Diagnosis of Hereditary Haemochromatosis using Non-Invasive Methods

Abstract

Hereditary (idiopathic, genetic) haemochromatosis is a genetic disease in which food iron absorption is inadequately increased and not balanced to the body iron stores. As a consequence, untreated patients have a risk to develop iron overload which can give rise to various iron-induced organ damages, leading in some cases to multi-organ dysfunction (liver cirrhosis, diabetes, cardiomyopathy). Diagnosis in this iron loading disease was formerly based on highly increased transferrin saturations, elevated serum ferritin concentrations and on excessive iron deposits in biopsy material from liver. After the identification of the HFE gene and its most common mutations, a genetic diagnosis independent from iron stores has become available. Because of individual variations in the loading process, diagnostic criteria are still necessary to characterise the risks of a given patient to develop iron-induced lesions and clinical symptoms. This review describes the current knowledge of the molecular pathology and discusses criteria for diagnosis and screening of hereditary haemochromatosis. Non-invasive liver iron quantification could represent the optimal complement to the HFE gene testing. Data on our experience with SQUID biosusceptometry, which makes liver biopsy unnecessary in most cases, are presented.

Liver Iron Susceptometry

“…Besides the HFE-1 gene related hemochromatosis, there are other genetic forms (HFE types 2-4) more prevalent in Southern Europe (Roetto and Camaschella, 2005) and in populations of African origin (Gordeuk et al, 2003). Beyond initial blood parameter tests (serum iron, transferrin saturation, ferritin) and genotyping, the definitive test for the diagnosis of PH is the quantitative assessment of liver iron either by biopsy or noninvasive methods (Nielsen et al, 2003a).…”

“…BLS is successful in identifying those patients really afflicted by the disease (Nielsen et al, 2003a). LICs > 1000 mg g À1 liver were detected in 30% of these patients.…”

Monitoring Long‐Term Efficacy of Iron Chelation Treatment with Biomagnetic Liver Susceptometry

“…In Table 1, the recommended ranges for the treatment of thalassemia are given for the most typical conversion factors. In addition, the maximum LIC as measured by SQUID BLS in heterozygotes for hereditary hemochromatosis24 and the lower LIC threshold for development of progressive liver fibrosis in hepatitis C virus‐negative thalassemia patients after bone marrow transplantation are given 25…”