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Hereditary haemochromatosis — ESEGH MCQ

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HardHepatologyHereditary haemochromatosisESEGH

A 54-year-old White British man of northern European ancestry is investigated for mildly abnormal liver blood tests. He has diabetes mellitus, second- and third-metacarpophalangeal joint arthralgia, and a brother who died from unexplained cirrhosis. He has no history of regular red-cell transfusion and his C-reactive protein is normal. Repeat morning testing shows a ferritin concentration of 1240 micrograms/L and transferrin saturation of 68%. Ultrasound demonstrates a nodular liver without a focal lesion. Which investigation is the most appropriate next test to establish the aetiological diagnosis?

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Correct answer: A — HFE p.C282Y genotyping

The correct answer is A. In a man of European ancestry, transferrin saturation above 50% with ferritin above 300 micrograms/L should prompt HFE p.C282Y genotyping; p.C282Y homozygosity together with this biochemical phenotype establishes HFE haemochromatosis. Diabetes, metacarpophalangeal arthropathy and familial cirrhosis further increase the pre-test probability. MRI liver iron quantification is particularly important if p.C282Y homozygosity is absent or the cause of iron overload remains uncertain. Transient elastography is also required to assess fibrosis but does not establish the aetiology. Liver biopsy is not a first-line diagnostic test for HFE haemochromatosis, although it may be considered for unresolved fibrosis staging when ferritin exceeds 1000 micrograms/L. An extended non-HFE gene panel follows specialist assessment when HFE testing is non-diagnostic and hepatic iron overload is demonstrated.

Reference: European Association for the Study of the Liver. EASL Clinical Practice Guidelines on haemochromatosis, diagnostic approach and genetic testing recommendations, 2022. https://easl.eu/wp-content/uploads/2022/06/PIIS01688278220021121.pdf