscles associated with breathing (diaphragm, intercostal and accessory muscles) is described in Pompe disease, this resulting in inability to generate normal levels of pressure and flow in the airways during inspiration and expiration
[7–9]. These events significantly impair the removal of secretions from the airways, predisposing to even severe recurrent respiratory infections that affect morbidity and mortality of patients
. Additional mechanisms, such as the aspiration of infected secretions and/or of food in the airways, can eventually result in the development of lung lesions including segmental to lobar atelectasis and bronchiectasis. A recent study of 13 children with Pompe disease highlighted the central role of videofluoroscopy in detecting swallowing disturbances that were evident in most of the study population
. In our patient, the association of massive cardiomegaly with respiratory muscle weakness likely explains the development of progressive lung damage and irreversible respiratory failure.
During the past two decades, impressive progress has been made in the treatment of Pompe disease
. Indeed, despite enzyme replacement therapy is currently the only clinically approved treatment, different therapeutic approaches are under investigation, including enzyme enhancement therapy by pharmacological chaperones and gene therapy
[1, 11, 12]. Furthermore, substrate reduction therapy has been proved to significantly improve structural, metabolic and functional defects in a murine model of glycogenosis type II, offering a new perspective for the future treatment of this condition
Rarity of the disease and variations in clinical presentation often result in considerable delay in the diagnosis of Pompe disease, and a severely impaired health status already at time of diagnosis has been reported
. These observations, associated with the better clinical outcomes achieved when enzyme replacement therapy is started early, highlight the importance of timely detection of Pompe disease
. Particularly, since methods for dried bloodspot screening are currently being explored, neonatal screening represents the most promising option to enable earlier diagnosis, and a recent study has shown that nationwide testing of GAA-activity in dried bloodspots substantially reduced the diagnostic delay for infants with classic infantile Pompe disease
. Nevertheless, the impossibility of currently available screening techniques to discriminate between classic infantile Pompe disease and less progressive variants of the condition raises a number of ethical, legal and social considerations that warrant further research to explore the potential of neonatal screening of this disease.
In patients with Pompe disease not treated progressive respiratory failure is an important cause of morbidity and mortality
. The age at death depends on the speed of progression of the symptoms and the extent of muscle involvement
. In natural history studies of infants, the gap between diagnosis and ventilator use or death was 1 to 2 months, and nearly all cases died by the age of 18 months
Unfortunately, enzyme replacement therapy has been available in Italy only from 2006, and at the time the patient was assisted at our Department (2002) we could not prescribe it. Despite not all patients benefit equally from this therapeutic approach and, particularly, cross-reactive immunologic material-negative subjects have showed poor clinical response
, favorable outcomes with early intravenous enzyme replacement therapy have been reported
[16, 18–21]. In particular, treated patients have lower risk of undergoing mechanical ventilation, with a 100% survival rate at 18-month
. Finally, the benefits of long term therapy appear evident even at the age of 36 months