Fabry病—典型例と部分酵素欠損例からの自律神経機能異常の考察

Fabry's disease; analysis of autonomic dysfunction in a patient with partially deficient hydrolysis of ceramide trihexoside and five typical cases.

I．はじめに

　Fabry病はリソソーム水解酵素の一つであるα-galactosidase Aの遺伝的欠損による中性糖脂質蓄積症であり，伴性劣性遺伝形式をとる^5,13）。臨床的には学童期より疼痛発作，発汗低下，被角血管腫，角膜混濁を呈し，後に腎障害，心血管病変，脳血管障害を併発して，多くは30歳から40歳代で死亡する^5,34）。

　1987年，Tsujiらにより本酵素のcDNAの全塩基配列が決定され，本酵素遺伝子はX染色体長腕上（Xq 13.1-Xq^22）に位置していることが明らかにされた^32）。蓄積物質は，ceramide trihexoside（CTH），ceramide dihexoside（CDH）およびB型血液型物質などの非還元末端にα位で，ガラクトースが結合したスフィンゴリピドである^5）。糖脂質の蓄積は全身諸組織で認められ，とくに血管壁において高度である^5,24,30）。神経系における糖脂質蓄積には明瞭な選択性がみられ，末梢および中枢自律神経ニューロンに著しい^24,30）。

　We evaluated functions of the autonomic nervous system in 6 males with Fabry's disease. Five had typical clinical features of Fabry's disease with complete deficiency of α-galactosidase A, while an atypical case (case 1) with partial deficiency of the enzyme in the cultured fibroblasts had severe pain in the extremities but had no angiokeratoma, corneal clouding, and hypohidrosis.

　Following results were observed in the autonomic function tests in the case 1; (1) reduction of R-R interval variation, abnormal Valsalva ratio (hyporeactivity in cardioaccelerator response during Valsalva strain), hyperreactivity in pilocarpine test and no reactivity in atropine test, suggesting abnormalities of the parasympathetic nervous system, (2) hyperreactivity to epinephrine test and norepinephrine infusion test, normal reactivity to isoproterenol infusion test and diminished response of plasma norepinephrine on standing, suggesting the denervation of peripheral α-adrenergic fibers, and (3) completely normal sweating induced by heating, acetylcholine injection or pilocarpine injection and normal Galvanic skin response (GSR) on the palm.