Stepwise Facial and Upper Limb Weakness and Small Fiber Sensory Loss—Tangier Disease

Figure 25-1 Electron micrograph of a radial sensory nerve with numerous macrophages and Schwann cells containing non–membrane-bound lipid vacuoles (arrows).


Tangier disease is a condition characterized by severe deficiency of HDL cholesterol. The disease is named after the location where the first two siblings with the condition were described, on Tangier Island, Virginia, in the Chesapeake Bay. It is an autosomal recessive disorder, with fewer than 60 cases reported worldwide.1 Clinical features include male predominance (2:1), orange tonsils, organomegaly, thrombocytopenia, corneal opacities, atherosclerosis, and peripheral neuropathy. Neuropathy occurs in approximately two thirds of patients and is the initial symptom in one half of patients.

There are three forms of peripheral neuropathy: (1) Multiple mononeuropathies, typically involving cranial, long thoracic, and limb nerves, with fluctuating weakness and sensory loss punctuated by exacerbations and remissions (this pattern tends to occur in adolescents and young adults); (2) a generalized, slowly progressive, symmetric, sensorimotor, length-dependent polyneuropathy; and (3) a syringomyelia-like form, with slowly progressive facial diplegia, variable wasting and weakness of hand and arm muscles, and loss of pain and temperature sensation over the hands, arms and trunk, sparing the legs.14 This form occurs in adults and has a slowly progressive course. Neuropathic (Charcot’s) arthropathy of the shoulder joint is an unusual feature in this case and has not been reported as a complication of Tangier disease.

The diagnosis is established with a lipid profile demonstrating absent or severely deficient HDL levels; the associated findings of decreased total cholesterol and elevated triglyceride levels are characteristic for homozygote carriers.

Electrodiagnostic findings vary based upon the clinical pattern. In those with multiple mononeuropathies, there is a multifocal axon loss pattern with reduced or absent sensory nerve action potentials (SNAPs) and low compound muscle action potentials of affected nerves. In the syringomyelia-like form, changes are limited to the upper limbs. There are reduced or absent SNAPs, low motor amplitudes, prolonged distal motor latencies and late responses, and slowed conduction velocities consistent with a demyelinating or mixed axonal and demyelinating pattern.1

Nerve biopsy in the syringomyelia-like form shows loss of small myelinated and unmyelinated fibers and dorsal root ganglion cells with lipid accumulation within Schwann cells.5 The lipid is within non–membrane-bound vacuoles and also may be present in endoneurial fibroblasts and macrophages. Demyelination and remyelination without axonal degeneration also may be observed.3

The pathogenesis of Tangier disease is due to a mutation of the ATP binding cassette transporter 1 (ABC1) gene on chromosome 9q31. The gene codes for the ABC1 protein located on the cell surface and transports cholesterol from cells to plasma HDL.6 The cause of the neuropathy is unknown but may be related to impaired ability to remove toxic substances (e.g., lipid and associated byproducts) from the axon.

There is no treatment for Tangier disease. Attention is directed toward reducing the cardiovascular risk associated with elevated triglyceride and low-density lipoprotein levels by treatment with lipid-lowering agents.

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Dec 16, 2016 | Posted by in NEUROLOGY | Comments Off on Stepwise Facial and Upper Limb Weakness and Small Fiber Sensory Loss—Tangier Disease

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