[Hereditary hemochromatosis, alpha-1-antitrypsin deficiency and Wilson's disease. Pathogenesis, clinical findings and pathways to diagnosis].
Primary hemochromatosis, alpha-1-antitrypsin (AAT) deficiency, and Wilson's disease are the most common hereditary causes of unclear hepatopathy. Classical primary hemochromatosis (type I) on the basis of a homozygous mutation of the HFE gene, usually presents in adults with increasing hepatocellular siderosis and chronic progressive necroinflammatory liver disease. Homozygous AAT deficiency type PiZZ becomes manifest in newborns as a giant cell hepatitis or findings similar to bile duct atresia, in adults as chronic hepatitis or "cryptogenic cirrhosis". The heterozygous PiZ mutation can lead to PAS-positive hepatocellular AAT deposits increasing over the life time. Immunohistochemical detection of AAT deposits by specific PiZ antibodies is a highly sensitive and specific supplementary method. Molecular analysis of AAT and HFE genes in paraffin-embedded tissue or blood can confirm the diagnosis and allows the zygosity status to be defined. Wilson's disease has to be considered in children and young adults with unexplained histologic findings of chronic hepatitis or steatohepatitis. Rhodanin staining is the most effective histochemical method to detect free copper deposits, but negative staining results do not exclude Wilson's disease. In cases suspected of Wilson's disease further clinical exploration must be initiated. The diagnosis is based on a combination of clinical and biochemical findings, which can be supplemented by mutation analysis of the ATP7B gene.
Zhou
H
H
Pathologisches Institut der Universität Bonn. hui.zhou@ukb.uni-bonn.de
Fischer
H-P
HP
D000251:Adenosine Triphosphatases / Q000235:genetics; D000328:Adult; D027682:Cation Transport Proteins / Q000235:genetics; D002648:Child; D003300:Copper / Q000032:analysis; D000073840:Copper-Transporting ATPases; D003937:Diagnosis, Differential; D006580:Genetic Carrier Screening; D006432:Hemochromatosis / Q000235:genetics* / Q000473:pathology*; D006505:Hepatitis / Q000235:genetics / Q000473:pathology; D006527:Hepatolenticular Degeneration / Q000473:pathology*; D006801:Humans; D008107:Liver Diseases / Q000235:genetics / Q000473:pathology; D009154:Mutation; D011379:Prognosis; D055815:Young Adult; D019896:alpha 1-Antitrypsin Deficiency / Q000473:pathology*
D027682:Cation Transport Proteins; D003300:Copper; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases