Familial amyloid with a transthyretin leucine 33 mutation presenting with ascites

Abstract

A 65-year-old female presented with symptomatic ascites. Light and electron microscopy examination of omental and peritoneal tissue obtained at exploratory laparotomy revealed amyloidosis. Immunochemical studies of the amyloid tissue showed positive staining with antibodies to transthyretin. Polymerase chain reaction (PCR), single strand conformation polymorphism analysis, and direct DNA sequencing demonstrated a transthyretin phenylalanine to leucine substitution at codon 33. This is only the second reported case of a transthyretin leucine 33 mutation. Moreover, this patient is unique among cases of transthyretin-associated amyloidosis with the clinical presentation of ascites. Am.

Transthyretin-related familial amyloid polyneuropathy (ATTR-FAP) in Poland — genetic and clinical presentation

“…Typical clinical features associated with the Phe33Leu TTR mutation include axonal polyneuropathy with marked autonomic involvement and cardiomyopathy with the onset of symptoms in middle age. Bilateral carpal tunnel syndrome (CTS) was also reported [3,19]. The clinical features in our families were consistent with previous reports.…”

“…Phe33Leu is a rare mutation, only ever reported in families from the Baltic regions (unrelated Polish-American patients) [3][4][5]18] Sweden [19], Taiwan [20], China [21] and Israel [22].…”

“…To date, no ATTR-FAP cases from Poland have been published, although there are some reports of ATTR-FAP patients of Polish origin, who were identified in other countries [3][4][5][6]. Here, we describe retrospective studies of ATTR-FAP families diagnosed in Poland.…”

Spectrum of transthyretin gene mutations and clinical characteristics of Polish patients with cardiac transthyretin amyloidosis

“…Position 53 of TTR protein is not directly involved in the formation of the transthyretin tetramer, however, loss of an aromatic ring associated with phenylalanine, may change the molecule conformation and lead to fibril formation [20]. The p.Phe53Leu TTR mutation was described previously only in 7 unrelated families including 2 American families of Polish descent and single Swedish, Taiwanese, Chinese, Hungarian and Israeli families [19][20][21][22][23][24][25]. This mutation was associated mostly with late-onset, progressive polyneuropathy and simultaneous presentation of severe cardiomyopathy.…”

Hereditary transthyretin amyloidosis caused by the rare Phe33Leu mutation

“…It was initially seen in an American male of Polish-Lithuanian decent who presented at age 53 with rapidly progressing peripheral polyneuropathy and orthostatic hypotension, later developing cardiomyopathy 9 10. The second was a 65-year-old Polish-American female who presented with ascites but was diagnosed with asymptomatic cardiomyopathy and later died of unknown cause 11. The third case was a man from northern Sweden who had previously undergone surgery for bilateral carpal tunnel syndrome and presented with painful peripheral polyneuropathy at age 46.…”