ABSTRACT
Introducción. Las inmunodeficiencias primarias son un grupo de enfermedades de origen genético que implican altera - ciones asociadas a la respuesta inmunológica. El infra diagnóstico de estas conlleva al retraso de tratamiento, evitables en gran parte; Entre estas existe el síndrome de Wiskott-Aldrich; es un trastorno raro, ligado al cromosoma X, recesivo, que se caracteriza por trom - bocitopenia, eczema e inmunodeficiencia donde su tratamiento curativo es el trasplante de medula ósea. CASO CLÍNICO : Paciente de 10 años, con antecedentes de múltiples hospitalizaciones por procesos infecciosos importantes: neumonías recurrentes, menin - gitis, diarreas, erupción cutánea generalizada y trombocitopenia de hasta 9,000 mm³. Después de múltiples estudios realizados, se confirma el diagnóstico de síndrome de Wiskott -Aldrich por inmunogenetica (mutación del gen WAS) y mediante colaboración médica internacional, se realiza trasplante de médula ósea con posterior resolución de su enfermedad. DISCUSION: Las inmunodeficiencias primarias son patologías más comunes de lo que se creía (prevalencia de hasta 1/1200), la evidencia de aparición y su importancia clínica deben ser tomadas en consideración. En este caso de Síndrome de Wiskot-Aldrich en donde el diagnóstico definitivo es in - munogenetico, (actualmente el país no cuenta), además de tratamiento inmuno-oncológico adecuado, el paciente pudo sobrevivir y mejorar su calidad de vida gracias a soporte investigativo y terapéutico multinacional. Existen colaboraciones multicentricas como el consorcio de tratamiento inmunodeficiencias primarias, que tienen como objetivo colaborar activamente en el diagnóstico y tratamien - to estos casos, salvaguardando la vida de estos pacientes y ayudando a comprender estas enfermedades raras...(AU)
Subject(s)
Humans , Autoimmune Diseases , Bone Marrow Transplantation/methods , Thrombocytopenia/complications , Wiskott-Aldrich Syndrome/diagnosis , X ChromosomeABSTRACT
Hereditary periodic fever syndromes (HPFS) are rare genetic diseases characterized by recurrent episodes of inflammation. Little information is available concerning HPFS in Latin American Hispanic population. The purpose of this study was to determine the clinical and genetic features of HPFS in Chilean population. A multicenter retrospective study of Hispanic Chilean patients with genetically confirmed HPFS was performed. We included 13 patients, 8 with familial Mediterranean fever (FMF) and 5 with TNF receptor-associated periodic syndrome (TRAPS), evaluated at rheumatology or pediatric rheumatology clinics between January 2007 and December 2010. Median age of symptoms onset 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. Genotyping of the MEFV gene in FMF patients revealed a homozygous M694V missense mutation in one patient, 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:GâA, and a two-base pair deletion (IVS2-17_18del2bpCT) in one patient. Mutation in MEFV R717H and mutations in TNFRSF1A IVS2-17_18del2bpCT and IVS3+30:GâA are novel and have not been described previously. This study reports the largest series of genetically confirmed HPFS in Latin America, and adds evidence regarding the clinical and genetic characteristics of patients with FMF and TRAPS in Hispanic population. Mutations identified in MEFV and TNFRSF1A genes include defects reported in other ethnicities and novel mutations.
