Familial amyloidotic polyneuropathy type IV – gelsolin amyloidosis

Abstract

Familial amyloidotic polyneuropathy type IV, or Gelsolin amyloidosis (GA), is a rare condition caused by G654A or G654T mutation in gelsolin gene at 9q32-34. Gelsolin seems essential in many processes, including inflammation, cell motility, neural recovery, apoptosis and even carcinogenesis. So far reported from many European countries, USA, Japan, Iran and Brazil, GA is probably still underdiagnosed. The typical diagnostic triad includes corneal lattice dystrophy, progressive bilateral facial paralysis and cutis laxa. Patients present with progressive cranial and peripheral neuropathy, eye symptoms, usually mild proteinuria, and cardiac conductive disturbances with age. Central nervous system symptoms are rare. Gelsolin amyloid collection in tissues is widespread. To date, treatment is symptomatic. Regular check-ups with ophthalmologist are recommended. Plastic surgery relieves the functional symptoms caused by facial paralysis and loose, hanging facial skin.

MR Imaging Features of the Cerebellum in Adult-Onset Neuronal Intranuclear Inclusion Disease: 8 Cases

“…22 Like the high-intensity signal along the corticomedullary junction on DWI, this lesion may also help clinicians distinguish between NIID and clinically similar diseases such as gelsolin amyloidosis, which can present with neuropathy, ataxia, and dementia. 23 The limitation of this study was that in no patients was brain pathology obtained. However, in both sporadic and familial cases of NIID, it was reported that nuclear inclusions detected by skin biopsy are morphologically and immunohistochemically identical to those reported for NIID inclusions in neuronal cells.…”

On the Role of Aggregation Prone Regions in Protein Evolution, Stability, and Enzymatic Catalysis: Insights from Diverse Analyses

“…PDB entries for these proteins are 1FUK (C-terminal domain of yeast initiation factor 4A), 1JEO (Hypothetical protein MJ1247 from Methanococcus jannaschii ), 1KCQ (Human Gelsolin Domain 2), 1OW1 (SPOC domain of human transcriptional factor SHARP), 1SK7 (Hypothetical protein pa-HO from Pseudomonas aeruginosa ), 1Z77 (Transcriptional regulator (tetR family) from Thermotoga maritima ), 2D4F (Human β-microglobulin), 2VB1 (Hen Egg White Lysozyme) and 3NR5 (Human RNA polymerase III transcription repressor Maf1). Note that Hen egg-white lysozyme, human β-microglobulin and human gelsolin are well studied amyloidogenic proteins [61]–[63].…”

Familial progressive bilateral facial paralysis in Finnish type hereditary amyloidosis

“…It is characterised by the triad of lattice corneal dystrophy type II, cutis laxa and progressive bilateral facial paralysis 1. It is more common among Finnish people, and most cases have the pathogenic mutation found in our patient.…”

“…It is more common among Finnish people, and most cases have the pathogenic mutation found in our patient. Patients may have cardiomyopathy, chronic renal failure, nephrotic syndrome, gastrointestinal complaints and variable autonomic disturbances, although these are less common than in TTR -related familial amyloidotic polyneuropathy 1. Although very rare, Finnish type amyloidosis should be considered in patients presenting with slowly progressive bilateral facial weakness, where the differential diagnosis would include Lyme disease, sarcoidosis, Melkersson-Rosenthal syndrome and neurolymphomatosis 1 2…”