Evaluating brain white matter hyperintensity, IQ scores, and plasma neurofilament light chain concentration in early-treated patients with infantile-onset Pompe disease

Yu-Kang Hsu; Yin-Hsiu Chien; Steven Shinn-Forng Peng; Wuh-Liang Hwu; Wang-Tso Lee; Ni-Chung Lee; Eric Po-Yu Huang; Wen-Chin Weng

doi:10.1016/j.gim.2022.10.005

Evaluating brain white matter hyperintensity, IQ scores, and plasma neurofilament light chain concentration in early-treated patients with infantile-onset Pompe disease

Genet Med. 2023 Jan;25(1):27-36. doi: 10.1016/j.gim.2022.10.005. Epub 2022 Nov 18.

Authors

Yu-Kang Hsu¹, Yin-Hsiu Chien², Steven Shinn-Forng Peng³, Wuh-Liang Hwu², Wang-Tso Lee⁴, Ni-Chung Lee², Eric Po-Yu Huang⁵, Wen-Chin Weng⁶

Affiliations

¹ Department of Pediatrics, Taipei City Hospital Renai Branch, Taipei, Taiwan.
² Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan; Department of Pediatrics, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan.
³ Department of Medical Images, National Taiwan University Hospital, Taipei, Taiwan.
⁴ Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan; Department of Pediatrics, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Pediatric Neurology, National Taiwan University Children's Hospital, Taipei, Taiwan.
⁵ Department of Radiology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
⁶ Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan; Department of Pediatrics, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Pediatric Neurology, National Taiwan University Children's Hospital, Taipei, Taiwan. Electronic address: wcweng@ntu.edu.tw.

PMID: 36399131
DOI: 10.1016/j.gim.2022.10.005

Abstract

Purpose: The study aimed to describe central nervous system (CNS) progression in patients with infantile-onset Pompe disease (IOPD) and explore the potential clinical impact and predictors.

Methods: Patients with IOPD treated with enzyme replacement therapy were longitudinally followed with brain magnetic resonance imaging (MRI) and evaluation for IQ scores from 2004 to 2021. Investigation of CNS involvement focused on white matter (WM) abnormalities and was quantified using a scoring system for metachromatic leukodystrophy. MRI scores were correlated with plasma neurofilament light chain (NfL) concentration and IQ scores.

Results: A total of 19 patients who started enzyme replacement therapy at a mean age of 26 days were analyzed; the median age at last examination was 12.1 (range = 1.7-19) years. MRI abnormalities were found in all patients, from supratentorial central WM to U-fibers, then to infratentorial WM, and eventually to gray matter. MRI scores progressed (n = 16) at variable rates (range = 0.8-2.7/y) and were positively correlated with age (n = 16) and negatively correlated with IQ scores (n = 8). Plasma NfL concentration was positively correlated with MRI scores (r² = 0.8569; P < .001; n = 13).

Conclusion: Our results suggest that the progression of CNS involvement in IOPD may be associated with neuroaxonal injury and decreased IQ scores. NfL could serve as a biomarker for CNS involvement in IOPD.

Trial registration: ClinicalTrials.gov NCT02399748.

Keywords: Brain MRI; IQ score; Infantile-onset Pompe disease; Neuroaxonal injury; Neurofilament light chain.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Biomarkers
Brain / diagnostic imaging
Brain / pathology
Child
Child, Preschool
Glycogen Storage Disease Type II* / drug therapy
Glycogen Storage Disease Type II* / pathology
Humans
Infant
Infant, Newborn
Intermediate Filaments
Magnetic Resonance Imaging / methods
White Matter* / diagnostic imaging
Young Adult

Substances

Biomarkers

Associated data

ClinicalTrials.gov/NCT02399748