We reported a confirmed case of Fibrinogen Aa-chain (AFib) amyloidosis and conducted systematic review of the genetic and protein mutation types, clinical manifestations, diagnostic methods and treatment for patients with this disease worldwide. We reported a case of AFib amyloidosis. Meanwhile, a systematic search was performed using defined terms and updated up to November 2023 in the Wanfang, China National Knowledge Infrastructure, VIP, PubMed, and Web of Science databases to identify reported cases of AFib renal amyloidosis worldwide, according to PRISMA guidelines. A 46-year-old male patient was admitted for more than half a month because of oedematous lower limbs. Renal tissue mass spectrometry suggested an AFib type. Gene detection demonstrated that the patient carried the c.1673del (p.Lys558Argfs*10) locus heterozygous mutation of Fibrinogen Aα-chain gene (FGA). The patient was treated with haemodialysis because of uncontrollable hypertension. This systematic review comprised 46 cases. We found the onset age to be lower in women than in men (P < 0.05). All patients showed incipient symptoms including proteinuria; 10 (21.7%) patients progressed to end-stage renal disease (ESRD) or received renal replacement therapy (including dialysis and kidney transplantation) within 1 year; 18 (39.1%) patients progressed to ESRD or received renal replacement therapy within 1-5 years, and 4 (8.7%) patients did not progress to ESRD or received renal replacement therapy within 5 years. AFib amyloidosis progresses rapidly. The diagnosis of this disease is primarily based on renal biopsy, mass spectrometry, and molecular gene detection. Reducing proteinuria is the main method of treating this disease. CRD42024516146.

De Novo transplant amyloidosis denotes the condition when a patient develops amyloidosis after transplantation but had not been diagnosed with the disease prior to transplantation. The incidence of de novo amyloidosis in kidney transplants is rare, but few published case reports have described the occurrence of de novo Amyloid A protein (AA) and Light Chain (AL) amyloidosis. However, de novo hereditary fibrinogen A alpha chain (AFib) has not been previously reported. We present a 72-year-old man, a kidney transplant recipient, who developed progressive rise in his creatinine about 3 years after transplantation. He has long-standing diabetes mellitus type 2, obesity, and hypertension, so he did not have a kidney biopsy of his native kidneys prior to transplantation. A kidney transplant biopsy was done that showed amyloidosis. Mass spectrophotometry confirmed it as AFib amyloidosis. Genetic testing of the patient revealed that he has fibrinogen A alpha gene (FGA) point mutation with a p.E545V variant. Cardiac evaluation showed normal transthoracic echocardiogram. Cardiac magnetic resonance imaging (MRI) showed no involvement by amyloidosis. A peripheral nerve biopsy showed diabetic neuropathy. Thus, the kidney was the only organ involved by the disease. The kidney transplant was managed conservatively with blood pressure and diabetes control in addition to his usual immunosuppression regimen which was not altered. He is being treated with diuretics, angiotensin receptor inhibitors, and sodium glucose transport 2 inhibitors. Kidney transplant function exhibited only slow progression over 18 months since the diagnosis was confirmed. This slow progression is likely because the p.E545V point mutation variant is less aggressive than other gene deletion mutations and because our patient was judged to have been diagnosed early in the course of his disease. In this case report, we illustrate the findings and testing that confirmed the diagnosis of AFib amyloidosis. We summarize the clinical aspects, outcomes of the disease, and treatment options. We believe this case report is interesting because it is the first reported case of AFib amyloidosis in a kidney transplant recipient who was not known to have the disease prior to kidney transplantation. L’amyloïdose de novo de la transplantation désigne l’état d’un patient qui développe une amylose après une transplantation alors que la maladie n’avait pas été diagnostiquée avant l’intervention. L’incidence de l’amyloïdose de novo est rare en contexte de transplantation rénale, bien que la survenue d’amyloses AA et al de novo ait été décrite dans quelques rapports de cas publiés. L’amyloïdose de novo héréditaire de la chaîne alpha du fibrinogène A (FibA) n’a cependant jamais été rapportée. Nous présentons le cas d’un homme de 72 ans, receveur d’une greffe rénale, dont le taux de créatinine a augmenté progressivement environ trois ans après la transplantation. Le patient souffrait depuis longtemps de diabète de type 2, d’obésité et d’hypertension, de sorte qu’il n’avait pas subi de biopsie de ses reins d’origine avant la transplantation. Une biopsie du greffon rénal a montré une amyloïdose, laquelle a ultérieurement été typée par spectrophotométrie de masse comme étant une amyloïdose FibA. Des tests génétiques ont révélé que le patient présentait une mutation ponctuelle du gène alpha du fibrinogène (FGA) avec le variant p.E545V. L’échocardiogramme transthoracique du bilan cardiaque était normal. L’IRM cardiaque n’a montré aucune implication par amyloïdose, et une biopsie des nerfs périphériques a révélé une neuropathie diabétique. Ainsi, le rein était le seul organe touché par la maladie. La greffe rénale a été gérée de manière conservatrice, soit par le contrôle de la pression artérielle et du diabète en plus du schéma habituel d’immunosuppression, lequel n’a pas été modifié. Le patient est traité avec des diurétiques, des inhibiteurs des récepteurs de l’angiotensine et des inhibiteurs du cotransport sodium-glucose de type 2. La fonction du greffon n’a montré qu’une lente progression sur 18 mois depuis la confirmation du diagnostic. Cette lente progression est probablement due au fait que la mutation ponctuelle p.E545V est moins agressive que d’autres mutations de délétion du gène, et parce que notre patient a été jugé comme ayant reçu son diagnostic tôt dans l’évolution de sa maladie. Dans ce rapport de cas, nous mettons en évidence les résultats et tests qui ont confirmé le diagnostic d’amyloïdose FibA. Nous résumons les aspects cliniques, le pronostic de la maladie et les options de traitement. Ce rapport de cas est intéressant, car il s’agit du premier cas rapporté d’amyloïdose FibA chez un receveur d’une greffe rénale sans diagnostic connu de la maladie avant la transplantation.

