Abstract
Pompe disease (PD) is a metabolic myopathy caused by a deficiency of acid-alpha glucosidase (GAA), a lysosomal enzyme that cleaves glycogen. The classic infantile-onset form is characterised by severe hypotonia and cardiomyopathy. Untreated patients usually die within the first year of life due to cardiorespiratory failure. Several studies involving patients with infantile-onset PD have shown that enzyme replacement therapy (ERT) with alglucosidase alfa, recombinant human GAA (rhGAA), significantly prolongs survival, decreases cardiomegaly, and improves cardiac function and conduction abnormalities. However, the efficacy on motor, cognitive and social milestones appears to be more related to the condition of the patient before the start of treatment. To date, the sample of early diagnosed and treated patients is small and the length of follow-up is still limited. We report the results of a long-term follow-up of one patient presenting severe bradycardia and cardiomyopathy at birth, diagnosed in the third day of life and successfully treated by ERT. Serum muscle enzymes at diagnosis were AST 200 U/L, ALT 99 U/L and CPK 731 U/L (n.v. 0-295); the molecular study identified the homozygous missense mutation c.1933 G> A p.Asp645Asn (GAA exon 14). Left Ventricular Mass Index (LVMI) at baseline was 171 g/m2 (Z-score = 4.3) and decreased to normal values since the 3-month follow-up. A muscle biopsy performed at 18 months after the start of therapy, showed only a low degree of muscle involvement. To our knowledge, this is the longest ERT treatment follow-up in a symptomatic neonatal patient with Pompe disease.
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Abbreviations
- CRIM:
-
Cross-reactive immunological material
- DBS:
-
Dried blood spot
- ERT:
-
Enzyme replacement therapy
- ECG:
-
Electrocardiogram
- EMG:
-
Electromyography
- GAA:
-
Acid-alpha glucosidase
- LVMI:
-
Left ventricular mass index
- MS/MS:
-
Tandem mass spectrometry
- PAS:
-
Periodic acid-Schiff
- PCR:
-
Polymerase chain reaction
- PD:
-
Pompe disease
- rhGAA:
-
Alglucosidase alfa
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Acknowledgments
The authors would like to thank Dr Chiara Marrone who helped in performing cardiac evaluations, and Mrs Stacy Skangos and Miss Sarah Lane for helping in the manuscript preparation.
Funding
This work was supported by Centro Regionale Malattie Metaboliche Ereditarie, Regione Veneto, Italy, and by Associazione Studio Malattie Metaboliche Ereditarie (A.S.M.M.E). The content of the article has not been influenced by the sponsors.
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Communicated by: Olaf Bodamer
Competing interests: None declared.
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Del Rizzo, M., Fanin, M., Cerutti, A. et al. Long-term follow-up results in enzyme replacement therapy for Pompe disease: a case report. J Inherit Metab Dis 33 (Suppl 3), 389–393 (2010). https://doi.org/10.1007/s10545-010-9195-2
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DOI: https://doi.org/10.1007/s10545-010-9195-2