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

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.

Genetic variant reanalysis reveals a case of Sandhoff disease with onset of infantile epileptic spasm syndrome

Background Sandhoff disease(SD)i s an autosomal recessive lysosomal disease with clinical manifestations such as epilepsy,psychomotor retardation and developmental delay.However,infantile SD with onset of infantile epilepsy spasm syndrome(IESS)is extremely rare.Case presentation The case presented here was a 22-month-old boy,who presented with IESS and psychomotor retardation/regression at 6 months of age.The patient showed progressive aggravation of seizures and excessive startle responses.The whole exome sequencing data,which initially revealed negative results,were reanalyzed and indicated a homozygous mutation at the c.1613+4del splice site of the HEXB gene.The activities ofβ-hexosaminidase A and total hexosaminidase were significantly decreased.The fundus examination showed cherry red spots at the macula.Conclusions IESS can be an epileptic phenotype of infantile SD.Clinical phenotypes should be adequately collected in genetic testing.In the case of negative sequencing results,gene variant reanalysis can be performed when the patients show clinically suspicious indications.