Nerve high-resolution ultrasonography in tangier disease.

INTRODUCTION: Tangier disease (TD) is an autosomal recessive disorder characterized by severe reduction in high-density lipoprotein and accumulation of cholesterol esters in peripheral nerves and other tissues. The aim of this study was to evaluate whether nerve high-resolution ultrasonography (HRUS) can detect morphological nerve changes in TD. METHODS: Three related patients of a previously reported Italian family with Tangier disease, carrying the Y1698X mutation in ABCA1, underwent clinical, neurophysiological, and quantitative nerve HRUS evaluation. Nerve HRUS data were compared with normal controls. RESULTS: Despite neurophysiological abnormalities, no quantitative HRUS abnormality was detected in peripheral nerves. DISCUSSION: Normalcy of HRUS in neurophysiologically abnormal nerves suggests possible subtle abnormalities that escape quantitative HRUS detection. Systematic studies in larger TD cohorts with different mutations are needed to confirm our findings. Muscle Nerve 59:587-587, 2019.

[Valve Replacement for Severe Aortic Stenosis in a Patient with Tangier Disease].

We report a case of severe aortic valve stenosis in a patient with Tangier disease. A 64-year-old female was diagnosed with Tangier disease on the basis of gene mutation. The serum levels of total cholesterol and high-density lipoprotein were 124 mg/dl and 4.3 mg/dl, respectively. She had a symptom of dyspnea and echocardiography revealed severe aortic valve stenosis with the maximum gradient of 60.5 mmHg. Chest computed tomography showed severe calcification of the ascending aorta and the aortic root. Aortic valve replacement using a bioprosthetic valve was performed. Several reports have been made on coronary artery revascularization in Tangier disease patients, but one on surgical treatment for aortic valve stenosis is extremely rare.

Inherited disorders of HDL metabolism and atherosclerosis.

PURPOSE OF REVIEW: Genetic disorders of HDL metabolism are rare and, as a result, the assessment of atherosclerosis risk in individuals suffering from these disorders has been difficult. Ultrasound imaging of carotid arteries has provided a tool to assess the risk in hereditary hypo and hyperalphalipoproteinemia. This review gives a comprehensive summary. RECENT FINDINGS: Epidemiological studies have unequivocally shown that HDL cholesterol levels are inversely related to coronary artery disease risk, but the literature concerning genetic disorders of HDL metabolism provides less convincing information. Fortuitously, we were able to directly compare carotid intima media thickness data of substantial numbers of individuals with mutations in either apolipoprotein A-I (apoA-I), ATP binding cassette AI (ABCA1), lecithin: cholesterol acyltransferase (LCAT) or cholesteryl ester transfer protein. These data show that carriers of an apoA-I mutation exhibit the most pronounced accelerated atherosclerosis compared with those carrying mutations in ABCA1 and LCAT. Heterozygosity for a non-sense mutation in cholesteryl ester transfer protein did, by contrast, not distinguish carriers from controls in terms of intima media thickness progression. We will discuss these results in the context of the current literature. SUMMARY: Intima media thickness studies have provided evidence that hypoalphalipoproteinemia due to mutations in apoA-I, ABCA1, and LCAT is associated with increased progression of atherosclerosis. In contrast, hyperalphalipoproteinemia as a result of loss of cholesteryl ester transfer protein function is associated with unaltered atherosclerosis progression compared with family controls. This insight is of interest, since it can assist in the prioritizing of antiatherogenic therapy by increasing HDL cholesterol levels.

Increased carotid artery intima-media thickness in subjects with primary hypoalphalipoproteinemia.

The plasma concentration of high-density lipoprotein cholesterol (HDL-C) is inversely correlated with the incidence of atherosclerotic vascular events. In the present study, we evaluated pre-intrusive atherosclerosis in subjects with plasma HDL-C at the extremities of normal distribution. Fifty-five subjects with primary hypoalphalipoproteinemia (HypoALP) or hyperalphalipoproteinemia (HyperALP) were compared with fifty-five control subjects with average HDL-C levels, matched for sex, age, and plasma cholesterol. The average and maximal intima-media thicknesses (Avg-IMT and Max-IMT) of 48 carotid segments for each subject were approximately 40% greater in HypoALP than in control subjects (0.94 +/- 0.06 versus 0.69 +/- 0.04 mm, P=0.004, and 1.86 +/- 0.16 versus 1.35 +/- 0.10 mm, P=0.025, respectively). The IMT values in HyperALP subjects (Avg-IMT, 0.71 +/- 0.04 and Max-IMT, 1.38 +/- 0.14 mm) were the same as in controls. In a large cohort of hyperlipidemic subjects (n=559), significantly greater Avg-IMT and Max-IMT were found in subjects belonging to the first HDL-C quintile (<42 mg/dL) than in all the others. The measurement of carotid IMT in cases with HypoALP and HyperALP, and in a large series of hyperlipidemic patients, thus indicates that a low HDL-C is associated with significant pre-intrusive atherosclerosis, whereas a HDL-C level above average values does not lead to a further reduction of arterial wall thickening.

Characterization of atherosclerosis in a patient with familial high-density lipoprotein deficiency.

We describe the cardiovascular state of a 60-year-old homozygous patient with familial HDL deficiency (Tangier disease). The patient was examined by coronary angiography and intravascular ultrasound because of chest pain at rest and on exertion. We found a normal left ventricular function, moderately diffuse coronary sclerosis without stenosis and no critical stenosis of peripheral arteries. Intravascular ultrasound revealed the three layer appearance of arterial intima, media and adventitia with normal thickness. No calcified plaques or intimal hyperplasia could be detected apart from a single, discrete atherosclerotic lesion in one iliac artery segment. Concentric non-occlusive atherosclerotic lesions which are readily detectable with intravascular ultrasound were not found. The lack of severe atherosclerosis was remarkable insofar as massive foam cell formation and the virtually complete absence of circulating HDL is characteristic of Tangier disease and has been previously demonstrated in this patient. Our findings suggest that HDL deficiency and foam cell formation in Tangier disease are not necessarily associated with accelerated development of atherosclerosis.

Acute presentation of Tangier polyneuropathy: a clinical and morphological study.

We describe a patient with Tangier disease and a peripheral neuropathy with an unusual acute onset. The morphological studies of sural nerve biopsy revealed both axonal degeneration and demyelination, and the fiber loss was preferentially restricted to two of ten nerve fascicles. The cytoplasm of Schwann cells, fibroblasts, macrophages and pericytes were vacuolated because of the presence of numerous lipid droplets. The clinical and morphological findings are consistent with the possibility that ischemia plays a major role in causing this neuropathy.

Tangier disease: central nervous system impairment in a case of syringomyelia-like syndrome.

A neuroradiological investigation of the central nervous system (CNS) in a case of Tangier disease presenting as a syringomyelia-like syndrome is reported. No syringomyelinic cavities were found. However, MRI showed cervical spinal cord atrophy and scattered foci of greater density with T2 weighted images in the white matter of the frontal, parietal and occipital lobes. Cerebral and cervical spinal cord involvement in the course of Tangier disease is now shown for the first time. The authors postulate that the MRI detected alterations are related to the underlying illness.