Objective:

To evaluate whether blood ELP1 levels correlate with sensory and motor nerve function and could serve as a biomarker.

Background:

Familial dysautonomia (FD) is an inherited sensory and autonomic neuropathy with significant phenotypic variability and decreased levels of elongator protein 1 (ELP1). We hypothesize that patients with higher levels of normal wild-type ELP1 would present a milder phenotype.

Design/Methods:

We conducted a retrospective cross-sectional study of 125 participants, including 59 FD patients homozygous for the founder mutation and 66 heterozygous carriers. We developed a specific radioimmunoassay (RIA) for measuring ELP1 levels in blood. Sensory function was assessed using quantitative sensory testing (QST) and nerve conduction velocities (NCV). We measured cold, warm, and vibration detection thresholds and ELP1 levels in 120 FD patients, with repeat ELP1 levels taken one year later in a subset of 22 participants to assess reproducibility.

Results:

The average ELP1 levels in FD patients were significantly lower than in carriers (244 ± 75 vs. 2210 ± 1031 pg/ml, p < 0.001). Higher ELP1 levels were significantly correlated with lower sensory thresholds for warm (r = 0.366, p = 0.04), cold (r = 0.496, p = 0.01), and vibration thresholds (r = 0.550, p < 0.001) and with higher amplitudes of sensory nerve action potential (SNAP) in the median nerve (r = 0.550, p < 0.001), suggesting a role for ELP1 in preserving sensory nerve integrity. No correlation was found between motor conduction velocities and ELP1 levels, which may reflect the differential impact of FD on sensory versus motor neurons. Test-retest reproducibility of ELP1 measurements demonstrated high reliability (R² = 0.827, p < 0.001).

Conclusions:

Blood ELP1 levels appear stable over time and are significantly associated with sensory nerve function in patients with FD, making ELP1 a potential biomarker for monitoring disease severity and a marker of target engagement in clinical trials.