RESUMEN
BACKGROUND: The pathophysiology of hemophilic arthropathy is complex and not completely understood. In this study, we aimed to identify biomarkers that can affect the hemophilic arthropathy severity. METHODS: Fifty patients were analyzed for biomarker frequencies; in 37 patients, articular symptoms were evaluated based on the physical joint examination score, and in 18, it was based on magnetic resonance imaging. Eight polymorphisms, namely FV 1691G>A, FII 20210G>A, MTHFR 677C>T and 1298A>C, TNFα-308G>A and -238G>A, ACAN VNTR, and IL1RN*2-VNTR were identified. RESULTS: Patients with the MTHFR 677TT genotype showed a higher number of affected joints (1.83 ± 0.9 vs. 0.55 ± 0.7 for CC; p = .023), whereas those with the MTHFR 1298AC genotype exhibited higher effusion according to two radiologists (0.90 ± 0.31/1.20 ± 0.63 vs. 0.38 ± 0.52/0.50 ± 0.53 for AA genotype; p = .043/0.036, respectively). In addition, patients with the TNFα-308GA genotype had more subchondral cysts (0.75 ± 0.95 vs. 0.07 ± 0.26 for GG genotype; p = .041). CONCLUSIONS: The distribution of risk genotypes for MTHFR and TNFα-308GA suggests their association with clinical parameters of hemophilic arthropathy. Cohort studies are essential to verify these associations.
Asunto(s)
Cartílago/patología , Marcadores Genéticos , Hemartrosis/diagnóstico , Hemofilia A/fisiopatología , Inflamación/diagnóstico , Adolescente , Cartílago/metabolismo , Niño , Preescolar , Femenino , Hemartrosis/epidemiología , Hemartrosis/genética , Humanos , Incidencia , Lactante , Recién Nacido , Inflamación/epidemiología , Inflamación/genética , Masculino , México/epidemiología , PronósticoRESUMEN
Inherited factor X deficiency (FXD) is a rare (1:1,000,000) recessive bleeding disorder. The clinical and laboratory phenotypes of FXD are poorly correlated and few regional studies on the genotype and the clinical manifestations of FXD are known. To understand the association between clinical manifestations and causative genotype, detailed evaluation of bleeding pattern in a high number of patients is needed. This international study analysed the phenotype and genotype of 102 subjects from Central Europe (Germany, Poland and Slovakia) and Latin America (Costa Rica and Venezuela) with causative mutations in the F10 gene, via sequencing. Twenty-eight homozygous, seven compound-heterozygous and 67 heterozygous FXD subjects were characterized. Twenty-nine different causative mutations, including 15 novel mutations, were analysed. Spontaneous bleeding symptoms in 42 symptomatic individuals (26 homozygous, seven compound heterozygous and nine heterozygous) comprised easy bruising (55%), haematoma (43%), epistaxis (36%), haemarthrosis (33%), intracranial haemorrhage (ICH; 21%), and gastrointestinal (GI) haemorrhage (12%). The manifestation of bleeding symptoms in 9 of 67 (13%) symptomatic heterozygous subjects is described. The bleeding patterns of the enrolled patients showed differences that are associated with the types of F10 mutation, and the corresponding genotypes. The homozygous patients were evaluated for genotype-phenotype correlation. The results suggested that ICH seems to be associated with the F10 mutation Gly380Arg, and possibly with the mutations IVS7-1G>A and Tyr163delAT. A tentative association of other mutations to severe symptoms such as haemarthrosis and GI haemorrhage is reported. The severity of FXD, the genotype-phenotype association, and the results of regional studies are discussed.
Asunto(s)
Deficiencia del Factor X/genética , Adolescente , Adulto , Anciano , Niño , Preescolar , Costa Rica/epidemiología , Epistaxis/epidemiología , Epistaxis/genética , Europa (Continente)/epidemiología , Factor X/genética , Deficiencia del Factor X/congénito , Deficiencia del Factor X/epidemiología , Femenino , Hemartrosis/epidemiología , Hemartrosis/genética , Hematoma/epidemiología , Hematoma/genética , Hemorragia/epidemiología , Hemorragia/genética , Heterocigoto , Homocigoto , Humanos , Masculino , Persona de Mediana Edad , Mutación/genética , Fenotipo , Prevalencia , Venezuela/epidemiologíaRESUMEN
This study assesses chromosomal structural changes (CSCs) studied by conventional lymphocyte cultures and banding techniques in 79 hemophilic patients with hemarthrosis treated with radioactive synoviorthesis, 31 hemophilic patients with hemarthrosis not treated by this procedure, and 110 nonhemophilic patients matched by age and sex (control group). In 14 patients treated with 198Au (group A), premalignant CSCs and nonspecific CSCs were found, respectively, in 1.69% and 17.23% of metaphases. The former disappeared, but 1.7% of the nonspecific changes persisted 2 years after injection. In 31 patients treated with 186Rh (group B), CSCs were not found previous to radioactive synoviorthesis but were present as nonspecific changes in 1.25% of metaphases 6 months later; they disappeared 1 year after injection. In 34 patients treated with 90Y (group C), CSCs were not found previous to radioactive synoviorthesis but were present as nonspecific changes in 0.89% of metaphases 6 months later; they disappeared 1 year after injection. Only nonspecific CSCs were found in 0.79% of metaphases in patients not treated with radioactive synoviorthesis (group D). CSCs were not present in control subjects. The authors conclude that in some hemophilic patients with hemarthosis treated with radioactive synoviorthesis using 198Au, 186Rh, or 90Y, reversible premalignant or nonspecific CSCs could be present; nonspecific CSCs may persist in a low proportion of metaphases up to 2 years after injection when 198Au is used as the radioactive agent. Radioactive synoviorthesis seems to be from a cytogenetic point of view a safe alternative for these patients.