遺伝性膵炎

Hereditary pancreatitis is a rare genetic disorder, usually associated with gain-of-function mutations in the PRSS1 gene. While in the Indian pediatric population, the SPINK1 mutations are more frequently reported, making PRSS1 mutations, particularly the de novo variants, rare. An 11-year-old school-going Indian girl presented with recurrent acute pancreatitis beginning at the age of 5 years. This progressed to chronic pancreatitis by the age of 10 years. Metabolic, autoimmune, structural, and infectious causes were excluded. The genetic test done revealed a heterozygous pathogenic PRSS1 c.86A>T (p.Asn29Ile) variant. In the absence of family history, this was consistent with a likely de novo mutation. No pathogenic variants were detected in SPINK1, CFTR, CTRC, or CPA1. Pancreatic enzyme replacement therapy and dietary modification reduced the frequency of attacks and preserved her growth. This case highlights the importance of genetic evaluation in children who present with unexplained recurrent pancreatitis, even when there is no positive family history. Early identification of PRSS1 mutation allows for appropriate counseling, long-term surveillance, and complication prevention.

OBJECTIVES: CPRSS1-associated hereditary pancreatitis in children is characterized by early onset and rapid progression to chronic disease; however, data from Eastern European populations remain limited. This study aimed to evaluate disease severity, recurrence burden and progression to chronic pancreatitis in a Romanian pediatric cohort with PRSS1-associated hereditary pancreatitis. MATERIALS AND METHODS: We conducted a retrospective observational study that included pediatric patients with pathogenic or likely pathogenic PRSS1 mutations. Clinical variables analyzed comprised age at onset, number of acute pancreatitis episodes, disease severity, complications and progression to chronic pancreatitis. Descriptive statistics were used. RESULTS: Five pediatric patients were included. All subjects developed recurrent acute pancreatitis. Patients with severe disease exhibited a higher recurrence burden compared to those with mild disease. Progression to chronic pancreatitis occurred in 80% of cases. Structural pancreatic changes and local complications were frequently observed. CONCLUSIONS: PRSS1-associated hereditary pancreatitis in children is characterized by early onset, high recurrence burden and frequent progression to chronic disease. Disease severity appears to be associated with recurrence burden, suggesting a more aggressive clinical phenotype in affected patients.

Background/Objectives: Endoscopic retrograde cholangiopancreatography (ERCP) in children with acute or chronic pancreatitis, or following pancreatic trauma, is technically demanding and may be associated with an increased risk of complications. Evidence on technical success and complication rates in preadolescent children is limited. This study aimed to evaluate the short- and long-term outcomes of ERCP with pancreatic stenting in children with pancreatic conditions. Methods: In this retrospective single-center cohort study, consecutive patients aged ≤12 years who underwent ERCP with pancreatic stenting for acute or chronic pancreatic diseases or pancreatic trauma were included. Demographic, clinical, and procedural data were collected, and complications and clinical response, were assessed. Results: A total of 20 patients (mean age 7 years, range 2-12; 45% female) underwent 62 ERCP procedures for pancreatic indications. Nine patients (45%) had a known genetic mutation. Post-ERCP pancreatitis occurred in 2 procedures (3.2%), and bleeding in 1 procedure (1.6%). No perforations or procedure-related mortality were observed. Technical success was achieved in 57/62 procedures (91.9%), with associated improvement in symptoms, pain, or inflammatory markers. Conclusions: In this pilot study from Sweden, ERCP with pancreatic stenting appears to be a feasible therapeutic option in pre-teen children with pancreatic diseases, with a good technical success rate and relatively low complication rates. Further studies are warranted to better define long-term outcomes in this population.

BACKGROUND: Hereditary pancreatitis is a rare type of chronic pancreatitis that is due to an inherited germline mutation, involving pancreatic trypsin activity. This condition causes either increased trypsinogen activation or impaired trypsin inhibition/degradation, resulting in recurrent pancreatic injury and progression to chronic pancreatitis. CASE PRESENTATION: We present the case of a young male who presented with acute pancreatitis in the setting of a positive family history of chronic pancreatitis. He had no prior similar episodes. Imaging revealed features consistent with chronic calcific pancreatitis, including diffuse dilation of the main pancreatic duct with intraductal stones. The patient underwent ERCP with pancreatic sphincterotomy and successful removal of multiple pancreatic stones resulting in symptomatic relief. Genetic testing confirmed the diagnosis of hereditary pancreatitis with identification of a pathogenic PRSS1 mutation. MANAGEMENT: Therapeutic interventions typically involve management of acute pancreatitis flares and its complications, chronic pain management, exocrine and endocrine insufficiency, and endoscopic and surgical interventions, and genetic counseling and surveillance. CONCLUSION: Our case report emphasizes the significance of taking hereditary pancreatitis into account in acute-on-chronic presentations. This helps in establishing a genetic diagnosis for directing treatment, long-term surveillance, and family screening.

OBJECTIVES: PRSS1-associated hereditary pancreatitis (HP) is a rare autosomal dominant disorder characterized by early disease onset. Although PRSS1 variants are recognized as pathogenic factors, the epidemiology and clinical phenotype of PRSS1 hereditary pancreatitis remain inconsistently reported. This systematic review consolidates current evidence to define the genetic landscape, clinical profile, and implications for diagnosis and management. METHODS: Following PRISMA guidelines, MEDLINE, EMBASE, and Cochrane CENTRAL were searched on January 6, 2025. All observational studies reporting genetic, clinical, or pain outcomes in PRSS1-associated hereditary pancreatitis were included. Methodological quality was appraised using Joanna Briggs Institute tools, and data were synthesized narratively due to study heterogeneity. RESULTS: Sixty-eight studies from multiple countries met the inclusion criteria. Over 70% of individuals with PRSS1-associated HP presented before age 18, indicating early-onset disease. Pain and reduced quality of life were the most frequently reported clinical features, although assessment methods varied and validated instruments were used in only a few studies. Diabetes prevalence ranged from minimal in children to 14%-26% in adults, with inconsistent reporting of diabetes type. PRSS1 R122H and N29I were the most common pathogenic variants, with additional pathogenic, benign, unknown, and variants of uncertain significance also reported. Pancreatic cancer was rarely documented, despite the elevated lifetime risk in this cohort. CONCLUSIONS: PRSS1-associated HP is characterized by early disease onset and a substantial pain burden, but clinical reporting remains inconsistent. Standardized outcome measures and longitudinal multicenter studies are needed to improve comparability and prognostic insight.