遺伝性膵炎

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.

Infantile exocrine pancreatic insufficiency is a rare condition, most often encountered in the context of cystic fibrosis or Shwachman-Diamond syndrome. The SPINK1 gene encodes a trypsin inhibitor protein that prevents the premature activation of digestive enzymes in pancreatic tissue. Heterozygous pathogenic SPINK1 variants are known to predispose individuals to hereditary pancreatitis. We report two cases of severe exocrine pancreatic insufficiency without signs of pancreatitis, caused by the same SPINK1 pathogenic variant in siblings, each presenting with distinct initial clinical manifestations, including one patient with biochemical signs of hepatocellular dysfunction. Patient 1 was enrolled in a rapid whole genome sequencing study, which promptly identified a homozygous loss-of-function variant in SPINK1 (c.27delC). To our knowledge, this specific variant has not been previously reported in association with exocrine pancreatic insufficiency, providing new insights into the disease's pathophysiology. This case also underscores the utility of rapid whole genome sequencing in facilitating timely diagnosis and management.