Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis
-
Transthyretin (ATTR) amyloidosis is often diagnosed in an advanced stage, when irreversible cardiac damage has occurred. Lumbar spinal stenosis (LSS) may precede cardiac ATTR amyloidosis by many years, offering the opportunity to detect ATTR already at the time of LSS surgery. We prospectively assessed the prevalence of ATTR in the ligamentum flavum by tissue biopsy in patients aged >50 years undergoing surgery for LSS. ⋯ Amyloid, mostly of the ATTR subtype, was found in four out of five patients with LSS and is associated with age and ligamentum flavum thickness. Histopathological work-up of ligamentum flavum might inform future decision making.
-
Hereditary 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. ⋯ We 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.
-
Immunoglobulin light chain (LC) amyloidosis is a life-threatening disease complicated by vast numbers of patient-specific mutations. We explored 14 patient-derived and engineered proteins related to κ1-family germline genes IGKVLD-33*01 and IGKVLD-39*01. ⋯ The results suggest distinct amyloidogenic pathways for closely related LCs and point to the complementarity-defining regions CDR1 and CDR3, linked via the conserved internal disulfide, as key factors in amyloid formation.