SUN-187 LYSOZYME AMYLOIDOSIS – TWO NOVEL CASES WITH NEWLY DESCRIBED GENETIC MUTATIONS

Abstract

Amyloidosis is a disorder of protein folding in which proteins are deposited as abnormal insoluble fibrils which disrupt tissue structures and cause disease. Lysozyme is a bacteriolytic enzyme present in secretions synthesised by gastrointestinal cells, macrophages and hepatocytes. Lysozyme amyloidosis is a rare form of hereditary amyloidosis which typically manifests with renal impairment, gastrointestinal symptoms and sicca syndrome. The natural history of lysozyme amyloidosis is felt to be indolent with slow progression of end organ damage associated with the condition. The complexity of diagnosing hereditary forms of amyloidosis likely results in underdiagnosis of the condition or inappropriate labeling of the condition as immunoglobulin associated amyloidosis. Measures utilised to identify immunoglobulin associated amyloidosis, such as serum or urinary protein measurements, are unable to utilised in identifying lysozyme amyloidosis with immunohistochemistry and molecular genetic testing being required for formal identification. We report two cases of patients with lysozyme amyloidosis managed by our service. Case 1 was referred to our service in May 2017. The 44-year-old woman was referred with chronic renal impairment and mild proteinuria (protein/creatinine ratio 22 mg/mmol) on a background of peptic ulcer disease managed with an oral proton pump inhibitor, chronic back pain, cigarette smoking, menorrhagia, dry eyes and bilateral knee osteoarthritis. Screening testing of serum free light chains, paraprotein, antinuclear antibody, complements and renal tract imaging were unremarkable. Renal biopsy identified heavy congo red deposits within glomerular, vascular and interstitial compartments. Transthyretin and amyloid A staining were negative. Further tissue assessment with mass spectrometry was performed identifying high levels of lysozyme consistent with lysozyme amyloidosis. Molecular genetic testing identified heterozygous presence for the c.176G>C variant in the LYZ gene, a variant of uncertain clinical significance. Case 2 was referred to our service in June 2018. The 43-year-old man presented with a creatinine of 251 with no background medical history. Screening testing of serum free light chains, paraprotein, antinuclear antibody, complements and renal tract imaging were unremarkable. Renal biopsy demonstrated diffuse congo red staining within glomerular, vascular and interstitial compartments. Transthyretin and amyloid A staining were negative. Molecular genetic testing identified presence for the c314A>T and c263C>A variant in the LYZ gene. Further testing of an affected parent confirmed the presence of the same LYZ genetic mutations. Lysozyme amyloidosis is a poorly characterised and rarely encountered hereditary form of amyloidosis. We report two cases of lysozyme amyloidosis encountered by our renal service with molecular genetic testing describing two novel genetic mutations. A high index of suspicion must be maintained to ensure appropriate classification of amyloidosis.