Subject(s)
Cytoskeletal Proteins/genetics , Familial Mediterranean Fever , Genetic Predisposition to Disease , Mutation, Missense , Receptors, Tumor Necrosis Factor, Type I/genetics , Adolescent , Adult , Child , Child, Preschool , Chile/epidemiology , DNA Mutational Analysis , Familial Mediterranean Fever/epidemiology , Familial Mediterranean Fever/genetics , Familial Mediterranean Fever/pathology , Female , Humans , Infant , Male , Pyrin , Recurrence , Retrospective Studies , Young AdultABSTRACT
It has been suggested that the R92Q mutation of the tumour necrosis factor receptor superfamily 1A (TNFRS1A) gene may be implicated in different inflammatory disorders. The aim of this study was to establish the role of this mutation as a determinant of Crohn`s disease (CD) susceptibility and/or clinical phenotype. One hundred and sixty-five CD patients and 203 healthy controls were prospectively included. The frequency of individuals carrying the R92Q mutation was similar between CD patients (4.24 percent) and controls (4.43 percent) (OR: 0.95; 95 percent CI = 0.34-2.62). In the genotype-phenotype evaluation, the univariate analysis showed that extra-intestinal manifestations were positively associated with the presence of R92Q mutation (p = 0.025; OR: 5.56; 95 percent CI = 1.04-29.6). In the multivariate analysis, presence of R92Q mutation was independently associated to extra-intestinal manifestations of CD, specially cutaneous manifestations (p = 0.02; OR: 5.17, 95 percent CI = 1.07-24.8). The R92Q mutation of TNFRSF1A gene is not a determinant of CD susceptibility, but contributes to the appearance of extra-intestinal manifestations of the disease.
Se ha sugerido que la mutación R92Q del gen de la super-familia del receptor del factor de necrosis tumoral 1A (TNFRS1A) podría estar relacionada con diversos trastornos inflamatorios. El objetivo de este estudio fue determinar el papel de esta mutación como factor determinante de la susceptibilidad y/o fenotipo clínico de la enfermedad de Crohn (EC). Ciento sesenta y cinco pacientes con EC y 203 controles sanos fueron incluidos de manera prospectiva. La frecuencia de individuos portadores de la mutación R92Q fue similar entre los pacientes con EC (4,24 por ciento) y los controles (4,43 por ciento) (OR: 0,95; 95 por ciento IC = 0,34-2,62). En la evaluación genotipo-fenotipo, el análisis univariado indicó que las manifestaciones extra-intestinales estaban relacionadas con la presencia de la mutación R92Q (p = 0,025; OR: 5,56; 95 por ciento IC = 1,04-29,6). En el análisis multivariado, la presencia de la mutación R92Q estuvo relacionada de manera independiente con las manifestaciones extra-intestinales de la EC, especialmente manifestaciones cutáneas (p = 0,02; OR: 5,17, 95 por ciento IC = 1,07-24,8). La mutación R92Q del gen TNFRSF1A no es un factor determinante de susceptibilidad a EC, pero contribuye a la aparición de manifestaciones extra-intestinales de la enfermedad.
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Crohn Disease/complications , Crohn Disease/genetics , Receptors, Tumor Necrosis Factor, Type I/genetics , Inflammatory Bowel Diseases/genetics , Skin Diseases/etiology , Case-Control Studies , Follow-Up Studies , Phenotype , Genotype , MutationABSTRACT
Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPS) is an autoinflammatory disorder associated to a mutation of the Tumor Necrosis Factor Receptor 1 (TNFR1) whose clinical presentation consists on recurrent episodes of prolonged fever, abdominal pain, myalgias, migratory cutaneous erythema, conjunctivitis or periorbitary edema. The diagnosis is confirmed by genetic analysis of the TNFR1 gene. Its main complication is amyloidosis and the treatment is based on the use of corticosteroids or anti-TNF antibodies. We report a 17 year-old male and 23 year-old female with the syndrome. Both cases had heterozygous mutations of the TNFR1 gene, C30R in the first case and T50M in the second case.
Subject(s)
Adolescent , Adult , Female , Humans , Male , Familial Mediterranean Fever/genetics , Mutation/genetics , Receptors, Tumor Necrosis Factor, Type I/genetics , Familial Mediterranean Fever/drug therapy , Familial Mediterranean Fever/pathology , Haplotypes/genetics , SyndromeABSTRACT
Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPS) is an autoinflammatory disorder associated to a mutation of the Tumor Necrosis Factor Receptor 1 (TNFR1) whose clinical presentation consists on recurrent episodes of prolonged fever, abdominal pain, myalgias, migratory cutaneous erythema, conjunctivitis or periorbitary edema. The diagnosis is confirmed by genetic analysis of the TNFR1 gene. Its main complication is amyloidosis and the treatment is based on the use of corticosteroids or anti-TNF antibodies. We report a 17 year-old male and 23 year-old female with the syndrome. Both cases had heterozygous mutations of the TNFR1 gene, C30R in the first case and T50M in the second case.