Fibrinogen A Alpha-Chain Amyloidosis in Two Chinese Patients

Zhen-Yu Li; Shuang Wang; Dan-Yang Li; Dan Liu; Su-Xia Wang; Xiao-Juan Yu; Gang Liu; Fu-De Zhou; Ming-Hui Zhao

doi:10.3389/fmed.2022.869409

Fibrinogen A Alpha-Chain Amyloidosis in Two Chinese Patients

Front Med (Lausanne). 2022 Apr 28:9:869409. doi: 10.3389/fmed.2022.869409. eCollection 2022.

Authors

Zhen-Yu Li^{1

2

3

4

5}, Shuang Wang^{1

2

3

4

5}, Dan-Yang Li^{1

2

3

4

5}, Dan Liu⁶, Su-Xia Wang^{1

2

3

4

5}, Xiao-Juan Yu^{2

3

4

5}, Gang Liu^{2

3

4

5}, Fu-De Zhou^{2

3

4

5}, Ming-Hui Zhao^{2

3

4

5}

Affiliations

¹ Laboratory of Electron Microscopy, Pathological Center, Peking University First Hospital, Beijing, China.
² Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.
³ Renal Pathological Center, Institute of Nephrology, Peking University, Beijing, China.
⁴ Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China.
⁵ Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Beijing, China.
⁶ Proteomics Laboratory, Medical and Healthy Analytical Center, Peking University Health Science Center, Beijing, China.

Abstract

Objectives: 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.

Methods: 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.

Results: 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.

Conclusions: We reported two AFib amyloidosis patients in China, one of them coexisted with ALECT2 amyloidosis simultaneously.

Keywords: China; LECT2; amyloidosis; fibrinogen; gene mutation; kidney; mass spectrometry.

Publication types

Case Reports