Amyloid neuropathy

Neuropathies can result from mutations that alter the structure or level of expression of PNS myelin proteins (e.g. overexpression of PMP22 in Charcot-Marie-Tooth syndrome (CMT) type 1A), the metabolism of myelin lipids (e.g. metachromatic leukodystrophy), or the capacity of PNS neurons to support their axons in patients with CMT caused by mutations of KIF1B [4] or NF-L [5, 6]. Both acquired and inherited amyloid neuropathies can result from the deposition of poorly soluble proteins, for example cryoglobulins or mutant transthyretins, in and around endoneurial bloodvessels [7-9]. 

Miller-Fisher syndrome, Bickerstaff s brainstem encephalitis Acute motor axonal neuropathy Immunoglobulin light-chain amyloid neuropathy Cryoglobulinemic neuropathy... 

Several forms of neuropathy occur in patients with plasma cell dyscrasias. In light chain amyloid neuropathy, insoluble aggregates of immunoglobulin light chains... 

As a basis of various pathologic conditions, about 40 or more different proteins each can self-aggregate to form the "primary protein" of an amyloid. For example, in amyloid peripheral neuropathies the deposited extracellular amyloid often contains (a) the variable portion of immunoglobulin light chain in some B-lymphocyte dyscrasias, or (b) mutant transthyretin in some autosomal dominant hereditary amyloid neuropathies. 

Engel WK, Trotter JL. (1979) Plasma-cell dyscrasic amyloid neuropathy a parasparafucile phenomenon In Serratrice G, Roux H (eds). Peroneal Atrophies and Related Disorders. Masson Publishing Co, New York, pp. 339-347. 

Vignette 17. Amyloid neuropathy, dysimmune, due to B-lymphocyte dyscrasia... 

Vignette 18. Amyloid neuropathy, hereditary, due to transthyretin mutation... 

An hereditary amyloid neuropathy should also be considered in an older patient with a sensory greater than motor polyneuropathy, especially if there is also cardiac involvement (e.g., cardiomyopathy) and/or autonomic dysfunction. There could be an autosomal dominant genetic pattern of similarly affected persons—e.g., if the amyloid is caused by the TTR-Met30 mutation of transthyretin (TTR), that is easily tested for. As with other sensory more than motor polyneuropathies, all treatable causes such as dysim-mune, anti-MAG, and diabetes-2, should be sought. A soft-tissue radionuclide scan, which we introduced... 

Occasionally the nervous system becomes involved in myelomatosis, and a number of cases have been reported. The lesions in these patients include compression of neural structures by myeloma tissue or collapsed vertebra, herpes zoster, and amyloid infiltration of the peripheral nervous system. Although uncommon, a peripheral neuromyopathy in which there is no direct involvement of nerves or nerve roots has been reported, but the association of multiple myeloma with neuropathy and osteosclerotic lesion is rarer and even more unusual. Osuntokun et al. (05) has reported such a patient in Africa whose outstanding clinical features were widespread neuromyopathy associated with multiple myeloma, and general-... 

One type of familial amyloidosis first identified in the Finnish population is caused by deposition of gelsolin (Maury et al., 2000 Maury et al., 2001). This Finnish type familial amyloidosis (FAF) is a hereditable autosomal dominant amyloid polyneuropathy, characterized by corneal lattice dystrophy, progressive cranial and peripheral neuropathy as well as skin changes (Chen et al., 2001 Maury et al., 2001). 

Transthyretin amyloidosis (also called familial amyloid polyneuropathy) is an autosomal dominant syndrome characterized by peripheral neuropathy. This disease results from one of five mutations identified thus far in the gene for transthyretin. Transthyretin is also called prealbumin (although it has no structural relationship to albumin) because it migrates ahead of albumin in standard electrophoresis at pH 8.6. Transthyretin is synthesized in the liver and is a normal plasma protein with a concentration of 20-40 mg/dL. It transports thyroxine and retinol binding protein (Chapter 38). The concentration of transthyretin is significantly decreased in malnutrition and plasma levels are diagnostic of disorders of malnutrition (Chapter 17). 

Secondary AA Serum amyloid A protein neurologic, soft tissues, lungs, endocrine Kidney, GI, neuropathy—... 

Amyloid diseases are typically associated with aging, although some genetic neuropathy forms can begin earlier. Not yet clarified are two questions (a) what starts the accumulation of misfolded proteins that lead to the amyloidic process and (b) how do the amyloidic processes impair function of normal cells, i.e. what is the molecular mechanism of amyloid-associated cellular toxicity ... 

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