Evaluation of E148Q and Concomitant AA Amyloidosis in Patients with Familial Mediterranean Fever
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Published on: June 9, 2018
Zehra Serap Arici1,2, Micol Romano3, David Piskin3,4,5
1Department of Paediatric Rheumatology, Sanliurfa Training and Research Hospital, Sanliurfa 63250, Turkey.
Abstract:
The aim of the study was to compare the clinical phenotype of patients with familial Mediterranean fever (FMF)-related AA amyloidosis, according to the age of FMF diagnosis and E148Q genotype. Patients with biopsy-confirmed FMF-related AA amyloidosis were included in the study. Tel-Hashomer criteria were applied in the diagnosis of FMF. All patients had detailed baseline assessment of clinical features, renal functions, genetic testing, histopathological diagnosis of amyloidosis, and treatment received. Multiple comparisons were performed according to the age of diagnosis, disease phenotype, mutation, and mortality. Our study included 169 patients with a diagnosis of AA amyloidosis. There were 101 patients diagnosed with FMF < 18 years of age and 68 patients diagnosed who were ≥18 years of age. The three most common clinical manifestations were fever (84.6%), abdominal pain (71.6%), and arthritis (66.9%). The most common allele among FMF patients was M694V (60.6%), followed by E148Q (21.4%), and M680I (10.3%). The most frequent genotypes were M694V/M694V (45.0%), M694V/E148Q (14.8%), and E148Q/E148Q (11.2%) among 169 patients in our cohort. During the follow-up period, 15 patients (10 male, 5 female) died, of whom 14 had M694V homozygous genotype and one was homozygous for E148Q. Clinicians should be aware of patients with homozygous E148Q genotype for close monitoring and further evaluation. The possible relationship between E148Q and AA amyloidosis needs to be confirmed in other ethnicities.
Insights
Familial Mediterranean Fever (FMF) patients with AA amyloidosis show varied clinical phenotypes. Homozygous E148Q genotype warrants close monitoring due to potential links with AA amyloidosis.
Area of Science:
- Genetics
- Internal Medicine
- Nephrology
Background:
- Familial Mediterranean Fever (FMF) is a genetic autoinflammatory disorder.
- AA amyloidosis is a serious complication of FMF, leading to organ damage.
- Understanding genotype-phenotype correlations is crucial for managing FMF-related AA amyloidosis.
Purpose of the Study:
- To compare clinical phenotypes of FMF-related AA amyloidosis based on age at diagnosis and E148Q genotype.
- To investigate the impact of specific genotypes, particularly E148Q, on disease presentation and outcomes.
- To identify risk factors for mortality in FMF-related AA amyloidosis.
Main Methods:
- Retrospective analysis of 169 patients with biopsy-confirmed FMF-related AA amyloidosis.
- Clinical features, renal function, genetic testing (including E148Q and M694V alleles), and histopathology were assessed.
- Comparisons were made based on age of FMF diagnosis, disease phenotype, genotype, and mortality.
Main Results:
- The most common symptoms were fever, abdominal pain, and arthritis.
- M694V was the most frequent allele, followed by E148Q.
- Homozygous E148Q genotype was observed in 11.2% of patients; one patient with this genotype died.
- Most deaths (14/15) occurred in patients with homozygous M694V genotype.
Conclusions:
- Clinicians should closely monitor patients with the homozygous E148Q genotype for FMF-related AA amyloidosis.
- Further research is needed to confirm the association between the E148Q genotype and AA amyloidosis across diverse ethnicities.
