An unusual case of iron overload

A 36-year-old Pakistani male presented to the gastroenterology department of a Queensland hospital for investigation of an elevated serum ferritin (1132 μg/L) and mild derangement of his liver enzyme (ALT 64 U/L). Pertinent points in the history included, no family history of liver disease, no ethanol consumption, no IV-drug use or tattoos, normal BMI, consanguineous parents (1st cousins) and no regular medication. His examination was unremarkable except for some mild right upper quadrant tenderness. A full liver screen was initiated with results being remarkable for an undetectable ceruloplasmin, a normal 24-hour copper excretion, elevation of serum ferritin (900 μg/L) with a low serum iron (4 μmol/L) and transferrin saturation (6%). Also of note was a mild anaemia (Hgb 117 g/L) and mild decrease in mean cell haemoglobin. Aceruloplasminaemia was confirmed by ferroxidase activity assay and genetic testing revealing the patient to be homozygous for the ceruloplasmin G650R mutation, leading to disruption of the copper binding capacity of ceruloplasmin and complete hepatic ceruloplasmin degradation. Iron loading of the liver and brain was confirmed by MRI. This case highlights the importance of ceruloplasmin in iron homeostasis, with aceruloplasminaemia leading to a lack of iron mobilisation from hepatic and brain parenchyma leading to atypical iron overload and neurodegeneration.