by Jackie Newman
Tangier Disease is an extremely rare autosomal recessive metabolic disorder.
Documentation shows that as of 1988, 27 cases of Tangier Disease had been
reported (Makrides pg.465) and in 1992 the reported cases were still fewer
than 50 persons worldwide (Thoene pg.265). The majority of the cases tend
to localize in one single area of the U.S., Tangier Island, Virginia. The
fact that most of the people that are affected by Tangier disease all live
in close proximity to one another could be due to Founder's effect. The
original settlers to the island came in 1686 and it is possible that one
or two of them were carriers of the disease or actually had the symptoms
and passed it down through the blood line.
Characteristics of Tangier Disease include increased levels or even a complete
absence of high-density lipoproteins (HDL) concentrations in one's plasma,
low cholesterol levels in the plasma, increased cholesteryl esters in the
tonsils, spleen, liver, skin and lymph nodes. One easily visual characteristic
usually found in children with Tangier disease is the presence of enlarged,
Initial research of Tangier disease showed a marked decrease in the HDL
concentrations when compared to normal controls. In some cases the reduction
was as great as 50% (Schmitz pg.6306). Scientists studied the HDL concentrations
and looked for any possible links in its involvement with the disease. They
specifically looked at the apo A-I (apolipoprotein) concentrations, which
is a major protein component of HDL.
The main hypothesis was that apo A-I was structurally abnormal. Studies
proved that this was incorrect because the DNA- derived protein sequence
for Tangier apo A-I was identical to the control groups apo A-I sequence
(Makrides pg.468). Scientists discovered that the cause of Tangier disease
is involved with the intracellular membrane trafficking of the HDL. Normally
macrophages inside the cell have receptors that bind the HDL. After the
HDL is bound it is transported into the endosomes. The endosome is transported
through the cell without any degradation by the lysosome and the HDL is
eventually resecreted from the cell. It is during this cycle that there
are problems for the Tangier disease people. When the HDL is allowed to
bind to the receptor monocyte, the two stick together but they never separate.
The HDL is not resecreted outside the cell (Schmitz pg.6308) The data suggest
that there is a deficiency in the cellular metabolism of HDL in the Tangier
monocytes. The HDL-monocyte unit together also supports the observed condition
of high concentrations of excess cholesterol in body tissues.
Currently the treatment for Tangier patients is dependent on the various
symptoms, ranging from heart surgery to removal of organs. Gene therapy
has been proposed as a possible treatment but is difficult because there
isn't anything wrong specifically with the gene involved in the HDL conversion.
The problem is in the cellular transportation. Many of the specific processes
within the cell are still not known so any extensive treatment is still
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