HEREDITARY HEMOCHROMATOSIS - RECENT ADVANCES IN MOLECULAR-GENETICS AND CLINICAL MANAGEMENT

Background and Objective. Hereditary hemochromatosis (HC) is an inborn error of iron metabolism leading to increased intestinal iron absorpt ion and progressive iron overload. There have been definite advances i n our knowledge of the pathogenesis and management of idiopathic hemoc hromatosis in recent years, which prompted us to review this subject. Information sources. The material examined in the present review inclu des articles and abstracts published in the journals covered by the Sc ience Citation Index(R) and Medline(R). In addition, both authors have been working in this field for several years and have contributed twe lve of the papers cited in the references. State of art and Perspectiv es. The disease is a late onset autosomic recessive condition, especia lly frequent in Caucasians. if unrecognized, severe clinical symptoms develop in mid-life related to organ failure. Early diagnosis prevents complications, since an intensive phlebotomy course removes excess ir on and offers patients a normal life expectancy. Transferrin saturatio n is the first examination step, but liver biopsy is still essential f or diagnosis and prognosis of HC. The biochemical defect is unknown. P ositional cloning of the HC gene has led to the isolation of all the c andidate region on the short arm of chromosome 6, telomeric to HLA-A. Recently a putative HC gene has been cloned from this region and found to be mutated in a large proportion of patients. The gene, known as H LA-H, is an atypical MHC class I gene. Although its biological functio n remains unknown, HLA-H is the first strong HC candidate gene. Molecu lar screening of patients and carriers is now possible in a significan t portion of cases, thereby permitting better control of the disease. If it is unequivocally confirmed that the HLA-H gene is responsible fo r the disease, understanding of its biological function will provide i nformation on the type and activity of the involved protein, revealing new insights into iron uptake and metabolism in humans. (C) 1997, Fer rata Storti Foundation.