RESUMEN
Hereditary haemochromatosis is an autosomal recessive disorder of iron regulation that results in abnormal intestinal iron absorption with progressive iron overloading of parenchymal cells. Two specific, single point mutations of the HFE gene (C282Y and H63D) have been described in haemochromatosis patients. Epidemiological studies have revealed a strict association between hereditary haemochromatosis and C282Y homozygosis or C282Y/H63D compound heterozygosis, suggesting that these mutations may provide a useful tool for diagnosis. However, recent investigations from southern Europe have reported lower allelic frequencies of the C282Y mutation among haemochromatosis patients, apparently depending on the geographical area of the population analysed. To assess the predictive value of the detection of the C282Y and H63D HFE mutations in our geographical area, we have evaluated their occurrence in 46 haemochromatosis patients from southern Italy. We found that only 19.6% of our patients were homozygous for the C282Y mutation and 21.7% were compound C282Y/H63D heterozygotes. Among the remaining 59%, approximately 40% did not display any of the known HFE mutations. We conclude that, in southern Italy, another genetic determinant/s must be responsible for many haemochromatosis cases and that a genetic screening for the C282Y and H63D HFE mutations is not sufficient for hereditary haemochromatosis diagnosis.
Asunto(s)
Hemocromatosis/epidemiología , Hemocromatosis/genética , Adulto , Anciano , Estudios de Casos y Controles , Cisteína/genética , Femenino , Frecuencia de los Genes , Hemocromatosis/patología , Proteína de la Hemocromatosis , Heterocigoto , Histidina/genética , Antígenos de Histocompatibilidad Clase I/genética , Homocigoto , Humanos , Italia/epidemiología , Masculino , Proteínas de la Membrana/genética , Persona de Mediana Edad , Mutación/genética , PrevalenciaRESUMEN
Spleen size was assessed in 73 patients with thrombocytosis and in 15 healthy subjects, comparing palpation with ultrasonography (US) measurement of longitudinal diameter and volume. Intraobserver and interobserver variability for volume on US, checked in 12 patients, was very low. Correlation between spleen volume measured by US and that measured by computed tomography was excellent. Splenomegaly was detected by palpation in 25% of patients, by US assessment of longitudinal diameter in 33%, and by US assessment of volume in 52%. After diagnostic work-up, 54 patients had a diagnosis of essential thrombocythemia (ET), 4 of idiopathic myelofibrosis (IMF), and 15 of secondary thrombocytosis (ST). Spleen volume in patients with ST was in the normal range (138 +/- 47 mL) and was significantly lower than that in patients with ET or IMF (370 +/- 210 mL; P <.001). Thus, US-measured volume was the most sensitive method for identifying nonpalpable splenomegaly in patients with primary myeloproliferative diseases, and it may help in distinguishing these diseases from reactive disorders.
