Aim To examine the long‐term consequences of glycogen storage in the central nervous system (CNS) for classic infantile Pompe disease using enzyme replacement therapy. Method Using neuropsychological tests and brain magnetic resonance imaging (MRI), we prospectively assessed a cohort of 11 classic infantile Pompe patients aged up to 17 years. Results From approximately age 2 years onwards, brain MRI showed involvement of the periventricular white matter and centrum semiovale. After 8 years of age, additional white‐matter abnormalities occurred in the corpus callosum, internal and external capsule, and subcortical areas. From 11 years of age, white‐matter abnormalities were also found in the brainstem. Although there seemed to be a characteristic pattern of involvement over time, there were considerable variations between patients, reflected by variations in neuropsychological development. Cognitive development ranged from stable and normal to declines that lead to intellectual disabilities. Interpretation As treatment enables patients with classic infantile Pompe disease to reach adulthood, white‐matter abnormalities are becoming increasingly evident, affecting the neuropsychological development. Therefore, we advise follow‐up programs are expanded to capture CNS involvement in larger, international patient cohorts, to incorporate our findings in the counselling of parents before the start of treatment, and to include the brain as an additional target in the development of next‐generation therapeutic strategies for classic infantile Pompe disease. What this paper adds In our long‐term survivors treated intravenously with enzyme replacement therapy, we found slowly progressive symmetric white‐matter abnormalities. Cognitive development varied from stable and normal to declines towards intellectual disabilities.

Our data show that infants with sonographic signs of brain atrophy at discharge achieve lower scores in neurodevelopmental testing at 3 y.

Background: Intraventricular haemorrhage and periventricular leukomalacia are associated with poor outcome of very preterm infants, while the role of more subtle cerebral alterations, as detected by cranial ultrasound, is less clear. Aim: In this study, we related periventricular echodensities and signs of brain atrophy to neurodevelopmental outcome at 3 y of age. Patients and methods: All preterm infants born in 1997 in our institution with a gestational age <32 wk or birthweight <1500 g were subjected to repeated standardized cranial ultrasound examinations until discharge. Survivors were examined at 3 y of age employing the Bayley Scales of Infant Development II. Results: Eighty‐seven infants were enrolled (birthweight 430–2500 g (median 1200 g), gestational age 24–34 wk (median 29 wk)). Periventricular echodensities were detected in 42 infants (48%); in 12 cases persisting <7 d, in 30 cases >7 d. At discharge, 18 infants (22%) had signs of brain atrophy. Neurodevelopmental outcome was assessed in 64 infants. Infants with signs of brain atrophy scored significantly lower on MDI (atrophy 91.8, no atrophy 101.9; p=0.02), PDI (atrophy 91.4, no atrophy 106.5; p=0.001) and Behaviour Rating Scale (atrophy 41.1, no atrophy 66.4; p=0.01) than infants without atrophy. Periventricular echodensities were not related to outcome. Conclusion: Our data show that infants with sonographic signs of brain atrophy at discharge achieve lower scores in neurodevelopmental testing at 3 y.

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