title: Hepatitic inherited metabolic disorders.
abstract: Primary metabolic disorders are a disparate group of diseases that may or may not be accompanied by hepatic manifestations. Those with liver involvement may show a range of histopathologic changes. Proper histologic diagnosis requires correlation with clinical and laboratory data, including evaluation for mutations either via serum protein electrophoresis or through formal genetic analysis. This article is a review of the three most common inherited metabolic disorders which may present with a hepatitic pattern. In alpha1-antitrypsin disorder, there is a broad range of clinical presentations, age at presentation, and histological features ranging from "neonatal hepatitis" to a chronic progressive hepatitis in later childhood and adulthood. Hence, this disorder must be in the differential diagnosis of liver disease of the very young, and in older children and adults, with or without coexistent overt pulmonary symptoms. In Wilson disease, presentation tends to be in older childhood or the adult, with a progressive chronic hepatitis. Cystic fibrosis may feature a characteristic obstructive biliary syndrome, coexisting with the many extrahepatic manifestations of this debilitating disease. Lastly, the progressive familial intrahepatic cholestasis (PFIC) syndromes are given as examples of inherited metabolic conditions in which relentlessly progressive cholestatic liver disease eventuates over years in end-stage cholestatic liver disease with cirrhosis. Distinguishing features include absence of elevated serum gamma-glutamyl transpeptidase (GGT) in PFIC-1 and PFIC-2, and elevated GGT in PFIC-3. However, molecular studies are required for a confident diagnosis of the rare PFIC syndromes.
authors.affiliation: University of Florida College of Medicine, Gainesville, Florida 32610-0275, USA.
authors.forename: May
authors.initials: M
authors.lastname: Arroyo
authors.forename: James M
authors.initials: JM
authors.lastname: Crawford
mesh_terms: D002780:Cholestasis, Intrahepatic; D003550:Cystic Fibrosis; D006527:Hepatolenticular Degeneration; D006801:Humans; D008661:Metabolism, Inborn Errors / Q000150:complications*; D000515:alpha 1-Antitrypsin
chemical_list: D000515:alpha 1-Antitrypsin