Postmortem findings in two familial amyloidosis patients with transthyretin variant Asp38Ala

Abstract

Postmortem findings in 2 familial amyloidosis patients with the transthyretin variant (ATTR), Asp38Ala, are described Both showed cardiac failure, and progressive peripheral and autonomic neuropathy and died at the ages 82 and 57, respectively. TTR immunoreactive amyloid deposition was observed to be extensive in the myocardium, peripheral nerves, sympathetic ganglia and gastrointestinal tract. The pulmonary parenchyma was also diffusely involved, but renal glomeruli, follicular tissues of the thyroid, and the leptomeninges and subarachnoidal vessels of the central nervous system showed little deposition. The latter findings are not usually seen in the patients with ATTR Val30Met, the most common form of familial amyloidosis. Additionally, the clinicopathological findings of familial amyloidosis with ATTR Asp38Ala seem to vary in the different individuals.

Familial amyloid polyneuropathy

“…However, amyloid deposits in the leptomeninges, and especially around blood vessels penetrating the CNS, can occasionally lead to ischemic or hemorrhagic strokes, dementia, hemiparesis and seizures. Most symptomatic CNS involvements have been reported in non-Val30Met mutations [9][10][11][12][13][14], although they occur also in the Val30Met mutation [15,16]. The three patients of this series who went to autopsy carried the Val30Met mutation, and had conspicuous, although asymptomatic, leptomeningeal amyloid deposits predominantly around blood vessels.…”

Familial Transthyretin Amyloidosis with Variant Asp38Ala Presenting with Orthostatic Hypotension and Chronic Diarrhea

“…On the other hand, ATTR Asp38Ala is clinically characterized by progressive cardiac dysfunction, and peripheral somatic and autonomic neuropathy 19-21). Yazak et al19) reported postmortem findings for two ATTR Asp38Ala cases, in which amyloid deposition was observed extensively in myocardium, peripheral nerves, sympathetic ganglia, and in the gastrointestinal tract.…”

A Rare Lung Nodule Consisting of Adenocarcinoma and Amyloid Deposition in a Patient with Primary Systemic AL Amyloidosis

“…In both types amyloid nodules are commonly located in the subpleural spaces, frequently showing bilateral distribution (1). The latter is a manifestation of systemic amyloidosis, the major underlying disorder of which is AL amyloidosis (6, 7), while ATTR-or AA-type systemic amyloidosis only very occasionally involves pulmonary tissues (8,9). In the localized form of AL amyloidosis the amyloidogenic light chains are produced by a local, tissue-based lymphoplasmacytic dyscrasia (10), while in systemic AL amyloidosis a circulating monoclonal protein is an amyloid precursor and amyloid deposition on vascular walls in the affected organ is a characteristic finding (11).…”