Abstract
We studied the long-term effect of CDCA and a competitive HMG-CoA reductase inhibitor (CS-514) on clinical symptoms and sterol metabolism in three patients from one family with CTX. Proband (case 1, 36 y.o., male) manifested marked tendon xanthomas and mild dementia with obvious encephalographic abnormalities. He was treated for two years with CDCA (0.8g/day) and further for one year with combination of CS-514 (10mg/day) and CDCA (0.8g/day). His two siblings (case 2 and 3, 31 and 29 y.o., females) showed tendon xanthomas and cerebellar ataxia or pyramidal sign complicated with hyperthyroidism. They were given CDCA (0.4g/day) for a year and further for one year CS-514 singly.
Plasma cholestanol levels before treatment were approximately 3mg/dl in all cases which were twenty times of controls. In proband, plasma cholestanol was reduced from 3.12mg/dl to 1.96mg/dl by CDCA and further to 0.92mg/dl by combination therapy with CS-514. Whereas plasma cholesterol was slightly increased by CDCA and reduced by combination therapy. Administration of CDCA also resulted in substantial reduction of plasma cholestanol in his siblings but single treatment with CS-514 caused no reduction of plasma cholestanol. These findings suggest that plasma cholestanol lowered by the increase of bile acid pool supplemented with CDCA, which may enhance feed back mechanism of 7α-hydroxylase, and still more decreased by combination with the inhibition of sterol synthesis.
Clinically, in case 1, his xanthomas regressed remarkably and the mental detardation improved associated with normalization of electroencephalographic abnormalities after treatment with CDCA and combination with CS-514. In his sisters, tendon xanthomas also regressed and neurologic symptoms improved after treatment with CDCA.
We conclude that combination therapy with CDCA and CS-514 is effective for the correction of biochemical abnormalities much more than with single treatment of CDCA.
