Acute liver failure (ALF) in infancy and childhood is a life-threatening emergency. Few conditions are known to cause recurrent acute liver failure (RALF), and in about 50% of cases, the underlying molecular cause remains unresolved. Exome sequencing in five unrelated individuals with fever-dependent RALF revealed biallelic mutations in NBAS. Subsequent Sanger sequencing of NBAS in 15 additional unrelated individuals with RALF or ALF identified compound heterozygous mutations in an additional six individuals from five families. Immunoblot analysis of mutant fibroblasts showed reduced protein levels of NBAS and its proposed interaction partner p31, both involved in retrograde transport between endoplasmic reticulum and Golgi. We recommend NBAS analysis in individuals with acute infantile liver failure, especially if triggered by fever.

Mutations in NBAS cause a complex disease with a wide clinical spectrum ranging from isolated RALF to a multisystemic phenotype. Thermal susceptibility of the syntaxin 18 complex is the basis of fever dependency of ALF episodes. NBAS deficiency is the first disease related to a primary defect of retrograde transport. Identification of NBAS deficiency allows optimized therapy of liver crises and even prevention of further episodes.

Cystic pancreatic lesions are common findings in an aging society due to an increasing availability of high-resolution cross-sectional imaging. Although the overall prevalence of malignancy and the rate of malignant conversion are low, especially mucinous pancreatic cystic lesions such as intraductal papillary mucinous neoplasm and mucinous cystic neoplasm harbor significant malignant potential depending on their morphology and size. Recently updated guidelines recommend sophisticated algorithms for initial workup and surveillance based on individual characteristics of the cystic lesion and the patient, thus weighing the lifetime risk for malignancy against the adverse event rate of potentially curative surgery in the light of number and location of cystic lesions, age of the patient, comorbidities, and the resulting life expectancy as well as the effect of repeated follow-up examinations on the patient's quality of life. This article summarizes recommendations from available guidelines and proposes a pragmatic approach to the clinical management of pancreatic cystic lesions.

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