Apolipoprotein C-II Deposition Amyloidosis: A Potential Misdiagnosis as Light Chain Amyloidosis

Abstract

Hereditary amyloidoses are rare and pose a diagnostic challenge. We report a case of hereditary amyloidosis associated with apolipoprotein C-II deposition in a 61-year-old female presenting with renal failure and nephrotic syndrome misdiagnosed as light chain amyloidosis. Renal biopsy was consistent with amyloidosis on microscopy; however, immunofluorescence was inconclusive for the type of amyloid protein. Monoclonal gammopathy evaluation revealed kappa light chain. Bone marrow biopsy revealed minimal involvement with amyloidosis with kappa monotypic plasma cells on flow cytometry. She was started on chemotherapy for light chain amyloidosis. She was referred to the Mayo clinic where laser microdissection and liquid chromatography mass spectrometry detected high levels of apolipoprotein C-II, making a definitive diagnosis. Apolipoprotein C-II is a component of very low-density lipoprotein and aggregates in lipid-free conditions to form amyloid fibrils. The identification of apolipoprotein C-II as the cause of amyloidosis cannot be solely made with routine microscopy or immunofluorescence. Further evaluation of biopsy specimens with laser microdissection and mass spectrometry and DNA sequencing of exons should be done routinely in patients with amyloidoses for definitive diagnosis. Our case highlights the importance of determining the subtype of amyloidosis that is critical for avoiding unnecessary therapy such as chemotherapy.

Amyloid Typing by Mass Spectrometry in Clinical Practice: a Comprehensive Review of 16,175 Samples

“…Nonetheless, when coupled with a robust quality control and quality assurance system 25 and advanced bioinformatics, 31,36 it can be applied to routine reference laboratory practice as shown in this study and in other published studies. 32,[37][38][39][40][41][42][43] In this study of routine clinical samples sent for amyloid typing to our reference laboratory, we identified 21 different amyloid types. These amyloid proteins represent the entire spectrum of common and rare amyloidrelated diseases, including hereditary (mutated ATTR, AFib, AApoAI, AApoCII, AGel, and ALys), neoplastic (AL, APro, and ACal), chronic inflammatory (AA and ALect2), iatrogenic (AIns and AEnf), and age-related (ATTRwt) diseases.…”

N- and C-terminal regions of αB-crystallin and Hsp27 mediate inhibition of amyloid nucleation, fibril binding, and fibril disaggregation

“…Very lowdensity lipoprotein-bound apoC-II is comprised of amphipathic a helices (21); however, lipid-free apoC-II is unstable and prone to aggregation. Amyloid formation by apoC-II in vitro is well-characterized (22)(23)(24), and mutations in apoC-II cause renal amyloidosis (25,26). The biological roles of a-syn are not well-understood; however, it is highly expressed in multiple regions of the brain and is thought to play a role in vesicular trafficking and neurotransmitter release (27).…”