Mark L. Bassett

Idiopathic hemochromatosis: demonstration of homozygous-heterozygous mating by HLA typing of families

SummaryIn five families with idiopathic (hereditary) hemochromatosis, clinical and biochemical expression of the disease occurred in offspring of probands, suggesting an autosomal dominant mode of inheritance. However, HLA typing of subjects indicated that a homozygous-heterozygous mating almost certainly had occurred in four of the five families, resulting in homozygous offspring. Thus, in these families inheritance of the hemochromatosis trait was best explained in terms of an autosomal recessive or intermediate mode of inheritance. This study demonstrates the value of HLA typing in identifying homozygous-heterozygous matings in hemochromatosis families.

Analysis of the cost of population screening for haemochromatosis using biochemical and genetic markers

AIMS To estimate the cost of population screening for haemochromatosis in Australia and to compare the cost of alternative screening strategies. METHODS The costs of screening for haemochromatosis were analysed in a hypothetical study using transferrin saturation as the primary screening test, with confirmation of the diagnosis by either liver biopsy or DNA testing for the recently-described haemochromatosis gene. RESULTS Screening, with confirmation of the diagnosis by liver biopsy, would cost between US

EARLY DETECTION OF IDIOPATHIC HÆMOCHROMATOSIS: RELATIVE VALUE OF SERUM-FERRITIN AND HLA TYPING

5079 and US

Idiopathic haemochromatosis in the Australian population: HLA linkage and recessivity.

8813 per case detected (excluding administrative costs), depending on the screening strategy (Aust

Is all genetic (hereditary) hemochromatosis HLA-associated

= US

Rehydration of air-dried smears. An alternative method for cytologic analysis of exfoliative cells.

0.80). If a DNA test were used instead of liver biopsy, the cost would be reduced to an estimated US

CASE REPORT: Antibiotic-associated haemorrhagic colitis

3954-US

Genetic hemochromatosis and HLA linkage

4410 per case. This would be further reduced to US

α1‐Antitrypsin phenotypes in chronic active hepatitis

2457 by detection of additional cases by screening family members. The least costly strategy utilised a transferrin saturation threshold of 55% and DNA testing for confirmation of the diagnosis; however, a transferrin saturation threshold of 45% increased the cost only marginally. The initial screening step (transferrin saturation) accounted for 74%-94% of the estimated cost of the screening programme. CONCLUSIONS Screening for haemochromatosis using transferrin saturation involves relatively modest costs which may be recovered if complications of haemochromatosis can be prevented by early detection and treatment. The most cost-effective strategies utilised transferrin saturation for initial screening, followed by DNA testing. Reduction in the cost of transferrin saturation would lead to a significant reduction in total screening costs. Additional benefits of a screening programme include detection of other iron overload disorders and iron deficiency.

Hepatocellular Carcinoma in Hemochromatosis

A study of 18 unrelated families with idiopathic haemochromatosis (I.H.C.) was undertaken to define the relative values of HLA typing and serum-ferritin estimation in the early detection of the disease. Sharing of both HLA haplotypes with the proband indicated a high risk of I.H.C. in siblings; but HLA typing was of limited value in detecting affected offspring. Non-identical HLA indicated a low risk of I.H.C. in both siblings and offspring. The presence of HLA A3 was not clinically useful as a marker for I.H.C., since this antigen was also present in 40% of unaffected relatives. In contrast, the serum-ferritin concentration was elevated in 96% of patients with I.H.C. and in only 5% of unaffected relatives. HLA typing provides some indication of the risk of I.H.C. in first-degree relatives, but the combination of serum-ferritin, serum-iron, and transferrin saturation remains the most reliable screening regimen for early diagnosis of I.H.C.