title: "Periodic fever" without fever: two cases of non-febrile TRAPS with mutations in the TNFRSF1A gene presenting with episodes of inflammation or monosymptomatic amyloidosis.
abstract: BACKGROUND
  Tumour necrosis factor (TNF) receptor associated periodic syndrome (TRAPS) is caused by dominant mutations in the TNFRSF1A gene. In typical cases TRAPS begins early in childhood and is characterised by high and remittent fever over a period of 1-4 weeks or longer, accompanied by systemic and local inflammation.
  
  
  METHODS
  Patient 1 presented with recurrent episodes of weakness, migrating myalgias, arthralgias, exanthema, and chest pain lasting for 1-4 weeks, but without any fever over an initial period of 4 years at least. Diagnosis of TRAPS was confirmed by the heterozygous mutation Y20H in TNFRSF1A. Patient 2, a 23 year old woman never had any symptoms indicative of TRAPS. Genetic evaluation of all members of her family with a TRAPS index patient disclosed the T50M mutation in TNFRSF1A. A medical check up showed proteinuria, and renal biopsy disclosed AA amyloidosis.
  
  
  CONCLUSIONS
  TRAPS associated mutations can induce considerable inflammation that is not necessarily accompanied by fever. Even monosymptomatic severe amyloidosis can occur in these patients. Genetic counselling and appropriate management to prevent or mitigate amyloidosis may be necessary.
authors.affiliation: Department of Paediatric Pulmonology and Immunology, Charité Campus Virchow-Klinikum, Universitaetsmedizin Berlin, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Kallinich
authors.forename: D
authors.initials: D
authors.lastname: Haffner
authors.forename: B
authors.initials: B
authors.lastname: Rudolph
authors.forename: R
authors.initials: R
authors.lastname: Schindler
authors.forename: S
authors.initials: S
authors.lastname: Canaan-Kühl
authors.forename: R
authors.initials: R
authors.lastname: Keitzer
authors.forename: G R
authors.initials: GR
authors.lastname: Burmester
authors.forename: A
authors.initials: A
authors.lastname: Roesen-Wolff
authors.forename: J
authors.initials: J
authors.lastname: Roesler
mesh_terms: D000328:Adult; D028226:Amyloidosis, Familial / Q000235:genetics*; D004252:DNA Mutational Analysis; D010505:Familial Mediterranean Fever / Q000235:genetics*; D005260:Female; D006801:Humans; D007249:Inflammation; D008297:Male; D009154:Mutation; D010375:Pedigree; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha
chemical_list: D047888:Receptors, Tumor Necrosis Factor, Type I; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha