Concurrent fabry disease and monoclonal gammopathy of renal significance: a case report.

BACKGROUND

Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by genetic variant in the GLA gene, resulting in reduced α-galactosidase A (α-Gal A) activity and accumulation of glycosphingolipid substrates in multiple organs. Monoclonal gammopathy of renal significance (MGRS) refers to a group of disorders where monoclonal immunoglobulins produced by low-tumor-burden B-cell or plasma cell clones induce renal injury. There have never been any reports of FD and MGRS coexisting.

CASE PRESENTATION: A 69-year-old male patient was hospitalized several times due to episodes of heart failure. His left ventricular enlargement had long been misdiagnosed as hypertrophic cardiomyopathy. One year after the initial heart failure episode, his renal function declined. Serum immunofixation electrophoresis detected IgG-λ monoclonal immunoglobulin, and renal biopsy confirmed proliferative glomerulonephritis with monoclonal immunoglobulin deposition (PGNMID). Further genetic testing revealed a heterozygous pathogenic genetic variant in the GLA gene (c.640-801G > A) and elevated Lyso-Gb3 levels, confirming the diagnosis of FD complicated by MGRS (PGNMID, IgG1-λ type). The patient's cardiac and renal functions have remained stable following enzyme replacement therapy and targeted clonal therapy.

CONCLUSION

Clinically, patients who exhibit unexplained left ventricular hypertrophy together with renal impairment and monoclonal immunoglobulin deposition should be evaluated for the potential comorbidity of rare diseases. For the diagnosis of such complicated co-morbid disorders, renal biopsies and genetic testing are essential.