Accelerated Atherogenicity in Tangier Disease

Abstract

We report a case of Tangier disease with Leriche syndrome and bleeding tendency. In this male patient, nasal hemorrhage had been observed frequently throughout childhood. At 46 years old, he experienced effort angina, and coronary angiography demonstrated 75% stenosis in the right coronary artery. Orange-colored tonsils, mild hepatosplenomegaly and very low levels of serum high-density lipoprotein cholesterol (HDL-C) were observed, and the patient was diagnosed with Tangier disease. At 52 years old, effort angina recurred. Coronary angiography revealed 75% stenosis of the left main trunk, left anterior descending, and right coronary arteries. Stenosis of the brachiocephalic and right common iliac arteries was also recorded. Stents were implanted, and coronary artery bypass surgery was performed. At 53 years old, 15 months after surgery, the patient reported intermittent claudication, coldness of feet, and impotence. Aortic angiography showed progression of the stenosis at the bifurcation of the common iliac artery. The patient was diagnosed with Leriche syndrome, and aorta-left external iliac artery graft bypass surgery was performed. After surgery, oozing from subcutaneous tissue and leaking from the anastomotic region were observed. Additional analysis revealed two single-nucleotide polymorphisms (V825I and N935T) in the ATP-binding cassette transporter A1 (ABCA1) gene, and accumulation of small dense low-density lipoprotein together with low levels of HDL-C. In Tangier disease, HDL-C is markedly decreased because of ABCA1 deficiency. However, this is the first reported case to exhibit extensive atherosclerosis and bleeding tendency. This patient had atypical extensive and multiple atherosclerotic lesions, accompanied by Leriche syndrome and uncontrollable bleeding.

Keywords: ABCA1; Atherosclerosis; HDL; Leriche syndrome; Tangier disease.

Fig. 1.

Coronary and aortic angiography before and after coronary artery bypass graft surgery at the age of 52 In the left coronary artery (LCA), 75% stenosis was observed in the left main trunk ostium (A). In the right coronary artery ostium (RCA), moderate to severe diffuse stenosis was observed (B). In addition, multiple severe calcified lesion were observed in both the LCA and RCA on coronary angiography. Angiography of the aortic arch revealed irregular and eccentric stenosis of the brachiocephalic artery (C). This lesion was treated with stent implantation (8 × 27 mm) (D). A huge lesion was observed in the left subclavian artery (E). Angiography of the abdominal aorta and lower limbs showed severe stenosis in the right common iliac artery (open arrow) (F, G), whereas the right internal iliac artery was not contrasted (open arrowhead). In addition, severe stenosis was found in the left internal iliac artery (closed arrowhead). Angiography of the right lower limb revealed stenosis with dissection in the right common iliac artery (H). This lesion was treated with stent implantation (10×60 mm) (I). Abdominal aortic angiography, 2 years after coronary artery bypass graft surgery, when the patient was 53 years old. During angiography of the aortic arch, newly developed multiple severe stenoses were observed at the bifurcation of the common iliac artery. The arrowhead indicates the dissection of the abdominal aorta, which had not been observed 2 years previously (Fig. 1-F)) (J). Three-dimensional CT angiography of the coronal section showed severe stenosis with calcification at the ostium of the left renal artery and near the bifurcation of the common iliac artery (K). Three-dimensional CT angiography in the sagittal view showed multiple severe irregular stenoses of the abdominal aorta (open arrow) and dissection of the celiac artery (open arrowhead) (L).

Fig. 2.

Photos of tonsils of the proband. The lingual tonsil (A) and pharyngeal tonsil (B) were orange-colored and swelling, which is a typical characteristic in Tangier disease

Fig. 3.

Peripheral blood was stained by Giemsa (×1000). Both normal platelets (closed arrow) as well as abnormal giant ones (closed arrowhead) were observed. In addition, erythrocytes with numerous stomatocytes (arrowhead) were observed (A). Lipoprotein agarose gel electrophoresis was carried out. In this case, HDL was not observed at the arrow (B). The peak of VLDL (*) was high, and a mid-band was observed between VLDL (*) and LDL, suggesting accumulation of remnant. In this case, the second peak (arrow) was moved to the right, indicating accumulation of small-sized LDL (C). A putative model of ABCA1 mutation, V825I and N935T (D).