Neurofilament Light Chain as an Indicator of Neurological Damage in Acute Hepatic Porphyria

A recent cross-sectional observational study found that serum neurofilament light chain (NfL) levels are elevated in individuals with acute hepatic porphyria (AHP), particularly during acute episodes.

Patients with AHP experiencing acute attacks had NfL levels that were 68 times higher than those of healthy controls, and NfL elevation correlated closely with increased levels of delta-aminolevulinic acid (ALA) and porphobilinogen (PBG). Additionally, chronic elevation of NfL was noted in individuals with recurrent attacks or persistent symptoms, suggesting that NfL could serve as a biomarker for axonal damage in both acute and chronic AHP presentations.

AHP is a rare, inherited metabolic disorder affecting the heme biosynthesis pathway, often resulting in severe neurological symptoms. This study was conducted to assess the potential of NfL as a biomarker for AHP, given the need for reliable markers to evaluate neurological damage and disease progression in these patients. By examining NfL levels, the study aimed to determine whether this biomarker could help in diagnosing and monitoring AHP-related neurological involvement.

In this study, researchers compared NfL levels across several groups: individuals with AHP experiencing acute attacks, those with infrequent or recurrent attacks, and asymptomatic individuals who either tested positive for AHP-associated gene mutations or had elevated urinary ALA and PBG levels (“high excretors”). The study also included a healthy control group and a group of patients with hereditary transthyretin amyloidosis polyneuropathy (ATTRv-PN), a model of progressive neuropathy. Serum NfL levels were analyzed and compared across these groups, and associations between NfL, ALA, and PBG levels were assessed to better understand the extent of neurological damage in AHP.

The results showed not only the 68-fold increase in NfL levels during acute attacks (P < .001), but also elevated NfL levels in patients with chronic symptoms, regardless of attack frequency, and these levels were comparable with those in patients with ATTRv-PN. In asymptomatic high excretors, NfL levels were also elevated compared with healthy controls, indicating possible subclinical axonal damage in these individuals.

This study is limited by its cross-sectional design, which restricts the ability to observe changes in NfL over time or its relationship to clinical outcomes and treatment effects. The small sample size for certain subgroups also limits the findings across the diverse AHP patient population.

“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,” the study authors concluded. “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.”

Reference

Sgobbi P, Serrano PL, Badia BML, et al. Neurofilament light chain as a biomarker for acute hepatic porphyrias. Front Neurol. 2024;15:1384678. doi:10.3389/fneur.2024.1384678.