ABSTRACT
OBJECTIVES: Muckle-Wells syndrome (MWS) and familial cold autoinflammatory syndrome (FCAS) are rare periodic fevers associated with CIAS1 mutations. A third entity, the chronic infantile neurological, cutaneous, articular (CINCA) syndrome was also recently associated with mutation in the same gene. A phenotypic and genotypic continuum seems to exist from the most benign (FCAS) to the most severe forms (CINCA). Although a CIAS1 mutation can be associated with two different phenotypes. METHODS: We report a family of three patients exhibiting the MWS and FCAS phenotypes. These phenotypes were associated with a novel missense mutation in CIAS1. RESULTS: Anakinra controlled inflammatory flares in the three patients. CONCLUSIONS: FCAS, MWS and CINCA could be different phenotype expressions of the same disease.
Subject(s)
Autoimmune Diseases/drug therapy , Autoimmune Diseases/genetics , Carrier Proteins/genetics , Genetic Predisposition to Disease , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Mutation, Missense , Adolescent , Adult , Arthralgia/genetics , Arthralgia/immunology , Autoimmune Diseases/physiopathology , Chronic Disease , Cold Temperature , Conjunctivitis/genetics , Conjunctivitis/immunology , DNA Mutational Analysis , Female , Fever/genetics , Fever/immunology , Follow-Up Studies , Heterozygote , Humans , Male , Middle Aged , NLR Family, Pyrin Domain-Containing 3 Protein , Pedigree , Phenotype , Risk Assessment , Severity of Illness Index , Syndrome , Treatment Outcome , Urticaria/genetics , Urticaria/immunologyABSTRACT
OBJECTIVE: The hyperimmunoglobulinaemia D and periodic fever syndrome (HIDS) was originally defined by the presence of a high serum level of immunoglobulin D associated with recurrent fever. Since the discovery of the mevalonate kinase gene (MVK) gene encoding the mevalonate kinase enzyme, most patients with a clinical diagnostic of HIDS are now found to have a mevalonate kinase deficiency based on metabolic and genetic data. We aimed to asses the value of a high IgD serum level for the diagnosis of HIDS in a cohort of patients with a phenotype of recurrent fever, and to characterize patients with a high IgD serum level without mevalonate kinase mutation. METHODS: Main clinical and biological data of 50 patients who presented with clinical signs compatible with HIDS have been prospectively registered on a standard form. Clinical data have been analysed according the IgD serum level and the presence of MVK mutation. RESULTS: The metabolic and genetic data establishing the diagnosis of HIDS correlated in all cases. In this series of 50 patients, the sensitivity of a high IgD value for the diagnosis of HIDS is 0.79. In five patients with MVK mutation, IgD levels were found to be in the normal range. Likelihood ratios indicate that IgD measurement is not relevant for the diagnostic of HIDS. Most patients with a high serum IgD level and no MVK mutation have no definite diagnosis. CONCLUSION: The clinical relevance of the IgD measurement for the diagnosis of MKD in our population appears as poor, as reflected by likelihood ratios which are both close to 1.
Subject(s)
Familial Mediterranean Fever/diagnosis , Immunoglobulin D/blood , Mevalonate Kinase Deficiency/diagnosis , Biomarkers/blood , Child , Child, Preschool , Familial Mediterranean Fever/genetics , Female , Humans , Male , Mevalonate Kinase Deficiency/genetics , Mutation , Phosphotransferases (Alcohol Group Acceptor)/deficiency , Phosphotransferases (Alcohol Group Acceptor)/genetics , Prospective Studies , Sensitivity and SpecificityABSTRACT
OBJECTIVE: Tumour necrosis factor receptor-associated periodic syndrome (TRAPS) has been associated with several mutations in the TNF receptor super family 1A (TNFRSF1A), including most cysteine substitutions. However, the nature of two substitutions, P46L and R92Q, remains a topic of discussion. The aim of this study was to assess the actual role of these two sequence variations in a series of patients with TRAPS. METHODS: The main clinical data of 89 patients with TRAPS have been prospectively registered on a standard form. 84 patients or members of families with recurrent episodes of inflammatory symptoms spanning a period of more than 6 months and harbouring a TNFRSF1A mutation were studied. Clinical data have been analysed according to the nature of the mutation-P46L, R92Q or others. RESULTS: P46L is often seen in patients from Maghreb and is associated with a mild phenotype. P46L appears as a polymorphism with a non-specific role in inflammation. R92Q is associated with a variable phenotype and presents as a low-penetrance mutation. Interpreting these results will require a comparison with clinical signs and genetic background.
