Zusammenfassung
Unter den genetischen Hämochromatosen hat nur der autosomal-rezessiv vererbte Typ 1 eine klinische Bedeutung. Hier führt die homozygote Punktmutation C282Y im HFE-Gen zu einer erhöhten intestinalen Eisenresorption und somit im Verlauf von Jahrzehnten zu Eisenablagerung und Schädigung verschiedener Organe (Leber, Pankreas, Herz, Gelenke, Gonaden u. a.). In Populationen keltischer Abstammung ist die Typ-1-Hämochromatose die häufigste vererbte Stoffwechselerkrankung. Die Häufigkeit homozygoter Merkmalsträger liegt bei 0,5%. Aufgrund einer inkompletten Penetranz liegt die Häufigkeit der klinischen Erkrankung nur bei etwa 0,1%. Die Diagnostik der Hämochromatose basiert auf der Bestimmung von Transferrinsättigung und Serumferritin, wobei die Transferrinsättigung sensitiver und spezifischer ist; der Gentest kann die Diagnose sichern. Eine Leberbiopsie wird nur noch bei Ferritinwerten >1000 ng/ml mit der Fragestellung Leberzirrhose empfohlen. Die Aderlasstherapie sichert eine normale Prognose, wenn sie vor dem Auftreten von Leberzirrhose und Diabetes begonnen wird. Zukünftige Anstrengungen müssen deshalb der Früherkennung gelten.
Abstract
Among the conditions known as hereditary hemochromatosis, only the autosomal recessive type 1 has any clinical significance. In this case a homozygote point mutation C282Y in the HFE gene leads to increased intestinal iron resorption and over the course of decades to iron deposition and injury to various organs (e.g. liver, pancreas, heart, joints and gonads). In populations of Celtic descent, type 1 hemochromatosis is the most common hereditary metabolic disease. The frequency of homozygote carriers is approximately 0.5% but because of an incomplete penetrance, the frequency of clinical diseases is only approximately 0.1%. The diagnosis of hemochromatosis is based on determination of transferrin saturation and serum ferritin levels, whereby transferrin saturation is more sensitive and specific. The diagnosis can be confirmed with genetic testing. A liver biopsy is only recommended by ferritin values of >1,000 ng/ml to evaluate the degree of liver fibrosis. Therapeutic phlebotomy ensures a normal prognosis if initiated before the occurrence of liver cirrhosis and diabetes. Therefore future efforts should be dedicated to early recognition.
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Niederau, C. Genetische Hämochromatose. Gastroenterologe 3, 199–211 (2008). https://doi.org/10.1007/s11377-008-0146-5
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DOI: https://doi.org/10.1007/s11377-008-0146-5