Obscure pathogenesis of primary iron overload in Indians warrants more focused research

Abstract

Cirrhosis of liver is one of the common clinical conditions encountered in gastroenterology and hepatology practice, and is associated with significant morbidity and mortality. A varied etiology of the condition necessitates detailed history taking, thorough clinical examination as well as a set of laboratory investigations for confirmation. An uncommon etiology of cirrhosis is primary iron overload, generally due to hereditary hemochromatosis for which a high index of suspicion amongst physicians is required for diagnosis. Hereditary hemochromatosis is commonly inherited as an autosomal recessive disorder, leading to progressive iron overload in several organs and eventual iron toxicity. It is caused by an inappropriate increase in iron absorption in the duodenum and upper small intestine due to malfunction of one of the proteins in iron homeostasis. The disease is relatively commonly encountered in the Caucasians and is associated with mutations in the locus, Histone Family E1 (HFE). Among populations of north European origin, two mutations have been identified in the HFE gene, viz. substitution of cysteine for tyrosine at position 282 (C282Y, nucleotide 845) in the alpha 3-domain of the HFE protein and aspartate replacing histidine at amino acid 63 (H63D, nucleotide 187) [1]. The mutation C282Y is the predominant Caucasian mutation with over 90% of patients in north Europe being homozygous for this mutation