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There is a growing list of genetic diseases caused by defects of one of the members of the ATP binding cassette (ABC) transporter superfamily.1 ABC transporters mediate the energy dependent transport of peptides, steroid hormones, and drugs and their metabolites across membranes, not only in mammals but also in fish, bacteria, worms, and even plants. ABC transporters are important in almost every human cell or organ and therefore the spectrum of diseases caused by defects of these proteins is diverse and includes: liver diseases (progressive familial intrahepatic cholestasis,2cystic fibrosis,3 Zellweger syndrome,4adrenoleuko- dystrophy,5 and Dubin-Johnson syndrome6); eye disorders (Stargardt disease,7 autosomal recessive retinitis pigmentosa,8 and cone-rod dystrophy9); disorders of cholesterol metabolism (familial HDL deficiency10 and Tangier disease10); and diseases of carbohydrate metabolism (familial persistent hyperinsulinaemic hypoglycaemia of infancy11).
Progressive familial intrahepatic cholestasis type 1
Progressive familial intrahepatic cholestasis (PFIC) belongs to a group of autosomal recessive diseases characterised by cholestasis starting in infancy (table 1). PFIC type 1 or Byler disease often begins with recurrent episodes of intrahepatic cholestasis progressing to permanent cholestasis with fibrosis, cirrhosis, and liver failure necessitating liver transplantation in the first decade of life.2 ,12-14 Children with PFIC are small for their age and, in addition to cholestasis and pruritus, they sometimes have diarrhoea, pancreatitis, and hearing loss.15 The larger bile ducts are anatomically normal and histologically the liver shows a picture of bland canalicular cholestasis without much bile duct proliferation, inflammation, fibrosis, or cirrhosis.14 ,16On electron microscopy there is a paucity of canalicular microvilli and a thickened pericanalicular network of microfilaments with coarse granular bile called “Byler bile” in the canaliculi. Characteristically serum gamma-glutamyltransferase (gamma-GT) activity is not increased or only slightly elevated while parameters of cholestasis such as alkaline phosphatase …
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