Abstract: SA-PO0183
Homozygous Variant of Familial Mediterranean Fever, MEFV E148Q, Contributing to Amyloidosis in an Afebrile Japanese Patient
Session Information
- Tubular, Metabolic, and Systemic Noncystic Genetic Kidney Diseases
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1202 Genetic Diseases of the Kidneys: Non-Cystic (Complex and Non-Cystic Monogenic)
Authors
- Hayashi, Jeffrey W., University of Hawai'i at Manoa John A Burns School of Medicine, Honolulu, Hawaii, United States
- Izutsu, Christie H., University of Hawai'i at Manoa John A Burns School of Medicine, Honolulu, Hawaii, United States
- Kim, Lisa, University of Hawai'i at Manoa John A Burns School of Medicine, Honolulu, Hawaii, United States
Introduction
Renal dysfunction in Familial Mediterranean Fever (FMF) is uncommonly described as a presenting symptom despite its association with secondary amyloid (AA) deposition which is a major cause of mortality in chronic FMF. Although there are over 370 variants in pyrin, the 781 amino acid transcript of MEFV and the gene associated with FMF on chromosome 16, one of the five most common variants, E148Q has not been well characterized in patients with origins outside of Mesopotamia.
Case Description
We report an unusual case of a 63 year old ethnic Japanese patient who had unexplained proteinuria of up to 6.9 grams/24 hours with normal eGFR and serum creatinine of 0.6 mg/dL. A renal biopsy was non-diagnostic and bone marrow biopsy demonstrated a minute lambda restricted population of plasma cells (0.5% of all cells) with 13q deletion. Daratumumab-hyaluronidase was commenced but the patient continued to have proteinuria maximally up to 9.3 grams/24hr. Subsequent bone marrow biopsies showed no clonal plasma cells. A second renal biopsy 10 months later confirmed presence of 5.8 nm fibrils on electron microscopy. Renasight™ results showed no known pathogenic variants, however, variants of uncertain significance included a homozygous variant in MEFV corresponding to E148Q (p.Glu148Gln) .
Discussion
This is the first case of MEFV variant E148Q with biopsy proven amyloidosis in a patient with Japanese ancestry, highlighting the utility of exome sequencing in considering unique pathways of amyloidogenesis including pyrin mutations driving secondary amyloid deposition rather than paraproteinemia. Variants of uncertain significance should be considered for personalized diagnosis and treatment.
Normal light microscopy. Electron microscopy shows 5.8 nm fibrils.