アミノ酸代謝異常による肝脳疾患特殊型の病態—Citrullinemiaを呈した3症例の臨床観察を中心に

THREE CASES OF JUVENILE HEPATO-CEREBRAL DEGENERATION WITH CITRULLINEMIA

I．はじめに

　最近，臨床的あるいは組織病理学的に肝脳疾患特殊型^4）と診断され，体液中Citrulline （Cit．）の増量を示した少数例の報告が，本邦において散見される^{5,8,10,11,15）}。これらには，乳幼児期からの反復する嘔吐，精神身体の発達遅滞など，その発端を生直後ないしは生後ごく早期に遡り得るもの^8,10,15）が合まれており，Citrullinemiaなどの先天性アミノ酸代謝異常症が肝脳疾患特殊型の一基礎疾患になり得ることが指摘されている^10,15）。類似の症例は外国にもみられるが^{9,12,20,21,23）}，一方で，生前Citrullinemiaが上証明され新生児期に急激に死の転帰をとる例のあることも報告されており¹⁹，²³），これらは，いわゆる肝脳疾患特殊型とその病態を異にしている。もちろん，Citrullinemiaが確認された症例の報告数がいまだに少ないために，臨床的，組織病理学的にも不明な部分が多く，肝脳疾患特殊型という包括的な概念との関連についても少なからぬ混乱が残されている。

　著者らも同様症例を経験しているが，主として，臨床経過の観察によつて得られた知見を中心に，症状形成過程に病因論的考察を加えて報告し，今後の資としたい。

　著者らも同様症例を経験しているが，主として，臨床経過の観察によつて得られた知見を中心に，症状形成過程に病因論的考察を加えて報告し，今後の資としたい。

It has been pointed out that some patients with juvenile Hepato-Cerebral Degeneration (Inose type) might bear congenital abnormalities in their amino-acid metabolism. However, knowledge about this point is still very little. In this report a patho-genic and pathoplastic discussion with regard to Hepato-Cerebral Degeneration with citrullinemia is presented.

The authors recently observed clinical courses in detail of three female patients with citrullinemia who had showed a tendency for peculiar unbalanced diets, mental and physical retardation and vomit-ting from their early life. They were admitted to the hospital after complaining of loss of cons-ciousness in varied degrees accompanied by nightcrying, irritability, excitation, hallucination, delu-sion or convulsion etc. at 9,18 and 22 years of age respectively. In all cases, livers were enlarged to 3 cm below the costal margin without any signi-ficant dysfunction. Liver biopsy of one case revealed fatty infiltration, cystes and hepatoma. Neuro-logically, hypotonia, hypertonia or spastic paresis of limbs were found. EEG revealed a generalised dysrhythmia often associated with high voltage slow waves or triphasic waves during unconscious-ness. The cupper metabolism was normal and Keyser-Fleisher's ring was not observed. The sequence of unconsciousness and coma suggested an impairment of ammonia metabolism. This was confirmed by the high level of plasma ammonia. Also the level of plasma citrulline (104-327 umole/l) was higher than control (17-41), and the activity of arginosuccinic acid synthetase (18 umole/60 min./ g wet liver) in one case was lower (43-84). Two cases are (20 and 24 years of age) under low protein diets, but one case died at 31 (necropsy was not performed).

It is supposed that the mental and physical re-tardation from infancy in these cases is attributable to the congenital derangement in urea cycle and the disorder of consciousness later manifested re-sulted from the toxic effect of ammonia. Citrulline-mia strictly departs from the present conception of Hepato-Cerebral Degeneration. However, it is con-ceivable that some patients with citrullinemia may closely resemble Hepato-Cerebral Degeneration in clinical manifestations just as the cases presented.