Work

The clinical utility of neurofilament light chain for early detection and prediction of disease burden and severity in neuronopathic Gaucher disease

Year: 2025

Type: article

Abstract: Newborn screening, while enabling early diagnosis, poses challenges to correctly identifying and typing otherwise asymptomatic infants with neuropathic Gaucher disease (nGD). Glucosylsphingosine (Lyso-GL1) may be elevated at birth, but it does not help differentiate between nGD types. Neurofilament light chain (NfL), a neuronal cytoplasmic protein, is a marker for axonal damage and is associated with elevated levels in cerebrospinal fluid (CSF) and blood in lysosomal disorders characterized by neurodegeneration. In a prospective study (NCT02000310, 13-CFCT-07), NfL and Lyso-GL1 levels were assessed along with other neurological indicators in 35 GD patients (ages 6 months to 72 years: 8 GD1, 7 GD2, 20 GD3). Eighteen patients with other LSDs-with or without neurodegeneration-served as controls. In GD2, Lyso-GL1 was markedly elevated (range: 105-457 ng/mL), and all GD2 patients with neurological manifestations had elevated NfL. In GD3, Lyso-GL1 levels were highly variable, reflecting the clinical heterogeneity. NfL was elevated in 4 of 20 GD3 patients, all of whom had clinically discernable neurological involvement. All GD1 patients had normal NfL levels (max: 0.9 (ref:<1.63)) and near-normal Lyso-GL1 (maximum pretreatment: 10). Clinically, an abnormal Auditory Brainstem Response (ABR) correlated with neurodegeneration. ABR was abnormal in all GD2 infants tested, while 65 % (13/20) of GD3 patients had normal auditory function. The combination of elevated NfL and Lyso-GL1 levels, along with abnormal ABR, can aid in the early identification of severe nGD-even in the absence of characteristic neurological symptoms-supporting the need for earlier diagnosis and timely clinical intervention.

Source: Molecular Genetics and Metabolism

DOI: 10.1016/j.ymgme.2025.109181

Authors: Leah Svarny, Arooj Agha, Julia Dao, Bobby Sandhu, Margarita Ivanova, Ozlem Goker-Alpan

Institution: Lysosomal and Rare Disorders Research and Treatment Center

Language: English

Topic: Lysosomal Storage Disorders Research

Subfield: Physiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,680