家族例におけるWilson病の臨床と生化学

Clinical and Biochemical Aspects in Wilson's Disease among Several Families

I．緒言

　Wilson病は最近診断技術の進歩により症例が増加したとはいえ，元来稀な疾患に属し，しばしば家族性に発病することが知られているにもかかわらず，同胞例，特に3名以上の発現をみた家系の詳細な報告は意外に乏しい^1）〜4）。従つて家族例を対象とした研究も文献上ほとんどみられず，Bearn^5），Sullivan^2）らにより若干の知見が報告されている程度である。この事実は本症の遺伝学的研究上のひとつの大きな難点であり，臨床病理学的に重要な問題が残されていると思われる。

　東北大学神経精神科では1954年に萱場^6）がWilson病の剖検例を報告して以来かなりの症例に接してきた^7）〜9）。著者は最近病理学的にも確認された典型的Wilson病3例と無症状性Wilson病1例の4同胞例を臨床病理学的に詳細に検討して，興味ある知見を発表した^10）。本論文では別な4家系の症例を加えて，特に家系例を中心として臨床面，生化学面にさらに検討を加え，本症の遺伝様式を考察してみた。

Five families with fourteen patients with Wilson's disease were studied clinically and biochemically, and the genetic mode was discussed. The ages of onset in siblings were almost the same with little difference except two sisters.The durations of the disease were extremely coincident in siblings without exceptions. Some clinical symptoms com-mon to three sisters of the first family, such as personality disorder as an initial symptom and extrapyrainidal signs and Kayser-Fleischer rings were observed. In addition, sisters showed almost complete similarity in the onset and course of the extrapyramidal signs and autonomic disturbances were supposed to be present commonly to siblings of the second and the third families. Especially, tremor appeared in the early time of the disease and obvious renal disturbance was present com-monly to siblings of the second family. The clinical course was characteristically slow, but the symp-toms were severe except the difficulty in swallow-ing, in sisters of the fourth family. Consequently the detailed analysis of clinical features enables us to emphasize the fairly close similarity that siblings bear in the onset and course of chief and atypical symptoms.

Investigations of the reports by other authors were discussed and proved to support the result of this research.

As for the copper metabolism, serum copper oxidase activity (caeruloplasmin) and total serum copper level were both strikingly decreased in the patients and there was an evident difference in copper metabolism between patients and their normal relatives including parents. The ratio of serum direct-reacting copper and total copper levels was increased to more than 45% and also 24-hour urinary copper output was enormously increased in patients. By the biochemical investigation of the healthy relatives, a case of asymptomatic Wil-son's disease was found, but no characteristic finding was found in heterozygous carrier in that manner.

The author has found almost the same clinicopa-thological findings in sister cases of the first family. From these observations, a uniform process of the disease may be considered in the siblings with Wilson's disease. Subsequently the basic distur-bance of the disease may be caused by a single factor, not by multiple factors, for example, three complicated factors. It may safely be asserted that the genetic mode of the disease is au autosomal single recessive one.