Neurofilament light chain (NfL) may serve as a biomarker for central nervous system involvement in infantile-onset Pompe disease (PD), as evidence suggests that nervous system progression could be associated with structural brain abnormalities, including neuroaxonal damage, according to a recently published study in Genetics in Medicine.

Enzyme replacement therapy (ERT) has successfully increased survival in patients with infantile-onset PD. However, increasing evidence suggests that patients with prolonged survival could experience central nervous system involvement leading to cognitive dysfunction, Yu-Kang Hsu, of the Taipei City Hospital Renai Branch in Taiwan, and colleagues noted.

Postmortem findings revealed glycogen accumulation in the brain cells of patients with infantile-onset PD, the study authors noted. Furthermore, magnetic resonance imaging (MRI) studies report structural brain abnormalities associated with age, they added.

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Given modern measuring techniques, blood NfL levels have been used as an unspecific marker of axonal damage in recent years. The authors hypothesize that NfL could predict the severity of white matter (WM) in patients with infantile-onset PD.

The prospective cohort study included 19 patients with infantile-onset PD receiving ERT. All patients were longitudinally followed with MRI studies every 1 to 3 years for approximately 12 years. Cognitive function was assessed through standardized IQ tests and correlated with imaging. NfL blood levels were measured in 17 patients in their last check-up and were also correlated with imaging.

The authors used an MRI scoring system based on the location and extent of WM lesions as well as the presence of atrophy. Higher scores were indicative of extensive damage.

All patients presented with structural brain abnormalities in MRI. Brain lesions had a characteristic pattern associated with age. Most patients had central WM involvement at the median age of 3 years. They then had internal capsules at 9 years of age and corpus callosum and infratentorial WM at 11 years of age. MRI scores were directly correlated with age.

IQ examination scores ranged from low to high average. The authors noted that all but 1 patient presented a decrease in their IQ scores correlated with age and MRI scoring. The NfL concentration was measured in 17 patients; all of them had significantly higher levels than healthy controls. Notably, NfL correlated strongly with MRI scores.

“Our study highlights the urgent need to develop therapies targeting neurodegeneration in Pompe disease,” the authors wrote. “Furthermore, neuroimaging quantification tools and plasma NfL concentration may be a promising biomarker for monitoring CNS progression and patient response to treatment in future trials.”


Hsu Y-K, Chien Y-H, Shinn-Forng Peng S, et al. Evaluating brain white matter hyperintensity, IQ scores, and plasma neurofilament light chain concentration in early-treated patients with infantile-onset Pompe disease. Genet Med. Published online November 17, 2022. doi:10.1016/j.gim.2022.10.005