Treatment with chenodeoxycholic acid (CDCA) by Early diagnosis of CTXis

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Early and long-term treatment with chenodeoxycholic acid (CDCA) can slow down neurological symptoms progression, but diagnosis usually has a delay of several years. We report two Italian siblings having quite different phenotypes associated to a G-to-A transition in the c-1263 terminal causing a splicing alteration. This mutation has not been described before in Italy, and has been reported once in Japan. This case widens the clinical and genetic spectrum of Cerebrotendinous Xantomatosis in Italy and would like to suggest the importance of genetic testing in patients with autosomal recessive spastic paraparesis associated with typical non-neurological symptoms. Cerebrotendinous xanthomatosis (CTX) is an autosomal-recessive disorder of lipid storage caused by mutations in the CYP27A1 gene, coding for a sterol 27-hydroxylase, leading to increased deposition of cholesterol in multiple tissues. CTX is characterized by the association of early non-neurological manifestations and adult-onset neurological dysfunctions (spastic ataxia, dementia, psychiatric disorders, peripheral neuropathy). So it is very important to find CTX in early period.
Early diagnosis of CTXis important because early and long-term treatment with chenodeoxycholic acid (CDCA) could normalize cholestanol, improveneurophysiological signs, and potentially prevent clinical deteri-oration. Here we report a case of two siblings, with an extremely delayeddiagnosis of CTX, who had different clinical course but remainedundiagnosed till a significant disability. Genetic testing in healthysiblings revealed a status of heterozygous mutation carriers.
Detailed explanation as below: The proband and his affected sister have been treated withreplacement therapy with chenodeoxycholic acid (CDCA), without obtaining halt of disease progression. EEG showed generalized slowing of background activity. EMGshowed a sensory-motor polyneuropathy. Electrocardiogram and echocardiogram were normal. Abdomen ultrasound revealed gallbladder cholesterol polyps. Laboratory tests showed no abnor-malities including serum electrolytes, liver and kidney function,triglyceride and cholesterol levels. Ceruloplasmin and serum andurine copper were normal. Due to relentless progression of psychiatric and cogni-tive impairment, at the age of 36 years he has been hospitalizedin a nursing home. We performed brain MRI that revealed brain-stem and cerebellar atrophy, lesions in dentate nuclei, cerebral andcerebellar white matter, and hyperintensity of whole cortico-spinaltracts, all features consistent with a spinocerebellar ataxia.