Familial amyloidotic polyneuropathy (ATTR Val30Met) with widespread cerebral amyloid angiopathy and lethal cerebral hemorrhage

Abstract

We report an autopsy case of familial amyloidotic polyneuropathy (FAP) with cerebral hemorrhage. A 38-year-old woman with a typical FAP pedigree started developing severe diarrhea and sensori-motor polyneuropathy at the age of 28 years; autonomic nervous system, heart and renal dysfunction manifested themselves in the following years. Genetic analysis revealed a single amino acid substitution at codon 30 of transthyretin (ATTR Val30Met). Ten years after her initial symptoms, the patient died of a sudden convulsive attack and respiratory failure. Autopsy revealed lethal cerebral hemorrhages and uremic lungs. Histochemical and immunohistochemical analyses revealed TTR-derived amyloid protein in every tissue examined, particularly in glomeruli and peripheral vessels. Severe meningo-cerebrovascular amyloidosis was also detected. Because uremia causes oxidative damage to the vascular system and amyloid formation is closely associated with oxidative stress, it is possible that uremic endothelial damage facilitated an unusual cerebral amyloid deposition. In typical FAP (ATTR Val30Met), cerebral amyloid angiopathy does not usually have clinical manifestations. However, cerebral amyloid angiopathy should be considered to explain FAP symptoms when some risk factors such as uremic vascular damage are accompanying features.

Clinical and histopathological features of progressive-type familial amyloidotic polyneuropathy with TTR Lys54

“…The loss of anterior horn cells observed in our case is thought to have the same significance. Various involvements of the CNS have been reported, including leptomeningeal deposition or severe meningocerebrovascular amyloidosis [23]. In our patient, slight deposition was observed in the blood vessel walls in the leptomeninges, but not in the brain parenchyma including blood vessels.…”

Tissue Distribution, Biochemical Properties, and Transmission of Mouse Type A AApoAII Amyloid Fibrils

“…28,29 We found a characteristic tissue distribution of amyloid deposition in BDF1 and C57BL/6 mice, which showed severe depositions in the intestine and tongue but no depositions in the liver and spleen, where major amyloid deposits were observed in the Apoa2 c strains. Similar observations have been reported for human hereditary amyloidosis.…”

Energetic Characteristics of the New Transthyretin Variant A25T May Explain Its Atypical Central Nervous System Pathology

“…More worrisome is that amyloid deposition on subarachnoid vessels and leptomeninges was found in a patient with V30M FAP (Ushiyama et al, 1991). Although CNS involvement in V30M FAP is not generally considered to be clinically significant, three reports question this generally held perception (Herrick et al, 1996;Horta et al, 1964;Sakashita et al, 2001). Therefore, CNS amyloidosis could be a future problem for the Ͼ 500 patients who have received V30M transplantation (Familial Amyloidotic Polyneuropathy World Transplant Register, www.fapwtr.org/).…”