Amyloidosis is a very heterogeneous disease. Correct diagnosis is extremely important because of the various treatment options for different types of amyloidosis. This study presents a case report and literature review of the misdiagnosis of fibrinogen Aα-chain amyloidosis (AFib amyloidosis). We report a 65-year-old man diagnosed with proteinuria in 2009. The kidney biopsy revealed the presence of Congo red-stained amyloid deposits. During differential diagnosis, amyloid deposits were discovered in adipose tissue and gingiva. Bone marrow trephine biopsy showed a predominance of lambda chains presenting plasmocytes. Based on performed medical examination, light chain amyloidosis was identified. Therefore, the patient received high-dose melphalan and underwent successful autologous peripheral blood stem cell transplantation. However, proteinuria, worsening of the kidneys' function, and incorrect levels of free light chains were still observed. In 2019, due to continuous treatment failure, a previously acquired kidney biopsy was examined by mass spectrometry, and numerous fibrinogen deposits were identified. Recommended DNA analysis revealed that the patient had AFib amyloidosis. Therefore, chemotherapy treatment was abandoned, and successful kidney transplantation was performed. Today, it is essential for medical practitioners to remember the possibility of rare and hereditary types of amyloidosis. There are multiple cases where a diagnosis was wrong or delayed because of the atypical course of the disease, the coexistence of another disease, and the rarity of AFib amyloidosis, and all of these reasons may result in the wrong treatment that will delay the right therapy. However, with the new, more precise diagnostics methods, such situations will become rare.

Fibrinogen A alpha-chain amyloidosis (AFib amyloidosis) is the most common form of hereditary renal amyloidosis in the United Kingdom and Europe, but has rarely been reported in Asia. In this study, we reported two AFib amyloidosis patients in China, reviewing the literature and summarizing main characteristics of AFib amyloidosis in Asia. Two unrelated Chinese patients were diagnosed with AFib amyloidosis by clinical presentation, renal biopsy, mass spectrometry and DNA sequencing in Peking University First Hospital of China from 2014 to 2016. Both of the patients presented with proteinuria, edema and hypertension. Renal biopsies of two patients showed extensive amyloid deposits (Congo red positive) in glomeruli, and focal tubulointerstitial amyloid deposits was also found in patient 1. Besides, hepatic involvement of amyloidosis has been detected by liver biopsy in patient 1. By electron microscopy, randomly arranged fibrils in a diameter of 8-12 nm was identified in mesangial matrix and subendothelial area of glomeruli. Immunohistochemistry demonstrated amyloid deposits were strongly positive for fibrinogen Aα in glomeruli and positive for LECT2 in the interstitium of renal medulla and the liver in Patient 1. Unevenly positive staining for both fibrinogen Aα and ApoA-I were found in Patient 2. Fibrinogen Aα was the most abundant amyloidogenic protein in both patients identified by laser microdissection and mass spectrometry-based proteomic analysis. Genetic analysis revealed the fibrinogen A a-chain gene (FGA) mutation in both patients, including a new deletion mutation [c.1639delA (p.Arg547Glyfs*21; NM_000508)] in Patient 2. Genetic analysis of the LECT2 gene in patient 1 revealed a codon change from ATC to GTC at position 172 [c.172A>G (p.Ile58Val; NM_002302)], which is a common polymorphism (SNP rs31517) in all ALECT2 amyloidosis patients. We reported two AFib amyloidosis patients in China, one of them coexisted with ALECT2 amyloidosis simultaneously.

Fibrinogen A α-chain amyloidosis (AFib amyloidosis) is a form of amyloidosis resulting from mutations in the fibrinogen A α-chain gene (FGA), causing progressive kidney disease leading to kidney failure. Treatment may include kidney transplantation (KT) or liver-kidney transplantation (LKT), but it is not clear what factors should guide this decision. The aim of this study was to characterize the natural history and long-term outcomes of this disease, with and without organ transplantation, among patients with AFib amyloidosis and various FGA variants. Case series. 32 patients with AFib amyloidosis diagnosed by genetic testing in France between 1983 and 2014, with a median follow-up of 93 (range, 4-192) months, were included. Median age at diagnosis was 51.5 (range, 12-77) years. Clinical presentation consisted of proteinuria (93%), hypertension (83%), and kidney failure (68%). Manifestations of kidney disease appeared on average at age 57 (range, 36-77) years in patients with the E526V variant, at age 45 (range, 12-59) years in those with the R554L variant (P<0.001), and at age 24.5 (range, 12-31) years in those with frameshift variants (P<0.001). KT was performed in 15 patients and LKT was performed in 4. In KT patients with the E526V variant, recurrence of AFib amyloidosis in the kidney graft was less common than with a non-E526V (R554L or frameshift) variant (22% vs 83%; P=0.03) and led to graft loss less frequently (33% vs 100%). Amyloid recurrence was not observed in patients after LKT. Analyses were based on clinically available historical data. Small number of patients with non-E526V and frameshift variants. Our study suggests phenotypic variability in the natural history of AFib amyloidosis, depending on the FGA mutation type. KT appears to be a viable option for patients with the most common E526V variant, whereas LKT may be a preferred option for patients with frameshift variants.