Renal ApoA-1 Amyloidosis with Glu34Lys Mutation and Intra-amyloid Lipid Accumulation

Abstract

Apolipoprotein A-1 (ApoA-1) amyloidosis occurs as a nonhereditary condition in atherosclerotic plaques, but it can also manifest as a hereditary disorder caused by mutations of the APOA1 gene. Hereditary ApoA-1 amyloidosis presents with diverse organ involvement based on the position of the mutation. We describe a case of ApoA-1 amyloidosis with a Glu34Lys mutation; testicular, conjunctival, and renal involvement; and the notable finding of lipid deposition within the amyloid deposits.

Giant Hepatomegaly with Spleno-testicular Enlargement in a Patient with Apolipoprotein A-I Amyloidosis: An Uncommon Type of Amyloidosis in Japan

“…Regarding the mutation-phenotype correlation, Eriksson et al reported that patients with mutations in codons 1-75 (amino terminal) were likely to develop hepatic and renal amyloidosis, while carriers of mutations in residues 173-178 (carboxyl terminal) mainly develop cardiac, laryngeal, and cutaneous amyloidosis ( 5 ). This is consistent with our case and the two reported cases with an E34K mutation ( 15 , 21 ).…”

“…The E34K mutation detected in our patient was located outside of these hot-spot regions, and only two cases with the same mutation have been reported (15,21). The first case described with this variant was a 29-year-old woman who suffered from amyloid nephropathy (15), and the sec-ond case was a 26-year-old man who had infertility due to testicular amyloid and amyloid nephropathy (21). Neither of them had apparent clinical amyloid hepatopathy, as was seen in our patient, but the first case was suspected of having amyloid deposits in the liver and spleen by radiolabeled SAP scintigraphy (15).…”

“…The E34K mutation detected in our patient was located outside of these hot-spot regions, and only two cases with the same mutation have been reported (15,21). The first case described with this variant was a 29-year-old woman who suffered from amyloid nephropathy (15), and the sec-ond case was a 26-year-old man who had infertility due to testicular amyloid and amyloid nephropathy (21).…”

Molecular basis for a novel systemic form of human hereditary apoA-I amyloidosis with vision loss

“…Therefore, our study provides the first detailed clinicopathological investigation of ophthalmic abnormalities in AApoAI and suggests that retinal amyloidosis should be considered in AApoAI cases with ophthalmic manifestations of undetermined origin. This idea is supported by the previous report of unexplained ophthalmic manifestations in one sporadic Glu34Lys AApoAI patient (Andeen et al, 2014) and in two additional AApoAI patients from another kindred carrying the c.280-288del in-frame mutation (Persey et al, 1998); these retinal abnormalities remained unexplored and their causal link with amyloidosis was not established. Taken together with the current study, these reports prompt us to propose to search for choroidal amyloid angiopathy in all suspected AApoAI patients to detect the onset of symptoms at the earliest possible stage, which is crucial for optimal therapeutic management and visual prognosis of the patients.…”

“…To-date, two sporadic cases of Glu34Lys AApoAI have been reported, both presenting with proteinuria and chronic kidney disease (Rowczenio et al, 2011;Andeen et al, 2014); one case also involved testicular and conjunctival amyloidosis (Andeen et al, 2014). A detailed anatomopathological study of a renal specimen has been performed for one Glu34Lys carrier, demonstrating unusual amyloid deposits in the glomeruli (Andeen et al, 2014). Clinical and pathological renal features of three additional Glu34Lys patients described in the current study definitively establish the causal role of Glu34Lys apoA-I in glomerular amyloid deposition.…”