Two familial cases with tumor necrosis factor receptor-associated periodic syndrome caused by a non-cysteine mutation (T50M) in the TNFRSF1A gene associated with severe multiorganic amyloidosis.
An adolescent boy had had recurrent episodes of fever, abdominal pain, and arthralgias since the age of 7 years. Progressive renal failure due to renal amyloidosis developed, leading to renal transplant at the age of 14.5 years. Five years later, he developed AA amyloidosis in the transplant as well as the thyroid gland. His father had had similar symptoms including systemic amyloidosis since the age of 6 years. DNA sequence analysis revealed a heterozygous mutation in the TNFRSF1A (TNFa-receptor 1) gene (T50M) in both father and son causing tumor necrosis factor receptor-associated periodic syndrome (TRAPS). Previous phenotype/genotype analyses have proposed that this mutation is usually not associated with the occurrence of amyloidosis. This difference in the clinical course in different families may indicate a strong influence of modifier genes. Treatment with a TNFRSF1B fusion protein TNF antagonist (etanercept) favorably influenced the disease course.
Kallinich
Tilmann
T
Department of Pediatric Nephrology, Pulmonology and Immunology, Humboldt University, Berlin, Germany.
Briese
Sonia
S
Roesler
Joachim
J
Rudolph
Birgit
B
Sarioglu
Nanette
N
Blankenstein
Oliver
O
Keitzer
Rolf
R
Querfeld
Uwe
U
Haffner
Dieter
D
D000328:Adult; D028226:Amyloidosis, Familial / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D004252:DNA Mutational Analysis; D000068800:Etanercept; D010505:Familial Mediterranean Fever / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000188:drug therapy; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics* / Q000627:therapeutic use; D007676:Kidney Failure, Chronic / Q000175:diagnosis* / Q000503:physiopathology / Q000601:surgery; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D009154:Mutation; D010375:Pedigree; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics* / Q000627:therapeutic use; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics*; D018570:Risk Assessment; D012720:Severity of Illness Index; D016896:Treatment Outcome
D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D000068800:Etanercept