File Download
Supplementary

Conference Paper: Cerebrotendinous xanthomatosis in seven Hong Kong Chinese

TitleCerebrotendinous xanthomatosis in seven Hong Kong Chinese
Authors
Issue Date2014
PublisherThe Endocrine Society.
Citation
The joint meeting of the International Society of Endocrinology and the Endocrine Society (ICE/ENDO 2014), Chicago, IL., 21-24 June 2014. How to Cite?
AbstractBACKGROUND: Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive disease characterized by the accumulation of cholestanol and cholesterol, leading to xanthomas and neurological symptoms. Genetic defect in CYP27A1 leads to a deficiency in sterol 27-hydroxylase and reduced chenodeoxycholic acid (CDCA) formation from cholesterol. The lack of negative feedback of CDCA on bile acid synthesis leads to increased production of cholestanol. Cholesterol production is also increased in CTX, but the role of statin therapy in these subjects is unclear. SUBJECT AND METHODS: The records of all adult Chinese CTX patients managed at our center were retrieved from our computerized record system. Clinical and biochemical parameters and drug history were reviewed. RESULTS: Seven adult CTX patients (5 males, 2 females) from 4 unrelated, non-consanguineous families were identified. The mean age was 31.0+/-9.4 years at first symptoms, 36.0+/-10.9 years at diagnosis and 48.9+/-7.0 years at the time of study. Reported first symptoms were xanthomata (n=5) and motor abnormalities (n=2). At presentation, all patients had bilateral Achilles tendon xanthomata, 4 patients had cerebellar sign and 3 patients had subnormal intelligence. Pre-treatment cholestanol level was 147.9+/-70.5 umol/l (reference range <13.0 umol/l), low-density cholesterol (LDL) level was 2.2+/-0.3 mmol/l, high-density cholesterol (HDL) level was 1.4+/-0.3 mmol/l and triglyceride (TG) level was 1.1+/-0.4 mmol/l. CDCA, at 750mg daily in 3 divided doses, was started at diagnosis in 4 patients and at 4 years post-diagnosis in 3 patients. After 1 year of treatment, mean cholestanol level was reduced to 13.0+/-11.6 umol/l (p<0.05), while no significant changes were noted in LDL (2.8+/-0.5 mmol/l), HDL (1.4+/-0.2 mmol/l) or TG (1.2+/-0.7 mmol/l). Simvastatin 10mg nocte in addition to CDCA in 3 of the 7 patients at 3.3+/-2.2 years after diagnosis did not lead to any change in cholestanol, LDL, HDL or TG levels at 5 and 10 years post-treatment commencement. Six patients had stable intelligence and were engaged in meaningful employment. No improvement in demyelinating changes in the brain on MRI was observed with treatment (assessed serially in 3 patients). Xanthoma regressed partially in 3 patients, was excised with no recurrence in 2 patients and remained stable in 2 patients. CONCLUSION: Our series is one of the largest of Chinese CTX patients, and possibly one of the longest longitudinally followed series of CTX patients, reported in the literature. Our data suggests that CDCA is effective in lowering cholestanol starting in the first year of treatment. Simvastatin at 10mg nocte seems to have no effect on circulating levels of cholestanol, LDL, HDL or TG at 5 and 10 years of follow-up. Further follow-up assessment may help to ascertain whether the reduction in cholestanol is associated with any clinical benefits.
DescriptionSession: SUN 0837-0868-Clinical Aspects of Lipid Metabolism and Disease Clinical
The Conference program's website is located at http://endowebcasting.com/endo/archives.htm
Persistent Identifierhttp://hdl.handle.net/10722/201285

 

