Heredity of idiopathic haemochromatosis: A study of 106 families

Abstract

More than 80 % of the first degree relatives of 106 patients with iron overload ‐ 97 with idiopathic haemochrornatosis (I.H.) and nine with haemosiderosis secondary to alcohol induced liver disease (A.H.) ‐ were examined. Physical examination and measurement of plasma iron level and UIBC were done in all subjects; relatives who presented with some anomaly were submitted to a desferrioxamine test and, if the latter showed a high urinary iron output, to a liver biopsy. While absent in relatives of A.H. patients, iron overload was present in 78 out of 499 relatives of I.H. patients: 29 major and 49 minor forms. The major forms involved the sibships almost exclusively. The genetic analysis showed much evidence in favour of a recessive or rather intermediate form of inheritance, with heterozygous developing minor forms. However, other modes of transmission, especially poly‐genic (probably oligogenic), cannot be totally excluded. Data from recent studies showing a strong correlation between I.H. and certain HLA antigens do not conflict with the above conclusions.

Genetics, Genetic Testing, and Management of Hemochromatosis: 15 Years Since Hepcidin

“…After the description of "bronze diabetes and pigmented cirrhosis" by French physicians in the mid-1800s 2, 3 , the term hemochromatosis (introduced in 1889 to generically describe the bronze stain of organs due blood-borne pigments 4 ) was later generally referred to a variety of iron-loading conditions and attributed to diabetes, hemolysis, alcohol, toxins, or metabolic disturbances. Joseph Sheldon was the first to suggest in 1935 that the disease "hemochromatosis" resulted from an inherited metabolic defect 5 , whereas Marcel Simon linked the syndrome to the Major Histocompatibility Complex on chromosome 6 6 , where one of the major hemochromatosis genes, HFE, was eventually identified in 1996 7 . Yet, even after this seminal discovery, our understanding of the essence of hemochromatosis as a unique and distinct syndromic entity and the comprehension of its pathogenic basis have been far from being clarified.…”

Idiopathic Hemochromotosis and Alpha-1-Antitrypsin Deficiency: Coexistence in a Family with Progressive Liver Disease in the Proband

“…In this regard, it has been shown previously that the presence of hemochromatosis in family members of a proband is not linked solely to the presence of these specific HLA alleles, but is linked to the possession of a similar HLA haplotype as is present in the proband (3,20,21). In the present family, six members share the same HLA haplotype (A1, B8) as the proband (Figure 2) and might therefore be hemochromatosis heterozygotes.…”

Disorders of iron overload

“…67 Two main theories grew out of subsequent reports, namely that the primary disease was diabetes that then gave rise to cirrhosis and pigmentation or, alternatively, that the pigment was primarily derived from the blood. 70,71 The subsequent discovery that β 2 microglobulin knockout mice developed iron overload analo gous to human HC raised the postulate that the defective gene would be within an MHC molecule. 69 He described the entity as 'an inborn error of metabolism, which has an overwhelming incidence in males and which at times has a familial incidence' .…”