Infantile Pompe's disease under enzyme replacement therapy: Marked cognitive and speech delay but practically normal motor development

Purpose: To report a 2.5 year old girl with infantile Pompe's disease on enzyme replacement therapy started at a very early age.

Methods: Case report.

Results: First child of consanguineous parents of Turkish origin, born at term after an uneventful pregnancy. At the age of 6 weeks infantile type Pompe's disease was suspected based on hypertrophic cardiomyopathy (left ventricular mass (LMV)104g/m2) with normal ventricular function and very mild facial, axial and proximal weakness. The diagnosis was confirmed by undetectable enzyme activity of acid alpha-glucosidase activity in serum and the presence of a homozygous mutation (c1157insA) in the α-1–4-glucosidase gene. Enzyme replacement therapy was started at 8 weeks of age with 20mg/kg Myozyme® biweekly. LMV showed a significant reduction of >50% within 12 months. Motor function improved, motor milestones were in normal limits; and there was only a mild facial and axial weakness, and no respiratory involvement on polysomnography. A mild sensorineural hearing impairment was diagnosed, but was not considered relevant for speech development. Her cognitive development was slow. At age 18 months cranial MRI revealed a signal alteration of the deep white matter with sparing of U fibres. During follow up cognitive and speech development was markedly delayed, she showed behaviour problems and a significantly reduced attention span while motor development and muscle power was almost normal.

Conclusion: While cardiac hypertrophy and skeletal muscle responded well to enzyme replacement therapy, central involvement with a delay in cognitive and speech development, behavioural problems and white matter changes in MRI were prominent during follow up. Regular developmental tests including audiometric assessments are important to detect otoneurologic involvement of infantile Pompe disease that benefit from early treatment. More data on central nervous system symptoms of patients started with enzyme replacement therapy very early are needed to get a better understanding of the long term prognosis of these children.