GENE ANALYSIS AND LIPID PEROXIDATION ASSOCIATED WITH INCREASED IRON IN PATIENTS WITH ACERULOPLASMINEMIA

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Aceruloplasminemia is a newly recognized autosomal recessive disorder of iron metabolism resulting in neurodegeneration of the retina and basal ganglia as well as diabetes mellitus. Clinically it is recognized as a triad of diabetes, retinal degeneration and neurologic disease. This disease is characterized by mutations in the ceruloplasmin gene, the absence of serum ceruloplasmin, low serum iron concentration, and iron accumulation in the brain, liver, and other tissues.1) Iron in an important catalyst of oxyradical-mediated cellular and tissue injury. CSF from affected patients revealed a three-fold increased iron concentration which was associated with increased superoxide dismutase activity and lipid peroxidation products. These findings support the hypothesis that iron-mediated lipid peroxidation contributes to neurodegeneration in patients with aceruloplasminemia. Such measurements may have value in assessing disease progression as well as the results of iron chelation and other therapeutic interventions.2) We screened the serum ceruloplasmin concentrations of 4,990 healthy adult individuals. Subsequent sequence determination of the mutant alleles showed three mutations (one homozygote and five heterozygotes). The gene frequency was 70x/100,000. In Japan, the incidence of aceruloplasminemia was estimated to be approximately one per 2,000,000 in the case of non consanguineous marriages.3) We report a 70-year-old woman with parkinsonism and late onset diabetes mellitus who had a novel mutation in the ceruloplasmin gene. Nucleotide sequence analysis of the ceruloplasmin gene showed a single bp deletion (G : nt 2068) in exon 11. This mutation produced a frame shift, resulting in the premature termination at aa 690.