1963 - Clinical and Genetic Features of Autoinflammatory Syndromes in Hispanic Patients: The Chilean Experience

Tuesday, November 8, 2011: 9:00 AM-6:00 PM
Hall F2 - Poster Hall (McCormick Place West)
Cristian Vergara1, Arturo Borzutzky1, Miguel A. Gutierrez1, Sergio Iacobelli1, Eduardo Talesnik1, Maria Eugenia Martinez1, Lilith Stange1, Javier Basualdo2, Viviana Maluje3, Renato Jimenez4, Elena Jarpa5, Roberto Wiener6, Javier Tinoco6, Juan I. Arostegui7, Jordi Yague7 and Manuel Alvarez-Lobos1, 1Pontificia Universidad Catolica de Chile, Santiago, Chile, 2Universidad de Chile, Santiago, Chile, 3Hospital FACH, Santiago, Chile, 4Hospital Gustavo Fricke, Valparaiso, Chile, 5Hospital Naval Almirante Nef, Vina Del Mar, Chile, 6Hospital Militar, Santiago, Chile, 7Hospital Clínic / IDIBAPS, Barcelona, Spain
Presentation Number: 1963

Background/Purpose: Hereditary autoinflammatory syndromes (AIS) are rare genetic diseases characterized by recurrent episodes of inflammation. Little information is available concerning AIS in Latin American Hispanic population. The purpose of this study was to determine the clinical and genetic characteristics of AIS in Chilean population.

Method: A multicenter retrospective study of Hispanic patients from Chile with genetically-confirmed AIS was performed. Inclusion criteria for Familial Mediterranean Fever (FMF) were the presence of the characteristic clinical features associated with at least one mutated MEFV allele, whereas the TNF receptor-associated periodic syndrome (TRAPS) inclusion criteria were the presence of long inflammatory episodes associated with TNFRSF1A mutations. We included 13 patients, eight with FMF and five with TRAPS, evaluated at rheumatology or pediatric rheumatology clinics between January of 2007 and December of 2010. No patients with other AIS were seen in the study period. 

Result: All 13 patients were Chilean and had Hispanic Latin American ethnicity with no other known genetic backgrounds. Median age of onset of clinical symptoms was 8 years (range: 1-35) and 8 years (range: 0.3-21) for FMF and TRAPS, respectively. Median duration of fever was 3 days (range: 2.5 - 15) for FMF and 21 days (range: 9.5-30) for TRAPS. In FMF patients, fever was associated with abdominal pain (6/8), myalgias (5/8), arthritis (4/8), and rash (3/8). All FMF patients had at least partial response to colchicine therapy, with two patients fully resolving episodes of recurrent fevers. Reactive AA-type amyloidosis was not observed among this group of FMF patients. In TRAPS patients, febrile episodes were preceded by malaise and periorbital edema in two patients. During episodes symptoms accompanying fever were migratory myalgias (4/5), rash (3/5), arthralgias/arthritis (3/5), and abdominal pain (3/5). Two patients with TRAPS underwent surgery for acute abdomen. Fever episodes were responsive to high-dose corticosteroids in 4/5 patients with TRAPS. Genotyping of the MEFV gene in FMF patients revealed one patient with a homozygous M694V missense mutation, and heterozygous missense mutations in seven patients: M694V (n=3), E148Q, R717H, A744S, and A511V. Sequencing of the TNFRSF1A gene in TRAPS patients revealed heterozygous missense mutations in four patients: T50M, C30R, R92Q, and IVS3+30:G>A, and a 2-base pair deletion (IVS2-17_18del2bpCT) in one patient. Mutation in MEFV R717H and mutations in TNFRSF1A IVS2-17_18del2bpCT and IVS3+30:G>A are novel and have not been reported previously.

Conclusion: This study reports the largest series of genetically-confirmed AIS in Latin America, and adds evidence regarding the clinical and genetic characteristics of patients with FMF and TRAPS in Hispanic population. In this series, mutations identified in MEFV and TNFRSF1A genes include defects reported in other ethnicities and novel mutations.

Keywords: familial Mediterranean fever

Disclosure: C. Vergara, None; A. Borzutzky, None; M. A. Gutierrez, None; S. Iacobelli, None; E. Talesnik, None; M. E. Martinez, None; L. Stange, None; J. Basualdo, None; V. Maluje, None; R. Jimenez, None; E. Jarpa, None; R. Wiener, None; J. Tinoco, None; J. I. Arostegui, FIS PS09/01182 Grant, 2 ; J. Yague, FIS PS09/01182 Grant, 2 ; M. Alvarez-Lobos, FONDECYT Grant 1100971, 2 .