Diagnosis, treatment, and clinical outcomes in 43 cases with cerebrotendinous xanthomatosis.

Background Cerebrotendinous xanthomatosis (CTX) is a rare disorder due to defective sterol 27-hydroxylase causing a lack of chenodeoxycholic acid (CDCA) production and high plasma cholestanol levels. Objectives Our objective was to review the diagnosis and treatment results in 43 CTX cases. Methods...

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Publicado en:Journal of Clinical Lipidology Vol. 12; no. 5; pp. 1169 - 1179
Autores principales: Duell, P. Barton, Salen, Gerald, Eichler, Florian S., DeBarber, Andrea E., Connor, Sonja L., Casaday, Lise, Jayadev, Suman, Kisanuki, Yasushi, Lekprasert, Patamaporn, Malloy, Mary J., Ramdhani, Ritesh A., Ziajka, Paul E., Quinn, Joseph F., Su, Kimmy G., Geller, Andrew S., Diffenderfer, Margaret R., Schaefer, Ernst J.
Formato: research tables/charts Journal Article
Publicado: Elsevier B.V. Sep2018
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Sep2018
      vid: 12
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      pub: Elsevier B.V.
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        10.1016/j.jacl.2018.06.008
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        atl: Diagnosis, treatment, and clinical outcomes in 43 cases with cerebrotendinous xanthomatosis.
      aug:
        au:
          Duell, P. Barton
          Salen, Gerald
          Eichler, Florian S.
          DeBarber, Andrea E.
          Connor, Sonja L.
          Casaday, Lise
          Jayadev, Suman
          Kisanuki, Yasushi
          Lekprasert, Patamaporn
          Malloy, Mary J.
          Ramdhani, Ritesh A.
          Ziajka, Paul E.
          Quinn, Joseph F.
          Su, Kimmy G.
          Geller, Andrew S.
          Diffenderfer, Margaret R.
          Schaefer, Ernst J.
        affil: Knight Cardiovascular Institute, Oregon Health and Science University, Portland, OR, USA
      sug:
        subj:
          Lipid Metabolism, Inborn Errors Diagnosis
          Lipid Metabolism, Inborn Errors Drug Therapy
          Human
          Treatment Outcomes
          Adult
          Diarrhea
          Chronic Disease
          Cognition Disorders
          Cataract
          Tendons Pathology
          Nervous System Diseases
          Cardiovascular Diseases
          Cholesterol Blood
          Steroids Blood
          Bile Acids and Salts Therapeutic Use
          Bile Acids and Salts Administration and Dosage
          Administration, Oral
          Adult: 19-44 years
      ab: Background Cerebrotendinous xanthomatosis (CTX) is a rare disorder due to defective sterol 27-hydroxylase causing a lack of chenodeoxycholic acid (CDCA) production and high plasma cholestanol levels. Objectives Our objective was to review the diagnosis and treatment results in 43 CTX cases. Methods We conducted a careful review of the diagnosis, laboratory values, treatment, and clinical course in 43 CTX cases. Results The mean age at diagnosis was 32 years; the average follow-up was 8 years. Cases had the following conditions: 53% chronic diarrhea, 74% cognitive impairment, 70% premature cataracts, 77% tendon xanthomas, 81% neurologic disease, and 7% premature cardiovascular disease. The mean serum cholesterol concentration was 190 mg/dL; the mean plasma cholestanol level was 32 mg/L (normal <5.0 mg/L), which decreased to 6.0 mg/L (−81%) with CDCA therapy generally given as 250 mg orally 3 times daily. Of those tested on treatment, 63% achieved cholestanol levels of <5.0 mg/L; 91% had normal liver enzyme levels; none had significant liver problems after dose adjustment. Treatment improved symptoms in 57% at follow-up, but 20% with advanced disease continued to deteriorate. In the United States, CDCA has been approved for gallstone dissolution, but not for CTX despite long-term efficacy and safety data. Conclusions Health care providers seeing young patients with tendon xanthomas and relatively normal cholesterol levels, especially those with cataracts and learning problems, should consider the diagnosis of CTX so they can receive treatment. CDCA should receive regulatory approval to facilitate therapy for the prevention of the complications of the disease. Highlights • CTX should be considered in patients with premature cataracts and/or xanthomas. • The diagnosis of CTX is made by finding plasma cholestanol levels >10.0 mg/L. • Familial hypercholesterolemia and sitosterolemia can cause high cholestanol levels. • The diagnosis of CTX can be confirmed by CYP27A1 gene analysis. • The complications of CTX can be prevented by treatment with chenodeoxycholate.
      pubtype: Academic Journal
      doctype:
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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