Identification of homozygous hemochromatosis subjects by measurement of hepatic iron index

Abstract

The value of measurement of hepatic iron concentration and determination of the hepatic iron index in distinguishing homozygotes from heterozygotes for hemochromatosis was examined. The study group included 42 homozygotes with an unequivocal diagnosis of hemochromatosis and six individuals who had initial equivocal results but were established as homozygous after extensive follow-up. These were compared with 15 heterozygotes with no sign of increasing body iron stores who had undergone liver biopsy because of an initial suspicion of raised iron levels. In these subjects a hepatic iron concentration of greater than 75 mumol/gm dry weight was clearly indicative of homozygous hemochromatosis. Body iron accumulation was age-related both in homozygotes and in these heterozygotes with mild biochemical abnormalities (r = 0.476; p = 0.001 and r = 0.689; p = 0.01, respectively), with a rate of accretion of approximately 5 mumol/gm dry weight/year in homozygotes and 0.9 mumol/gm dry weight/year in heterozygotes. Thus, lower values in young subjects may be consistent with homozygosity, and higher values in older individuals are consistent with heterozygosity. To overcome this problem, the hepatic iron index (hepatic iron concentration divided by age in years) was analyzed and found to separate the two groups effectively, with no homozygote having an index of less than 1.9 and no heterozygote having an index of greater than 1.5. These results in a series of patients who have been followed for a median of 3 yr (range = 1 to 30 yr) validate the use of the hepatic iron index to discriminate hemochromatosis homozygotes from heterozygotes with raised levels of serum ferritin, transferrin saturation or both.

Clinique, diagnostic et traitement de l'hémochromatose héréditaire

“…-tests hépatiques anormaux [13]. L'HII se calcule par le quotient de la concentration intrahépatique de fer (µmol/g de poids sec) et l'âge du patient en années; un cut-off de 1,9 ou 2,0 permet de distinguer de façon fiable un homo-d'un hétéro-zygote [13].…”

“…L'HII se calcule par le quotient de la concentration intrahépatique de fer (µmol/g de poids sec) et l'âge du patient en années; un cut-off de 1,9 ou 2,0 permet de distinguer de façon fiable un homo-d'un hétéro-zygote [13]. Pour l'HII, il faut envoyer au laboratoire une biopsie native de 0,5-1,0 cm de long, sans liquide.…”

the screening, diagnosis and optimal management of haemochromatosis

“…44 At present, liver biopsy with a histological assessment of the degree and distribution of iron stores, together with a biochemical quanti®cation of the hepatic iron stores, is the gold standard in diagnosing an index case of haemochromatosis. 45,46 The subsequent diagnosis of iron overload in an HLA-identical sibling clinches the diagnosis. Liver biopsy is also the only reliable way to determine the presence or absence of cirrhosis, the most important prognostic factor in haemochromatosis.…”

“…A hepatic iron index >2 has been shown to be reliable in differentiating homozygous haemochromatosis from heterozygous haemochromatosis, alcoholic liver disease and chronic liver disease in general. 45,46 However, this is currently being reassessed in light of the more precise diagnosis by the C282Y mutation. Up to 30% of patients with symptomatic haemochromatosis have been found to consume more than 50 g alcohol/day.…”

Hepatic Iron Overload: Direct HLA-HMutation AnalysisvsQuantitative Iron Assays for the Diagnosis of Hereditary Hemochromatosis

“…12,13 The nonspecificity of these serum iron markers has led to quantitative determinations of hepatic iron levels for the accurate diagnosis of HH. Although a hepatic iron index (HE; an age-adjusted hepatic iron concentration) above 1.9 has been used as the "gold standard" for distinguishing HH from other less treatable iron overload disorders (particularly alcoholic siderosis), [14][15][16] the specificity of this test may be poor in patients with hepatitis C-or alcohol-induced cirrhosis.…”