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                 TANGIER DISEASE: A CASE REPORT
          G.K. Hovingh1, A. Van Tol2, A.H.M. Smelt3, M.R. Hayden4,
                    J.J.P. Kastelein1, J.A. Kuivenhoven1
1
    Department of Vascular Medicine, Academic Medical Center, Amsterdam,
2
    Department of Biochemistry, Erasmus University, Rotterdam, 3Department
        of Internal Medicine, Leiden University Medical Center, Leiden,
      The Netherlands, 4Center for Molecular Medicine and Therapeutics,
               University of British Columbia, Vancouver, Canada
Tangier Disease (TD) is a severe form of familial high-density lipoprotein
(HDL) cholesterol deficiency. This rare autosomal recessive disorder is
characterized by hepatosplenomegaly, peripheral neuropathy, enlarged
yellow tonsils and sigmoidal mucosa alterations. These clinical symptoms
are attributed to a typical accumulation of cholesteryl esters in macrophages
and reticuloendothelial cells. Recently, mutations in the gene encoding for
ATP-binding cassette A1 (ABCA1), a transmembrane protein pivotal for
cellular cholesterol efflux, were shown to be the underlying cause of this
disease. We here present a healthy HDL deficient, 48 years old man, who is
compound heterozygous for a missense mutation (resulting in an amino acid
substitution; T929I) and a de novo non-sense mutation (resulting in a
frameshift;GG5277,8C) in the ABCAI gene. Severely affected ABCA1
function was illustrated by a 70% reduction of cholesterol efflux from skin
fibroblasts as compared to control. Despite very low HDL-c (0.09mmol/L)
this man did not present with clinical stigmata of TD, nor with any sign of
vascular disease: EKG and B-mode ultrasonography of the carotids and
aorta revealed no abnormalities. In addition, the man did not present with
corneal opacities or hepatosplenomegaly. However, sigmoidoscopy revealed
an abnormal mucosa that (upon light microscopic examination) was
characterized by cholesterol laden mononuclear cells, characteristic for TD.
This extraordinary case illustrates that cholesterol efflux mediated by
ABCAI is not a prerequisite for protection against atherosclerosis.

				
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posted:9/2/2011
language:Afrikaans
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