DC FieldValueLanguage
dc.contributor.authorYuen, Men_US
dc.contributor.authorTam, SCFen_US
dc.contributor.authorFong, CHYen_US
dc.contributor.authorChow, WSen_US
dc.contributor.authorTan, KCBen_US
dc.contributor.authorLam, KSLen_US
dc.date.accessioned2014-08-21T07:20:20Z-
dc.date.available2014-08-21T07:20:20Z-
dc.date.issued2014en_US
dc.identifier.citationThe joint meeting of the International Society of Endocrinology and the Endocrine Society (ICE/ENDO 2014), Chicago, IL., 21-24 June 2014.en_US
dc.identifier.urihttp://hdl.handle.net/10722/201285-
dc.descriptionSession: SUN 0837-0868-Clinical Aspects of Lipid Metabolism and Disease Clinical-
dc.descriptionThe Conference program's website is located at http://endowebcasting.com/endo/archives.htm-
dc.description.abstractBACKGROUND: Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive disease characterized by the accumulation of cholestanol and cholesterol, leading to xanthomas and neurological symptoms. Genetic defect in CYP27A1 leads to a deficiency in sterol 27-hydroxylase and reduced chenodeoxycholic acid (CDCA) formation from cholesterol. The lack of negative feedback of CDCA on bile acid synthesis leads to increased production of cholestanol. Cholesterol production is also increased in CTX, but the role of statin therapy in these subjects is unclear. SUBJECT AND METHODS: The records of all adult Chinese CTX patients managed at our center were retrieved from our computerized record system. Clinical and biochemical parameters and drug history were reviewed. RESULTS: Seven adult CTX patients (5 males, 2 females) from 4 unrelated, non-consanguineous families were identified. The mean age was 31.0+/-9.4 years at first symptoms, 36.0+/-10.9 years at diagnosis and 48.9+/-7.0 years at the time of study. Reported first symptoms were xanthomata (n=5) and motor abnormalities (n=2). At presentation, all patients had bilateral Achilles tendon xanthomata, 4 patients had cerebellar sign and 3 patients had subnormal intelligence. Pre-treatment cholestanol level was 147.9+/-70.5 umol/l (reference range <13.0 umol/l), low-density cholesterol (LDL) level was 2.2+/-0.3 mmol/l, high-density cholesterol (HDL) level was 1.4+/-0.3 mmol/l and triglyceride (TG) level was 1.1+/-0.4 mmol/l. CDCA, at 750mg daily in 3 divided doses, was started at diagnosis in 4 patients and at 4 years post-diagnosis in 3 patients. After 1 year of treatment, mean cholestanol level was reduced to 13.0+/-11.6 umol/l (p<0.05), while no significant changes were noted in LDL (2.8+/-0.5 mmol/l), HDL (1.4+/-0.2 mmol/l) or TG (1.2+/-0.7 mmol/l). Simvastatin 10mg nocte in addition to CDCA in 3 of the 7 patients at 3.3+/-2.2 years after diagnosis did not lead to any change in cholestanol, LDL, HDL or TG levels at 5 and 10 years post-treatment commencement. Six patients had stable intelligence and were engaged in meaningful employment. No improvement in demyelinating changes in the brain on MRI was observed with treatment (assessed serially in 3 patients). Xanthoma regressed partially in 3 patients, was excised with no recurrence in 2 patients and remained stable in 2 patients. CONCLUSION: Our series is one of the largest of Chinese CTX patients, and possibly one of the longest longitudinally followed series of CTX patients, reported in the literature. Our data suggests that CDCA is effective in lowering cholestanol starting in the first year of treatment. Simvastatin at 10mg nocte seems to have no effect on circulating levels of cholestanol, LDL, HDL or TG at 5 and 10 years of follow-up. Further follow-up assessment may help to ascertain whether the reduction in cholestanol is associated with any clinical benefits.-
dc.languageengen_US
dc.publisherThe Endocrine Society.-
dc.relation.ispartofICE/ENDO 2014en_US
dc.titleCerebrotendinous xanthomatosis in seven Hong Kong Chineseen_US
dc.typeConference_Paperen_US
dc.identifier.emailTam, SCF: stam@hkucc.hku.hken_US
dc.identifier.emailFong, CHY: kalofong@hku.hken_US
dc.identifier.emailChow, WS: chowws01@hkucc.hku.hken_US
dc.identifier.emailTan, KCB: kcbtan@hku.hken_US
dc.identifier.emailLam, KSL: ksllam@hku.hk-
dc.identifier.authorityTan, KCB=rp00402en_US
dc.identifier.authorityLam, KSL=rp00343en_US
dc.description.naturelink_to_OA_fulltext-
dc.identifier.hkuros234433en_US
dc.publisher.placeUnited States-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats