Peripheral neuropathy in Tangier disease: A literature review and assessment

Abstract

Tangier disease (TD) (OMIM#205400) is a rare cause of inherited metabolic neuropathies characterized by marked deficiency of high-density lipoproteins and accumulation of cholesterol esters in various tissue resulting from reverse cholesterol transport deficiency. We report a case of a patient with TD with multifocal demyelinating neuropathy with conduction block who presents with winging scapula, tongue, and asymmetric extremity weakness. We also present a review of all studies published from 1960 to 2017 regarding peripheral neuropathy in TD. Our search identified 54 patients with TD with peripheral neuropathy. Syringomyelia-like neuropathy subtype (52.4%) was more frequent than multifocal sensorial and motor neuropathy subtype (26.2%), focal neuropathy subtype (19.1%), and distal symmetric polyneuropathy subtype (2.4%). Splenomegaly was the most common (40.7%) clinical manifestation in these patients. The pattern of electrodiagnostic abnormalities are: (1) demyelinating abnormalities were more predominant in the upper extremities than in the lower extremities and (2) slowing of motor nerve conduction was more prominent in the intermediate segment than in distal nerve segments. The sural-sparing pattern was present in 34.6% and conduction block was present in 11.5% of the patients. Our literature review and our case showed the clinical spectrum of TD neuropathy is quite wide and that it should be considered in the differential diagnosis of non-uniform demyelinating neuropathies.

The Role of the ATP-Binding Cassette A1 (ABCA1) in Human Disease

“…TD is characterized by severe deficiency or absence of circulating HDL-C particles and accumulation of cholesteryl-esters in cells throughout the body, particularly in the reticuloendothelial system [7,8]. The major clinical signs of TD are very low HDL-C levels (<5 mg/dL), hyperplastic yellow orange tonsils and hepatosplenomegaly; while peripheral neuropathy occurs in approximately 50%, and premature coronary heart disease (CHD), occurs in 30 to 50% of TD patients [9][10][11]. Carriers of a single ABCA1 mutation (heterozygotes) have variable reductions in plasma HDL-C levels and a variable increased risk for CHD [12].…”

Lipid Transporters Beam Signals from Cell Membranes

“…Possessing the ability to translocate PS outwardly into the outer leaflet, ABCA1 has been linked to the phagocytosis of apoptotic cells [ 115 ]. Mutations in ABCA1 can cause Tangier’s disease, a genetic disorder marked by low HDL and ApoA1 levels causing an increased risk of atherosclerosis and peripheral neuropathy [ 116 , 117 ]. On the plasma membrane, ABCA1 regulates cholesterol redistribution from raft towards non-raft domains by promoting cholesterol efflux towards ApoA-1 ( Figure 2 C) [ 108 ].…”

Update on Neuropathies in Inborn Errors of Metabolism

“…One of the other rare IEMs presenting with such symptoms is Tangier disease, where focal and multifocal sensory and motor neuropathies account for, respectively, 26.2% and 19.1% of all neuropathies [18].…”

“…Multifocal sensory and motor neuropathy, accounting for approximately a quarter of all cases and focal neuropathy both demonstrate a relapsing-remitting pattern. Distal symmetric neuropathy, the rarest type, is either a stable or a progressive disease [18].…”