TY - JOUR
T1 - Classic infantile Pompe patients approaching adulthood
T2 - a cohort study on consequences for the brain
AU - Ebbink, Berendine J
AU - Poelman, Esther
AU - Aarsen, Femke K
AU - Plug, Iris
AU - Régal, Luc
AU - Muentjes, Carsten
AU - van der Beek, Nadine A M E
AU - Lequin, Maarten H
AU - van der Ploeg, Ans T
AU - van den Hout, Johanna M P
N1 - Funding Information:
Research on Pompe disease at Erasmus MC is also financially supported by ‘Prinses Beatrix Spierfonds’ (project number W.OR13-21, W.OR15-10, W.OR16-07); Tex Net; Sophia Foundation for Medical Research (SSWO) (project number S17-32); Metakids (project number 2016-063); Conselho Nacional de Desenvolvimento Científico e Tecnológico – ‘National Counsel of Technological and Scientific Development’, Brazil (PI); Col-ciencias and Genzyme Corp. BJ Ebbink and JMP van den Hout conceived the study and drafted the article. All authors were involved in conducting the study, analysing and interpreting the data, and critically revising the article. All authors have read and approved the final version of the manuscript. The corresponding author confirms that she had full access to all the data in the
Funding Information:
We would like to thank JC van der Meijden (Erasmus Medical Center Rotterdam) for preparing the figure and David Alexander for his critical review of the article. This project has received funding from the Ministry of Economic Affairs under TKI-Allowance under the TKI-Programme Life Sciences & Health.
Publisher Copyright:
© 2018 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.
PY - 2018/6
Y1 - 2018/6
N2 - 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.
AB - 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.
KW - Adolescent
KW - Age Factors
KW - Brain/diagnostic imaging
KW - Child
KW - Child, Preschool
KW - Cognition Disorders/etiology
KW - Cohort Studies
KW - Disease Progression
KW - Enzyme Replacement Therapy/methods
KW - Female
KW - Glycogen Storage Disease Type II/complications
KW - Humans
KW - Image Processing, Computer-Assisted
KW - Infant
KW - Intelligence/physiology
KW - Magnetic Resonance Imaging
KW - Male
KW - Neuropsychological Tests
KW - Ventilation/methods
UR - http://www.scopus.com/inward/record.url?scp=85044375092&partnerID=8YFLogxK
U2 - 10.1111/dmcn.13740
DO - 10.1111/dmcn.13740
M3 - Article
C2 - 29573408
SN - 0012-1622
VL - 60
SP - 579
EP - 586
JO - Developmental Medicine and Child Neurology
JF - Developmental Medicine and Child Neurology
IS - 6
ER -