ABSTRACT
Hereditary transthyretin amyloidosis is a multisystemic autosomal dominant genetic disorder characterized by progressive distal sensory-motor polyneuropathy or restrictive cardiomyopathy, secondary to amyloid deposits. Its pathogenesis lies in the TTR gene mutation, and the Val50Met mutation is the most frequent. Patients have significant differences in the onset and severity of clinical presentation according to their country of origin. The diagnosis of this pathology is complex, even more in countries where it is not considered endemic. However, early suspicion and management are essential to improve survival and avoid unnecessary diagnostic and therapeutic strategies. We report a 69-year-old woman who presented a sensory-motor polyneuropathy, predominantly sensory, associated with distal neuropathic pain and bilateral vitritis. The history of her Italian father with polyneuropathy of unspecified etiology stood out. A vitreous biopsy identified amyloid substance deposits (congo red positive). These were also confirmed on a superficial peroneal nerve biopsy. During the etiological study of her polyneuropathy, an increased Kappa/Lambda index of 2.55 mg/L stood out. Therefore, light chain amyloidosis was suspected, and chemotherapy treatment was indicated without favorable response. After 10 years of progressive neurological and ophthalmological involvement, a genetic study confirmed the first case of late-onset hereditary transthyretin amyloidosis Val50Met with polyneuropathy in Chile.
Subject(s)
Humans , Female , Aged , Polyneuropathies/etiology , Polyneuropathies/genetics , Amyloid Neuropathies, Familial/complications , Amyloid Neuropathies, Familial/diagnosis , Amyloid Neuropathies, Familial/genetics , Prealbumin/genetics , MutationSubject(s)
Humans , Male , Female , Aged , Gait Ataxia/genetics , Polyneuropathies/genetics , Aged, 80 and over , Chronic Disease , Electromyography , ElectrophysiologyABSTRACT
In view of therapeutic implications and problems in clinical diagnosis, this study sought to evaluate and identify histopathological features of acquired inflammatory demyelinating neuropathies and hereditary demyelinating neuropathies. Sural nerve biopsies from 41 patients of demyelinating neuropathies, diagnosed on the basis of accepted clinical criteria, were studied using routine histological staining and special stains for myelin and axons. Chronic inflammatory neuropathies differed from the acute ones in having more endoneurial connective tissue, less of subperineurial oedema and presence of axonal sprouting and occasional onion bulb formation. Acquired neuropathies differed from hereditary neuropathies in having a more localized involvement, endoneurial oedema and variable inflammatory cell infiltration, while in hereditary neuropathies Schwann cell proliferation was diffuse and relatively uniform. The frequency and degree of nerve thickening was more in hereditary neuropathy. Evidence of inflammation was not universal, both in the acute and the chronic inflammatory demyelinating neuropathies. Histopathological examination is essential as the clinical and electrophysiological features alone may not offer definitive diagnosis.