Genetic and Electrophysiological Characterization of Acute Recurrent Pancreatitis in Israeli Patients

Genetics is a significant contributor to acute recurrent pancreatitis. This study evaluates the prevalence of genetic variants and assesses electrophysiological characteristics in Israeli patients.

Patients with ≥2 episodes of acute pancreatitis, no history of drug use, normal IgG4 levels, and normal cholangiopancreatographic findings were included. Genetic analysis targeted the PRSS1, SPINK1, CTRC, CFTR, CPA1 , and TRPV6 genes, as well as the CEL-HYB1 allele. Sweat testing and nasal potential difference measurements were also performed.

Seventy-nine patients (median age: 13 y; range: 2-61) were referred between 2015 and 2021. Forty-five (57.0%) carried at least one genetic variant; 18 patients carried 2 or more variants. CFTR variants were the most common (35.4%), followed by PRSS1 (11.4%), SPINK1 (10.1%), and CTRC (10.1%). The rare PRSS1 p.Lys23Arg variant was prevalent among Jewish Georgian patients (n=8). Patients with genetic variants were younger than those without ( P <0.0035). Of the 71 patients who underwent nasal potential difference testing, 2 (5.6%) had abnormal results. Sweat test in 66 patients showed a mean value of 36 ± 16 mmol/L; 6 had results above 60 mmol/L; 2 of these carried CFTR variants TG[11]T[5] and p.Leu997Phe but had normal nasal potential.

More than half of acute recurrent pancreatitis cases had a genetic basis, presenting at a younger age. CFTR variants were the most prevalent. The high prevalence of the PRSS1 p.Lys23Arg variant among Jewish Georgian individuals suggests a potential founder effect. These findings highlight the importance of genetic evaluation in the diagnosis and management of acute recurrent pancreatitis.