Unmasking amyloid light-chain amyloidosis through biochemical lens: diagnostic utility of urine immunofixation in serum-negative cases
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Lekha priyadharshini Kamarajan
Abstract
Objectives
AL amyloidosis is a rare disorder caused by deposition of misfolded immunoglobulin light chains as amyloid fibrils in vital body organs. The diagnosis requires a triad: identification of a monoclonal protein (via serum/urine studies), histological confirmation of amyloid deposits and clinical evidence of organ dysfunction. Serum protein electrophoresis (SPEP) and immunofixation (SIFE) are first-line tests but fail to detect monoclonal proteins in 10–20 % of cases, particularly those with low plasma cell burden or rapid renal excretion of FLCs. Serum free light chain (FLC) assays and urine immunofixation (UIFE) are indispensable in such scenarios but tissue biopsy remains the diagnostic cornerstone.
Case presentation
We discuss a 67-year-old man who presented with a 4-month history of progressive bilateral lower limb edema, fatigue and frothy urine. Initial evaluation revealed nephrotic-range proteinuria. SPEP and SIFE showed no monoclonal bands. X-ray skull revealed multiple punched-out lytic lesions, raising suspicion of an underlying plasma cell dyscrasia. UIFE identified a monoclonal lambda light chain. Renal biopsy confirmed amyloid deposition. The patient was initiated on bortezomib-dexamethasone chemotherapy, targeting the plasma cell clone to halt amyloid production.
Conclusions
This case underscores the diagnostic challenges of AL amyloidosis, particularly in serum-negative presentations with low tumor burden. Role of UIFE was pivotal in detecting monoclonal lambda light chains excreted via the kidneys, overcoming the limitations of serum-based assays. The absence of serum monoclonal proteins in early-stage disease mandates a multimodal approach: integrating clinical suspicion (e.g., nephrotic syndrome, cardiomyopathy, or neuropathy in older adults), urine studies, serum FLC assays, and targeted biopsies.
Acknowledgments
Patient, concerned relatives, hospital staff for their cooperation in this case.
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Research ethics: The Ethics Committee of the Institute, AIIMS Patna (IEC), waives Ethical Approval for case reports at our institute.
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Informed consent: Informed consent was obtained from all individuals included in this study, or their legal guardians or wards.
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Author contributions: LPK: collection of data, history and preparing first draft. MM: content, supervision, patient investigation, reviewing the first draft, editing, re-reviewing. SK: collection of data, supervison, reviewing final draft. AK: clinical workup, diagnosis, reviewing final draft. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Use of Large Language Models, AI and Machine Learning Tools: None declared.
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Conflict of interest: The authors state no conflict of interest.
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Research funding: None declared.
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Data availability: All relevant data have been submitted with the manuscript.
References
1. Reilly, JB, Myers, JS, Salvador, D, Trowbridge, RL. Use of a novel, modified fishbone diagram to analyze diagnostic errors. Diagnosis 2014;1:167–71. https://doi.org/10.1515/dx-2013-0040.Suche in Google Scholar PubMed
2. Palladini, G, Merlini, G, Obici, L, Milani, P, Foli, A, Lavatelli, F, et al.. Monoclonal gammopathy of undetermined significance (MGUS) and amyloidosis: a perspective. Blood 2012;120:1560–6. https://doi.org/10.1182/blood-2012-02-343021.Suche in Google Scholar
3. Dispenzieri, A, Gertz, MA, Kyle, RA, Larson, DR, Therneau, TM, Kumar, SK, et al.. The role of free light chains in diagnosis of AL amyloidosis. Semin Hematol 2015;52:52–8. https://doi.org/10.1053/j.seminhematol.2014.12.001.Suche in Google Scholar
4. Skinner, M, Sanchorawala, V, Seldin, DC, Quillen, K, Berk, JL, Dember, LM, et al.. Early diagnosis and treatment of AL amyloidosis. Nephrol Dial Transplant 2015;30:739–47. https://doi.org/10.1093/ndt/gfu479.Suche in Google Scholar
5. Buxbaum, JN, Ikeda, SI. Amyloidosis and the nervous system. Neurotherapeutics 2017;14:741–50. https://doi.org/10.1007/s13311-017-0545-1.Suche in Google Scholar
6. Gertz, MA, Lacy, MQ, Dispenzieri, A, Hayman, SR, Kumar, SK, Buadi, FK, et al.. AL amyloidosis: a disease of paraproteinemia. J Clin Oncol 2011;29:3445–52. https://doi.org/10.1200/JCO.2011.36.5419.Suche in Google Scholar
7. Linos, A, Shlipak, MG, Katz, R, Estrella, MM, Ix, JH, Rifkin, DE, et al.. Renal amyloidosis in elderly patients: diagnosis and management. Am J Kidney Dis 2017;70:505–12. https://doi.org/10.1053/j.ajkd.2017.04.006.Suche in Google Scholar PubMed
8. Sanchorawala, V, Skinner, M, Quillen, K, Berk, JL, Seldin, DC, Dember, LM, et al.. AL amyloidosis: diagnosis and treatment. Semin Hematol 2014;51:113–21. https://doi.org/10.1053/j.seminhematol.2014.01.002.Suche in Google Scholar
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