Vitreous amyloidosis with autonomic neuropathy of the digestive tract associated with a novel transthyretin p.Gly87Arg variant in a Bangladeshi patient: a case report

Abstract

BackgroundHereditary transthyretin amyloidosis is an autosomal dominant inherited disorder, first described in families with sensorimotor and autonomic neuropathy. Since its first description, more than 120 amyloidogenic transthyretin mutations have been reported with various geographic distributions and associated with a wide range of phenotypes involving the peripheral nerve, the heart, the gastrointestinal tract, the eyes, the central nervous system, or the kidneys. In some cases of transthyretin amyloidosis, the first clinical manifestation is vitreous opacity.Case presentationA 46-year-old Bangladeshi woman presented with vitreous amyloidosis and progressive autonomic neuropathy of the digestive tract as initial clinical manifestations, with no clinical evidence of cardiac, renal, central nervous system, or peripheral nerve dysfunction. A novel transthyretin mutation, p.Gly87Arg, was identified in the heterozygous state in this proband of Bangladeshi origin. Histological examination of accessory salivary glands and gastric biopsies revealed Congo-red-positive deposits. Laser microdissection of salivary gland Congo-red deposits and tandem mass spectrometry-based proteomic analysis identified the mutated transthyretin peptide containing the arginine residue at position 87 of the mature protein.ConclusionsVitreous amyloidosis should be considered a differential diagnosis of uveitis, in particular transthyretin amyloidosis. Proteomics data from our case, consistent with the genetic findings, highly suggests that this new p.Gly87Arg variant is amyloidogenic. Here, we described the second case of transthyretin amyloidosis reported in a Bangladeshi patient.

Ophthalmological manifestations of hereditary transthyretin amyloidosis

“…They can be seen in patients with late-onset neuropathy, leptomeningeal and central nervous system involvement, or, more rarely, in those with ophthalmological involvement alone (24) . Vitreous amyloidosis is an important differential diagnosis of uveitis (53) .…”

“…Patients usually report blurred vision and floaters, with a variable degree of painless vision loss progressing from months to years and dependent on amyloid deposition density (53,54) . Fundoscopy reveals yellowish-white glass-wool vitreous opacity consistent with amyloid deposits (53,55) .…”

“…Patients usually report blurred vision and floaters, with a variable degree of painless vision loss progressing from months to years and dependent on amyloid deposition density (53,54) . Fundoscopy reveals yellowish-white glass-wool vitreous opacity consistent with amyloid deposits (53,55) . Some authors reported that vitreous opacities are the most common ophthalmological change in late-onset Val30Met ATTRv amyloidosis with at least 4 types of deposits: lentis, fibrils, spherical opacities, and prevascular opacities (36) .…”