Hereditary gelsolin amyloidosis: a rare cause of cranial, peripheral and autonomic neuropathies linked to D187N and Y447H substitutions

IntroductionHereditary gelsolin (AGel) amyloidosis is a systemic disease that is characterised by neurologic, ophthalmologic, dermatologic, and other organ involvements. We describe the clinical features with a focus on neurological manifestations in a cohort of patients with AGel amyloidosis referred to the Amyloidosis Centre in the United States.MethodsFifteen patients with AGel amyloidosis were included in the study between 2005 and 2022 with the permission of the Institutional Review Board. Data were collected from the prospectively maintained clinical database, electronic medical records and telephone interviews.ResultsNeurologic manifestations were featured in 15 patients: cranial neuropathy in 93%, peripheral and autonomic neuropathy in 57% and bilateral carpal tunnel syndrome in 73% of cases. A novel p.Y474H gelsolin variant featured a unique clinical phenotype that differed from the one associated with the most common variant of AGel amyloidosis.DiscussionWe report high rates of cranial and peripheral neuropathy, carpal tunnel syndrome and autonomic dysfunction in patients with systemic AGel amyloidosis. The awareness of these features will enable earlier diagnosis and timely screening for end-organ dysfunction. The characterisation of pathophysiology will assist the development of therapeutic options in AGel amyloidosis.

Automated summary

This article describes the clinical features of hereditary gelsolin (AGel) amyloidosis, a systemic disease characterized by neurological, ophthalmological, dermatological, and other organ involvements. Neurological manifestations were observed in 15 patients, including cranial neuropathy, peripheral neuropathy, and carpal tunnel syndrome. A novel gelsolin variant was identified and associated with a unique clinical phenotype.