Familial Mediterranean fever, inflammation and nephrotic syndrome: fibrillary glomerulopathy and the M680I missense mutation.
BACKGROUND
Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by inflammatory serositis (fever, peritonitis, synovitis and pleuritis). The gene locus responsible for FMF was identified in 1992 and localized to the short arm of chromosome 16. In 1997, a specific FMF gene locus, MEFV, was discovered to encode for a protein, pyrin that mediates inflammation. To date, more than forty missense mutations are known to exist. The diversity of mutations identified has provided insight into the variability of clinical presentation and disease progression.


METHODS
We report an individual heterozygous for the M680I gene mutation with a clinical diagnosis of FMF using the Tel-Hashomer criteria. Subsequently, the patient developed nephrotic syndrome with biopsy-confirmed fibrillary glomerulonephritis (FGN). Further diagnostic studies were unremarkable with clinical workup negative for amyloidosis or other secondary causes of nephrotic syndrome.


CONCLUSIONS
Individuals with FMF are at greater risk for developing nephrotic syndrome. The most serious etiology is amyloidosis (AA variant) with renal involvement, ultimately progressing to end-stage renal disease. Other known renal diseases in the FMF population include IgA nephropathy, IgM nephropathy, Henoch-Schönlein purpura as well as polyarteritis nodosa.


CONCLUSIONS
To our knowledge, this is the first association between FMF and the M680I mutation later complicated by nephrotic syndrome and fibrillary glomerulonephritis.
Fisher
Patrick W
PW
Department of Medicine, Northwestern University Feinberg School of Medicine, Evanston Northwestern Healthcare, Evanston, IL, USA. pfisher002@md.northwestern.edu
Ho
L Tammy
LT
Goldschmidt
Robert
R
Semerdjian
Ronald J
RJ
Rutecki
Gregory W
GW
D010505:Familial Mediterranean Fever / Q000150:complications* / Q000235:genetics*; D005921:Glomerulonephritis / Q000150:complications* / Q000235:genetics*; D006801:Humans; D007249:Inflammation; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D009404:Nephrotic Syndrome / Q000150:complications* / Q000235:genetics*