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Neurofilament Light and Its Association With CNS Involvement in Patients With Classic Infantile Pompe Disease
Maarten J Mackenbach1, Eline A J Willemse1, Jan J A van den Dorpel1
1From the Center for Lysosomal and Metabolic Diseases (M.J.M., J.J.A.v.d.D., A.T.v.d.P., J.M.P.v.d.H.), Department of Paediatrics, Erasmus University Medical Center, Rotterdam; Neurochemistry laboratory (E.A.J.W., C.T.), Department of Clinical Chemistry, Amsterdam Neuroscience, Amsterdam University Medical Centres, VU University, the Netherlands; Departments of Biomedizin and Neurology (E.A.J.W.), MS Center and Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), University Hospital Basel and University of Basel, Switzerland; Center for Lysosomal and Metabolic Diseases (N.A.M.E.v.d.B.), Department of Neurology, Erasmus University Medical Center, Rotterdam, the Netherlands; John Walton Muscular Dystrophy Research Centre (J.D.-M.), Newcastle University, United Kingdom; Neuromuscular Disorders Laboratory (J.D.-M.), Institut de recerca de l'hospital de la Santa Creu I Sant Pau, Barcelona; Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER) (J.D.-M.), Madrid, Spain; and Department of Biostatistics & Department of Epidemiology (D.R.), Erasmus University Medical Center, Rotterdam, the Netherlands.
Background And Objectives:
Enzyme replacement therapy (ERT) has substantially improved the outcome of classic infantile Pompe disease, an inheritable muscle disease previously fatal at infancy. However, under treatment, patients develop white matter abnormalities and neurocognitive problems. Therefore, upcoming therapies also target the brain. Currently, biomarkers reflecting CNS involvement are lacking. We aimed to study the association of neurofilament light (NfL) and CNS involvement.
Methods:
To investigate the potential of NfL, we analyzed serum samples of patients with classic infantile Pompe disease who were treated with ERT. The samples were collected at ages of <1, 5, and 10 years, as well as around MRI scans. We compared the outcomes with levels in age- and sex-matched peers. Control samples were originally collected as part of routine blood work in children who underwent small surgeries and stored in the biobank of the Erasmus MC/Sophia Children's Hospital.
Results:
We analyzed 74 serum samples of 17 patients collected at ages ranging from 22 days to 21.2 years (1-8 samples per patient) and compared these with outcomes of 71 matched peers. In the first year of age, NfL levels in patients and controls were similar (10.3 vs 11.0 pg/mL), but mixed linear model analysis showed a yearly increase of NfL of 6.0% in patients, compared with a decrease of 8.8% in controls (p < 0.001). Higher NfL was associated with lower IQ scores (p = 0.009) and lower processing speed scores (p = 0.001).
Discussion:
We found significant differences in NfL levels between patients and controls and a good association between NfL and cognition. NfL deserves further exploration as a biomarker for CNS involvement in patients with classic infantile Pompe disease.
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