2602 delGをホモ接合体で有し小脳失調を呈した無セルロプラスミン血症の1例

A Case of Aceruloplasminemia Presenting as Cerebellar Ataxia with Homozygous Mutation nt2602 delG

　要旨　稀な常染色体劣性遺伝性疾患である無セルロプラスミン血症の1例を報告する。症例は58歳男性。若年時から糖尿病があり，数年前から小脳失調が出現した。血漿セルロプラスミンは感度以下でフェロキシダーゼ活性は0U/lであった。頭部MRIではT1, T2強調およびFLAIR画像にて両側尾状核，被殻，視床，小脳歯状核で低信号域がみられ，鉄の過剰沈着が示唆された。患者はExon15の1塩基欠損（2602delG）をホモ接合体で有し，父親はヘテロ接合体であった。中年期以降に失調症状や不随意運動を発症する糖尿病患者は本症を疑う必要がある。鉄過剰に伴い神経細胞障害をきたす点，加齢とともに神経症状が出現する点などで，神経変性疾患の発症機序を解明する上でも重要な疾患である。

　Aceruloplasminemia is an autosomal recessive disorder of iron metabolism caused by mutations in the ceruloplasmin（Cp）gene. We reported the results of clinical and molecular studies on a Japanese family with aceruloplasminemia. A 58-year-old man who had had diabetes mellitus for more than 30 years developed cerebellar ataxia several years before. He was found to have mild retinal degeneration too. Laboratory findings revealed a complete deficiency of serum ferroxidase activity and undetectable serum Cp. Magnetic resonance imaging showed a pronounced hypointensity in the bilateral putamina, caudate, thalamus and dentate nuclei on both T1- and T2-weighted images suggesting the presence of iron overload. We identified a homozygous deletion mutation（nt2602 delG）of the Cp gene in the patient, and the same heterozygous mutation in his unaffected father. To date, at least 29 mutations in the Cp gene have been identified. Although an individual with a heterozygous mutation has been believed to be an asymptomatic carrier like his father, some patients with such a condition were recently described to show neurological deficits. The variation in clinical findings may be explained partly by the difference in the severity of generation of free radicals caused by iron deposition or the environmental factors such as aging. Further investigations would be required to elucidate the molecular mechanisms of this late onset neurodegeneraion.

（Received : June 29, 2004）