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. 2024 Apr 18:15:1384678.
doi: 10.3389/fneur.2024.1384678. eCollection 2024.

Neurofilament light chain as a biomarker for acute hepatic porphyrias

Paulo Sgobbi  1 , Paulo de Lima Serrano  1 , Bruno de Mattos Lombardi Badia  1 , Igor Braga Farias  1 , Hélvia Bertoldo de Oliveira  1 , Alana Strucker Barbosa  1 , Camila Alves Pereira  1 , Vanessa de Freitas Moreira  1 , Ícaro França Navarro Pinto  1 , Acary Souza Bulle Oliveira  1 , Wladimir Bocca Vieira de Rezende Pinto  1
Affiliations

Neurofilament light chain as a biomarker for acute hepatic porphyrias

Paulo Sgobbi et al. Front Neurol. .

Abstract

Background: Acute hepatic porphyrias (AHP) represent a rare group of inherited metabolic disorders of heme biosynthesis pathway. This study aims to determine the diagnostic and prognostic value of serum neurofilament light chain (NfL) as potential biomarker for AHP.

Methods: We conducted a cross-sectional observational study to evaluate NfL levels in patients with AHP. They were divided in different groups: normal health individuals; patients with definitive diagnosis of AHP during acute episodes; patients with AHP and infrequent attacks; patients with AHP and recurrent attacks; asymptomatic individuals with positive genetic testing and urinary delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) levels elevated 4 or more times ("high excretors"); asymptomatic individuals with exclusive positive genetic test; control group with Hereditary Amyloidosis related to Transthyretin with Polyneuropathy (ATTRv-PN).

Results: During acute attacks, serum NfL levels were 68 times higher compared to normal controls and disclosed a strong correlation with ALA and PBG levels; also exhibited elevated levels in patients with chronic symptoms regardless of the number of disease attacks compared to healthy controls, and at similar levels to patients with ATTRv-PN, which is a model of progressive neuropathy.

Conclusion: This study represents the first to establish NfL as a biomarker for AHP, disclosing NfL as a sensitive biomarker for axonal damage and chronic symptom occurrence. This study not only underscores that neurological damage associated with the disease in any patient, irrespective of the number of attacks, but also reinforces the progressive and profoundly debilitating nature of acute and chronic symptoms observed in individuals with AHP.

Keywords: acute hepatic porphyria; biomarker; inborn errors of metabolism; inherited metabolic disorders; neurofilament; porphyria.

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Conflict of interest statement

The authors declare that financial support was received from Alnylam Pharmaceuticals for the research, medical writing and/or publication of this article. PS had received funding as scientific advisory member of Alnylam Pharmaceuticals, Biogen, Janssen, and Sanofi. PS had received funding for lectures from Alnylam Pharmaceuticals, Biogen, Novartis, Pfizer, and Sanofi.

Figures

Figure 1
Figure 1
Prevalence of different chronic symptoms in group C.
Figure 2
Figure 2
Prevalence of different chronic symptoms in group D.
Figure 3
Figure 3
Serum neurofilament light chain levels for the different groups. Y axis presents serum levels in pg/mL. Different bar scales are used for group B compared to the other groups.
See this image and copyright information in PMC

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