New clinical forms of hereditary apoA-I amyloidosis entail both glomerular and retinal amyloidosis

Novel clinical manifestations and treatment of hereditary apoA-I amyloidosis: when a good protein turns bad

“…Although neurodegenerative amyloidoses such as Alzheimer, Parkinson, and prion diseases received much attention in recent years, systemic amyloidoses, which can affect various organs except the brain and afflict tens of thousands of patients worldwide, remain relatively underexplored and underdiagnosed. 3 Pioneering studies by several teams including Valleix and colleagues 4,5 help to fill this gap. The diagnostics of systemic amyloidoses remain challenging because amyloid deposits can impair a wide range of organs (kidneys, liver, heart, spleen, testes, nerves, etc.…”

“…), the impairment may range from mild to severe, and the deposition of unrelated proteins often leads to overlapping clinical presentations. [3][4][5] Fibril typing to identify the protein precursor of amyloid is paramount to devising the appropriate treatment strategy. For example, bone marrow transplantation can be performed to halt the generation of the aberrant immunoglobulin light chains and thereby block the progression of light chain amyloidosis.…”

“…In contrast, liver transplantation can be warranted to block the generation of the aberrant protein variants in hereditary apolipoprotein A-I (apoA-I) amyloidosis (AApoAI) described by Colombat et al in this issue. 5 Exchangeable apolipoproteins are prominent in amyloidoses. These proteins are synthesized by the liver and gut and enter the circulation in the form of lipoprotein nanoparticles.…”

“…8 The latter form is in the focus of the present study. 5 AApoAI is an autosomal dominant disorder wherein 9-to 11-kDa Nterminal fragments of the variant protein deposit as fibers in kidneys, liver, nerves, heart, testes, spleen, skin, and other organs, causing organ damage 5,7 ( Figure 1). The list of affected organs is probably incomplete; importantly, the present study adds retina to this list.…”

“…The list of affected organs is probably incomplete; importantly, the present study adds retina to this list. 5 The clinical presentation of AApoAI can vary from mild to severe, depending in part on the location of the mutation, 7 which complicates the diagnostics. More than 20 amyloidogenic APOA1 gene mutations have been identified to date.…”