Therapy with Chenodeoxycholic Acid

News

Yourlocation： Home > News > Therapy with Chenodeoxycholic Acid

CTX is a rare autosomal-recessive disorder of bile acidmetabolism due to a deficiency of mitochondrial sterol 27-hydroxylase, leading to a reduced production of Chenodeoxycholic Acid andsubsequently to an increased deposition of
cholesterol andcholestanol. CTX has therefore multisystem involvement and agreat variability in manifestation of all neurological and non-neurological symptoms.
Therapy with Chenodeoxycholic Acid. Here we report two siblings, with an extremely delayed diag-nosis of CTX, who had different clinical course and remainedundiagnosed till a significant disability. CTX is characterised by theassociation of tendon xanthomas, juvenile cataracts and multipleprogressive neurological symptoms, as progressive ataxia, pyra-midal signs, dementia, psychiatric disorders, seizures, peripheral neuropathy and dystonia. Other systemic manifestations mightinclude premature osteoporosis and atherosclerosis, respiratoryinsufficiency and heart involvement. Phenotype may vary from onepatient to another as it was for our two siblings. The diagnosis of CTX should be suspected in all cases characterized by combinationsof early cataract, mental retardation and spastic ataxia, particularlyon a background of tendon xanthomas. Brain MRI features includ ebilateral hyperintensity of the dentate nuclei and diffuse cerebraland cerebellar atrophy with white matter signal abnormalities. Laboratory test might show normal or low cholesterolemia.
In order to start a long-term replacement therapy with Chenodeoxycholic Acid, which may halt neurological symptoms. We report two Italian siblings having quite dif-ferent 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 cere-brotendinous xantomatosis in Italy and would like to suggest theimportance of genetic testing in patients with autosomal reces-sive spastic paraparesis associated with typical non-neurological symptoms.Molecular analysis in the CYP27A1 gene confirm the diagno-sis; most frequently mutations of CYP27A1 gene are distributedthroughout exons 1–8, and the majority are amino acid substitu-tions, although splice site mutations are also been described.We found a G-to-A transition at the 5-prime end in intron 7, caus-ing a splicing alteration with direct conjunction of exon 6 andexon 8 (c.1263 + 1A > G). This gene alteration has been previouslydescribed only once in a Japanese family; previous reportedcases of Cerebrotendinous xantomatosis were associated to morethan 50 mutations of the of the CYP27A1 gene.