Lysosomal lipid vacuoles in macrophages located in the colon

Excerpt

A 22-year old female patient presented with abdominal pain, diarrhea, and a history of tonsillectomy. Ultrasound showed an enlarged spleen with a diameter of 13 cm. There was no hepatomegaly or peripheral neuropathy. Lab results were remarkable for a low high-density lipoprotein (HDL) cholesterol level (3 mg/dl, normal ≥40 mg/dl). A sigmoidoscopy showed yellowish lesions. Light microscopy showed foam-cell disposition in the submucosal layers. Electron microscopy revealed lysosomal lipid vacuoles and crystalline cholesterol clefts in the cytoplasm of macrophages (see Fig. 1). Other sites of foam-cell deposition were found in biopsies from the gastric mucosa. Apolipoprotein A1 (apo-A1) level was <0.1 g/l (normal 1.08–2.25 g/l). A homozygous mutation C342T near exon 22 was found, resulting in a stop codon at the glutamine level in position 1038. This leads to a deficiency in ABCA1, an adenosine triphosphate (ATP)-binding cassette transporter, which suggests a diagnosis of Tangier’s disease. Under normal circumstances, this plasma membrane protein has been shown to mediate cholesterol efflux to nascent, apo-A1-rich HDL particles (Brewer et al. 2004). The lack of cholesterol efflux by the deficient ABCA 1 to nascent HDL increases catabolism of this lipid-poor HDL particle (Remaley et al. 1997). The characteristic clinical findings include the presence of enlarged yellow tonsils, splenomegaly, and peripheral neuropathy. Other sites of foam-cell deposition include bone marrow and rectum. In view of a low HDL cholesterol, Tangier’s disease is one disease that needs to be suspected (Breslow 2000). Other causes of low HDL cholesterol are lecithin-cholesterol acyltransferase (LCAT) deficiency, familial HDL deficiency, and some of the sphingolipidoses. Tangier’s disease can manifest in the gastrointestinal tract. There is need for search for this disease because patients are at risk for atherosclerotic complications. They can benefit from lipid-lowering drugs and general lifestyle modifications.

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