Severe CNS involvement in a subset of long-term treated children with infantile-onset Pompe disease

Daniel Kenney-Jung; Aditi Korlimarla; Gail A. Spiridigliozzi; Walter Wiggins; Michael Malinzak; Gretchen Nichting; Seung-Hye Jung; Angela Sun; Raymond Y. Wang; Aisha Al Shamsi; Chanika Phornphutkul; James Owens; James M. Provenzale; Priya S. Kishnani

doi:10.1016/j.ymgme.2023.108119

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Severe CNS involvement in a subset of long-term treated children with infantile-onset Pompe disease

Journal article

Peer reviewed

Severe CNS involvement in a subset of long-term treated children with infantile-onset Pompe disease

Daniel Kenney-Jung, Aditi Korlimarla, Gail A. Spiridigliozzi, Walter Wiggins, Michael Malinzak, Gretchen Nichting, Seung-Hye Jung, Angela Sun, Raymond Y. Wang, Aisha Al Shamsi, …

Molecular genetics and metabolism, Vol.141(2), 108119

02/01/2024

DOI: 10.1016/j.ymgme.2023.108119

PMCID: PMC11080415

PMID: 38184429

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Abstract

The standard of care for patients with infantile-onset Pompe disease (IOPD) is enzyme replacement therapy (ERT), which does not cross the blood brain barrier. While neuromuscular manifestations of IOPD are well-described, central nervous system (CNS) manifestations of this disorder are far less characterized. Here we describe severe CNS-related neurological manifestations including seizures and encephalopathy in six individuals with IOPD. We identified six children with IOPD who developed CNS manifestations such as seizures and/or encephalopathy. We studied their brain magnetic resonance imaging scans (MRIs) and graded the severity of white matter hyperintensities (WMHI) using the Fazekas scale scoring system as previously published. Longitudinal cognitive measures were available from 4/6 children. All six IOPD patients (4 males/2 females) had been treated with ERT for 12–15 years. Seizures and/or encephalopathy were noted at a median age at onset of 11.9 years (range 9–15 years). All were noted to have extensive WMHI in the brain MRIs and very high Fazekas scores which preceded the onset of neurological symptoms. Longitudinal IQ scores from four of these children suggested developmental plateauing. Among a subset of IOPD patients on long-term ERT, CNS manifestations including hyperreflexia, encephalopathy and seizures may become prominent, and there is likely an association between these symptoms and significant WMHI on MRI. Further study is needed to identify risk factors for CNS deterioration among children with IOPD and develop interventions to prevent neurological decline.

Epilepsy

Case series

Pompe disease

White matter disease

Details

Title: Subtitle: Severe CNS involvement in a subset of long-term treated children with infantile-onset Pompe disease
Creators: Daniel Kenney-Jung - Duke Medical Center
Aditi Korlimarla - Duke Medical Center
Gail A. Spiridigliozzi - Duke Medical Center
Walter Wiggins - Duke University Hospital
Michael Malinzak - Duke University Hospital
Gretchen Nichting - Duke Medical Center
Seung-Hye Jung - Duke Medical Center
Angela Sun - Seattle Children's Hospital
Raymond Y. Wang - Children's Hospital of Orange County
Aisha Al Shamsi - Tawam Hospital
Chanika Phornphutkul - Brown University
James Owens - Seattle Children's Hospital
James M. Provenzale - Duke University Hospital
Priya S. Kishnani - Duke Medical Center
Resource Type: Journal article
Publication Details: Molecular genetics and metabolism, Vol.141(2), 108119
DOI: 10.1016/j.ymgme.2023.108119
PMID: 38184429
PMCID: PMC11080415
NLM abbreviation: Mol Genet Metab
ISSN: 1096-7192
eISSN: 1096-7206
Publisher: Elsevier Inc
Language: English
Date published: 02/01/2024
Academic Unit: Stead Family Department of Pediatrics; Neurology (Pediatrics)
Record Identifier: 9984701750102771

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