Two novel APOA1 gene mutations in a Japanese renal transplant recipient with recurrent apolipoprotein A‐I related amyloidosis

Abstract

Apolipoprotein A-I amyloidosis is a rare, autosomal dominant disorder of APOA-1 gene characterized by the deposition of apolipoprotein A-I in various organs and can be classified into either hereditary or nonhereditary form in the absence of a family history. Renal disease caused by Apolipoprotein A-I amyloidosis commonly manifested as slowly progressive renal function impairment without heavy proteinuria. Apolipoprotein A-I-related amyloidosis of kidney is of pathogenetic interest because the renal failure is due to peritubular and interstitial amyloid deposits without glomerular deposits. Tubulointerstitial lesion of amyloid deposits was diagnosed in half of carriers of APOA1 gene mutation, only 13% of patients progressed to renal failure requiring hemodialysis or kidney transplantation. Recurrence of apolipoprotein A-I-related amyloidosis after kidney transplantation is very rare. We report a case of a 63-year-old Japanese female without a family history of kidney and/or liver disease who showed slowly progressive renal graft dysfunction without overt proteinuria. Graft biopsy revealed characteristic Congo red stain positive amyloid deposits localized in the renal interstitial area. No glomerular, vascular and tubular amyloid deposits were noted. Laser microdissection-liquid chromatography tandem mass spectrometry-based proteomic analysis elucidated the type of amyloidosis as apolipoprotein A-I amyloidosis. Genetic analysis of DNA sequence study revealed two novel APOA1 gene mutations of Leu202Arg and Lys262Asn. This is a first and very rare case report of the recurrence of non-familial hereditary apolipoprotein A-I amyloidosis in Japanese transplant recipient.

The amyloid proteome: a systematic review and proposal of a protein classification system

“…Although Apo-AIV can occur as a fibril protein (Sethi et al 2012;Dasari et al 2016), it is also considered an amyloid signature protein (Vrana et al 2014). Similarly, Apo-AI and its gene variants can either be amyloid fibril proteins (Horike et al 2018), or regular constituents in fat tissue; therefore, they are not suited as an amyloid surrogate marker in fat aspirates (Vrana et al 2014). In our literature review, Apo-AI was found in 53% (66/125) of samples that were categorized as non-Apo-AI amyloidosis.…”

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

“…Until a patient with fibrinogen-related amyloidosis (AFib amyloidosis) was reported in 2015 ( 19 ), no case of hereditary non-neuropathic systemic amyloidosis had been reported in Japan. As for AApoAI amyloidosis, only one patient with two apoAI variants (L202R and K262N) has recently been described ( 17 ). A 63-year-old Japanese woman underwent renal transplantation due to amyloid nephropathy ( 17 ).…”

Phosphatidylethanolamine accelerates aggregation of the amyloidogenic N‐terminal fragment of apoA‐I

“…The hereditary apoA-I amyloidosis is characterized by the deposition of the N-terminal 80-100-residue fragments of the variant protein as amyloid fibrils in peripheral organs such as heart, liver, kidneys, or gastrointestinal tract [4][5][6]. To date, over 20 naturally occurring mutations in human apoA-I associated with familial amyloid polyneuropathy have been reported [7][8][9]. For some apoA-I amyloidoses, it is known that a preferential fibril deposition in certain tissues and organs occurs such that the amyloidogenc apoA-I variants with mutations clustered in residues 1-75 predominantly deposit in kidneys and liver [7].…”