Hereditary hemochromatosis

This page works the case through in full, answer included. If you would rather reason it out yourself: Play this case

How the diagnosis is reached

Five complaints that would each be unremarkable alone are one disease when they arrive together in a man of 48: fatigue, aching hands, diabetes, lost libido and a change in skin colour. The arthropathy is what should raise the question first, because it favours the second and third metacarpophalangeal joints, a distribution almost nothing else produces. The pigmentation is a slate-grey or bronze discolouration affecting sun-protected skin too, which distinguishes it from a suntan, and it results from both iron deposition and increased melanin. Diabetes arising in a man with a normal BMI reflects pancreatic islet iron deposition, and the hypogonadism is secondary, with inappropriately low gonadotrophins from pituitary iron loading: a normal caeruloplasmin argues against Wilson disease. The screening test is transferrin saturation, which rises before ferritin and is more specific; ferritin alone is an acute-phase reactant and can mislead. C282Y homozygosity confirms the diagnosis. The family history matters: his brother's liver disease and heart failure at a young age were almost certainly the same undiagnosed condition, and the inheritance is autosomal recessive. Treatment is therapeutic venesection, roughly 450 to 500 mL weekly and about 250 mg of iron per unit, until the ferritin falls below 50 µg/L, then maintenance every two to four months for life; deferasirox is held back for those who cannot tolerate it. The damage divides in two, which is what makes timing matter. Venesection reverses the pigmentation, fatigue and cardiac dysfunction and halts hepatic fibrosis, and at a liver stiffness of 9.1 kPa he has fibrosis rather than cirrhosis, so that half is still winnable. The diabetes and the arthropathy will not reverse whatever the ferritin does, which is the argument for screening his relatives before they reach this point.

Key clinical clues

• Arthropathy targeting the 2nd and 3rd MCP joints
• Slate-grey pigmentation including sun-protected skin
• Diabetes in a man with a normal BMI, plus secondary hypogonadism
• Transferrin saturation of 86%, which rises earlier and is more specific than ferritin
• Brother with liver disease and heart failure dying at 58: autosomal recessive inheritance

The case in full