Congenital etiologies of exocrine pancreatic insufficiency

Abstract

Congenital exocrine pancreatic insufficiency is a rare condition. In a vast majority of patients, exocrine dysfunction occurs as part of a multisystemic disease, the most prevalent being cystic fibrosis and Shwachman-Bodian-Diamond syndrome. Recent fundamental studies have increased our understanding of the pathophysiology of these diseases. Exocrine pancreatic dysfunction should be considered in children with failure to thrive and fatty stools. Treatment is mainly supportive and consists of pancreatic enzyme replacement and liposoluble vitamins supplementation.

Keywords: Johanson-Blizzard syndrome; Pearson syndrome; Shwachman-Bodian-Diamond syndrome; cystic fibrosis; exocrine pancreatic insufficiency; pancreas agenesis.

Figure 1

Pathophysiology of exocrine pancreatic insufficiency due to pancreatic exocrine tissue injury. (A) Normal and altered CFTR function. In Class I CFTR mutations, no CFTR protein is synthetized. In Class II, CFTR protein trafficking is defective. Class III mutations lead to impaired gating, whereas Class IV lead to impaired conductance. In Class V and VI, there is, respectively, less CFTR protein or the protein is less stable. (B) Shwachman-Bodian-Diamond type1, type2 and SBDS-like syndromes mainly impact acinar cell function. All disease-causing mutations impact the final maturation steps of ribosome biogenesis. (C) Johanson Blizzard syndrome mainly effects acinar cell function. UBR1 mutations cause defective recognition of misfolded proteins, which can therefore not be degraded by the proteasome. (D) Pearson and Shteyer syndrome lead to mitochondrial dysfunction. Acini seem more affected than ductal cells.