The clinical and genetic features of hereditary pancreatitis in South Australia

Abstract

Objective To characterise the clinical phenotypes and genetic variants of hereditary pancreatitis in people diagnosed in South Australia. Design, setting, participants Cross‐sectional study of people who received molecular diagnoses of hereditary pancreatitis from one of four major diagnostic services in South Australia, 1 January 2006 – 30 June 2021. Main outcome measures Genotypic and clinical features of people with hereditary pancreatitis, including age at onset, attack frequency, pain indices, use of opioid medications, and physical and mental health impact of hereditary pancreatitis. Results We identified 44 people from ten families who received molecular diagnoses of hereditary pancreatitis during 2006–21 (including 25 Indigenous people [57%] and 27 women [61%]): 36 with PRSS1, five with SPINK1, and three with PRSS1 and SPINK1 mutations (determined by whole exome sequencing). Symptom onset before the age of ten years was reported by 37 people (84%). Pancreatitis‐related pain during the preceding four weeks was described as moderate or high by 35 people (79%); 38 people regularly used opioids (86%). Fifteen patients had diabetes mellitus (34%), and eight had undergone pancreatic surgery (18%). The estimated prevalence of hereditary pancreatitis was 1.1 (95% CI, 0.72–1.4) cases per 100 000 population for non‐Indigenous and 71 (95% CI, 66–77) cases per 100 000 population for Indigenous South Australians. Among people with adult‐onset chronic pancreatitis admitted to South Australian public hospitals during 2001–2019, the proportions of Indigenous people (12%) and women (38%) were smaller than we report for hereditary pancreatitis. Conclusion The estimated prevalence of hereditary pancreatitis in South Australia is higher than in Europe. PRSS1 gene mutations are important causes, particularly among Indigenous young people.

Surgical and Endoscopic Intervention for Chronic Pancreatitis in Children: The Kings College Hospital Experience

“…Genetic mutations (Table 1) seem to account for the majority of such cases [1,4,5] where an actual aetiology can be defined. This dates from 1996 and a report by Whitcomb et al [6] that identified mutations in PRSS1 (Protein Serine type 1) in families from Kentucky and West Virginia who had children and young adults with CP, which was later confirmed in other studies [1,7,8]. Since then, other genes have been identified, including SPINK1 (serine protease inhibitor kazal type 1) [1,[9][10][11], CFTR (cystic fibrosis transmembrane conductance regulator) [12][13][14], CPA1 (carboxypeptidase A1) [15], CTRC (chymotrypsin C) [5,[16][17][18], CLND2 (claudin-2) [19], and perhaps CELA3B (chymotrypsin-like elastase family member 3B) [20].…”

“…Genetic mutations (Table 1) seem to account for the majority of such cases [1,4,5] where an actual aetiology can be defined. This dates from 1996 and a report by Whitcomb et al [6] that identified mutations in PRSS1 (Protein Serine type 1) in families from Kentucky and West Virginia who had children and young adults with CP, which was later confirmed in other studies [1,7,8]. Since then, other genes have been identified, including SPINK1 (serine…”

“…These children are probably best labelled as having hereditary pancreatitis (HP), though many may have a de novo presentation. The spectrum of clinical features varies considerably, but there appears to be no gender disparity [8,21]. A summary of the actual mechanisms of such genetic mutations is given in Table 1.…”