Abstract
After Enzyme Replacement Therapy (ERT) using recombinant human acid alpha-glucosidase (rhGAA), survival of Infantile Pompe Disease (IPD) patients through the first 18 months of age has been documented and acquisitions of motor development are an important outcome, but description of its course is scarce. Objective: To describe the motor development in an IPD patient and its correlation with clinical conditions during the first 18 months on ERT with rhGAA. Methods: By longitudinal observational study of an IPD case at early stage. Clinical and biochemical characteristics were obtained from patient records. Echocardiogram assessed cardiac indexes and the urinary biomarker—glucose tetrasaccharide (Glc4)—was obtained by HPLC/UV, following sample derivatization with butyl 4-amino benzoate and analysis on a C18 stationary phase column. Motor skills were evaluated with Alberta Infant of Motor Scale (AIMS) and motor delay was considered as motor percentile (p) below 10. Descriptive statistical analysis was carried out and t-test was used to calculate the differences among means, with significance level defined as p value < 0.05. Results: After ERT beginning amelioration of the cardiomyopathy with reduced left ventricle mass index (LVMI) from the 2nd month onwards was observed, but above the upper normal limit for healthy children and CRIM-positive IPD patients. Although GAA antibodies level remained above the recommended titers and fluctuating elevation of Glc4 quantified, motor development analysis showed an ascendant curve expected for age within achievement of independent ambulation. Motor delay after pneumonia and maintenance of hypotonia were noted. Variation of Glc4 appeared long after a transitory intercurrence. Conclusion: In an IPD case, motor development can have normal evolution despite hypotonia. Motor analysis seems to be sensitive to follow-up clinical intercurrences. To elucidate the interaction among prognostic factors and outcomes, further clinical studies need to be conducted.
Highlights
This study aimed to describe the characteristics of motor development evaluation of a child with Infantile Pompe Disease (IPD) on early Enzyme Replacement Therapy (ERT) scheme, outside clinical trials and its relationship with clinical conditions during the first 18 months of life, as a potential marker of disease
Several prognostic factors are recognized in patients with IPD, among which residual Acid α-glucosidase Glc4 (GAA) enzyme level, age at beginning of ERT treatment, Cross-reactive immunologic material (CRIM) status, extent of initial muscle damage and maintenance of high antibody titers may be of importance [19] [20] [21]
The ERT treatment with recombinant human GAA enzyme (rhGAA) in our patient resulted in an improvement of the cardiomyopathy with reduced left ventricle mass index (LVMI) from the 2nd month onwards; it remained above the upper normal limit for healthy children [18], it was similar to IPD patients studied
Summary
With the approval of Pompe disease treatment by enzyme replacement therapy (ERT) with recombinant human GAA enzyme (rhGAA) [2], there was a change in the natural history of the disease, with increased life expectancy and changes in phenotypic characteristics so far known in the infantile form [3] [4] [5]. Infantile Pompe Disease (IPD) is the rarest and most severe form of the disease, with an incidence of 1:138,000 live births and onset of symptoms in the first several months of life. Cardiac symptoms progress well with ERT treatment; recent studies suggest that muscle involvement seems not to reverse completely, regardless of the medication dose used [8] [9]
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