4. Cranial neuropathy with corneal lattice dystrophy and facial palsies. This unusual form of amyloid neuropathy was first described in three Finnish families by Meretoja, hence the label “Finnish type.” Subsequently, it was reported from several different parts of the world in families of non-Finnish heritage. The disease usually begins in the third decade with lattice corneal dystrophy. Vitreous opacities are not observed, and visual acuity is little affected. Peripheral neuropathy may not be evident until the fifth decade, at which time the facial nerves, particularly their upper branches, become affected. The nerves of the limbs are involved even later and to a much lesser extent than in other amyloid neuropathies. In advanced cases there is a distinctive appearance of excessive skin folds about the face, facial diparesis, dysarthria, spasticity, and dense loss of posterior column function. At postmortem examination, deposits of amyloid are found in virtually every organ, mainly in the kidneys and blood vessels and in the perineurium of affected nerves.
The amyloid fibrils are derived from the protein gelsolin. The latter is normally an actin-binding protein, but it is also an important constituent of basement membranes, which may explain the deposition of amyloid in the cornea and skin.
Diagnosis of familial amyloid neuropathy When the characteristic painful small-fiber type of sensory disturbance and autonomic changes are coupled with a family history of the same constellation, the diagnosis is not difficult. As noted in the earlier section on the acquired paraproteinemic neuropathy, the presence of a monoclonal (rarely polyclonal) immunoglobulin in the blood is found in only a limited number of patients with familial amyloid cases and it is usually just above the upper limit of normal for the immunoglobulin subclass. Otherwise the two types of amyloid diseases, FA and AL, are quite similar and, indeed, approximately 10 percent of cases considered by history and examination to be acquired will be found to have the genetic disorder (Lachmann et al 2002). The situation has been clarified by the availability of gene sequencing to detect mutations in transthyretin that are related to amyloidosis.
Pathologic findings Amyloid deposits are demonstrable in the walls of blood vessels, the interstitial (endoneurial) tissues of the peripheral somatic and autonomic nerves, and in the spinal and autonomic ganglia and roots. There is a loss of nerve fibers, the unmyelinated and small myelinated fibers being more depleted than the large myelinated ones. The anterior horn and sympathetic ganglion cells are swollen and chromatolyzed because of involvement of their axons, and the posterior columns of the spinal cord degenerate, also on a secondary basis.
The pathogenesis of the fiber loss in familial amyloidosis, as in the acquired type, is not fully understood. On the basis of their findings in a sporadic case of amyloid polyneuropathy with diabetes mellitus, Kernohan and Woltman suggested that amyloid deposits in the walls of the small arteries and arterioles interfered with the blood supply in the nerves and that amyloid neuropathy is essentially an ischemic process. In other cases, however, the vascular changes are relatively slight and the degeneration of the nerve fibers appears to be related to their compression and distortion by the endoneurial deposits of amyloid or, alternatively, there may be a direct toxic effect of the embedded amyloid. Amyloid also deposits in the tongue, gums, heart, gastrointestinal tract, kidneys, and many other organs, where it may act as a tissue toxin or has a mechanically disrupting effect on cells.