Exploring clinical variability in gelsolin amyloidosis: Brazilian family case study with confocal microscopy

Genetic mutations or inflammatory, degenerative, or neoplastic conditions can trigger amyloidosis. Hereditary gelsolin amyloidosis is a genetic disorder primarily marked by amyloid fibrils composed of misfolded gelsolin fragments.

We present three sisters with AGel amyloidosis, illustrating its clinical diversity. Patient 1, a 51-year-old, had bilateral ptosis, ocular discomfort, and dry eye syndrome due to cranial nerve involvement. Patient 2, a 53-year-old, experienced progressive bilateral visual impairment. Patient 3, a 50-year-old, exhibited right eye ectropion. Genetic analysis, with the identical mutation, heterozygous c.640G > A (p.Asp214Asn) mutation, confirmed AGel amyloidosis diagnoses, with common findings including lattice corneal amyloidosis, reduced corneal sensitivity, and recurrent corneal erosions. Neurological manifestations included ataxia and peripheral neuropathy, with skin abnormalities observed in patient 1. Ocular involvement severity and distribution varied among patients.

Common ocular and neurological manifestations validated AGel amyloidosis diagnoses, reinforcing its hereditary basis. Neurological symptoms highlighted the disorder's impact on various organ systems, while skin abnormalities contributed to ocular discomfort. Variable ocular involvement emphasized the disorder's heterogeneity. These patients emphasize hereditary gelsolin amyloidosis's clinical diversity and suggest potential environmental influences on disease expression. Genetic confirmation and confocal microscopy findings reaffirm the genetic basis while raising questions about assessing systemic disease severity, necessitating further investigation in larger cohorts. Ophthalmologists' specialized care is crucial for managing ocular symptoms, given the absence of a universal cure.