Motor Development as a Potential Marker to Monitor Infantile Pompe Disease on Enzyme Replacement Therapy

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 (Glc 4 )-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 Glc 4 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 Glc 4 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.

Clinical and Technological Dependence Characteristics on a Series of Brazilian Cases with Infantile Onset Pompe Disease in Enzyme Replacement Therapy

“…Only two cases of IOPD treated with ERT have been published in Brazil [14] [15]. A retrospective series of IOPD cases was presented in 2009 [16] with the objective of describing genotypes in IOPD and late onset Pompe Brazilian patients, however, not addressing the effects of treatment or clinical details.…”

“…Recently, MRI has been used as a non-invasive method to evaluate the muscle status in IOPD prior ERT and as a treatment follow-up [36] [37]. However, no specific instrument quantifies the degree of muscular hypotonia that could serve as a noninvasive measure to assess initial muscle damage especially in infants.Overall, most published studies, including Brazilian patients, indicates satisfactory motor development after the ERT onset in 40% of children with IOPD, up to the first three years of life[15] [25][26] [27]…”