Aceruloplasminaemia is a rare, autosomal recessive disorder of iron metabolism which results in iron deposition in the pancreas, brain, retina and liver. The clinical phenotype is distinctive: it typically leads to diabetes, anaemia and progressive neurodegeneration, but does not appear to cause functional retinal or hepatic impairment. We report an early case of aceruloplasminaemia in Australia and summarise the clinical sequelae and interesting aspects of their pathophysiology, especially that of diabetes.
A Sri Lankan male was diagnosed with aceruloplasminaemia in 1994 age 44 years, after presenting with type 2 diabetes mellitus in 1989 associated with mild microcytic anaemia and abnormal iron studies. Significantly, he had low serum iron 6.4 (14.0-32mmol/L) and serum copper 2.0 (12.5-18 µmol/L); normal transferrin 3.0 (2.0-3.6 g/L); and high ferritin 838 (40-20 µg/L). Liver biopsy showed an elevated iron content 9.91mg/g dry weight (0.40-1.30mg/g) with normal copper concentration 46 (15-70 µg/g), and no evidence of fibrosis. Empirical treatment with venesection resulted in profound anaemia suggesting a disorder of iron mobilisation. Ceruloplasmin was subsequently tested and found to be undetectable with a level of <0.05 (0.18-0.45g/L) confirming a diagnosis of aceruloplasminaemia. Since diagnosis, his clinical sequelae have comprised insulin dependent diabetes, anaemia and ultimately progressive neurodegeneration involving psychosis, depression, dementia and Parkinsonism. Treatment has involved iron chelation together with insulin, oral hypoglycaemics, antipsychotics, antidepressants and donepezil. The patient now requires assistance with all activities of daily living.
Aceruloplasminaemia was first described in 1987 and there are 56 case reports to date. Diabetes was developed by 85% of these patients and appears to be an early manifestation of this condition. The devastating neurodegenerative sequelae make early diagnosis and treatment essential. Screening should thus be considered when adult onset, antibody negative, insulin dependent diabetes is associated with anaemia and corroborative iron studies or unexplained neurodegenerative symptoms.