Typing of hereditary renal amyloidosis presenting with isolated glomerular amyloid deposition

BACKGROUND: The commonly used methods for amyloid typing include immunofluorescence or immunohistochemistry (IHC), which sometimes may come with diagnostic pitfalls. Mass spectrometry (MS)-based proteomics has been recognized as a reliable technique in amyloid typing. CASE PRESENTATION: We reported two middle-aged patients who presented with proteinuria, hypertension and normal renal function, and both had a family history of renal diseases. The renal biopsies of both patients revealed renal amyloidosis with the similar pattern by massive exclusively glomerular amyloid deposition. The IHC was performed by using a panel of antibodies against the common types of systemic amyloidosis, and demonstrated co-deposition of fibrinogen Aα chain and apolipoprotein A-I in the glomerular amyloid deposits of each patient. Then the MS on amyloid deposits captured by laser microdissection (LMD/MS) and genetic study of gene mutations were investigated. The large spectra corresponding to ApoA-I in case 1, and fibrinogen Aα chain in case 2 were identified by LMD/MS respectively. Further analysis of genomic DNA mutations demonstrated a heterozygous mutation of p. Trp74Arg in ApoA-I in case 1, and a heterozygous mutation of p. Arg547GlyfsTer21 in fibrinogen Aα chain in case 2. CONCLUSIONS: The current study revealed that IHC was not reliable for accurate amyloid typing, and that MS-based proteomics and genetic analysis were essential for typing of hereditary amyloidosis.