RESUMEN
BACKGROUND: HFE-related genetic haemochromatosis (GH) is the commonest inherited genetic disorder in Caucasian populations with approximately one in 180 of individuals in the west of Scotland homozygous for the common C282Y mutation. The clinical diagnosis of GH, however, remains relatively uncommon - suggesting either under diagnosis or low clinical penetrance. AIM: We aimed to assess the biochemical and clinical penetrance of GH in first-degree relatives of patients with known GH, who subsequently themselves screened positive for the common GH mutations. METHODS: Individuals were identified from two large teaching hospitals in North Glasgow from July 1997 to July 2005 diagnosed with GH after predictive genetic testing after a relative was found to have GH. Details of patient history, biochemistry and known comorbidity at diagnosis and results of related further investigations were collected. RESULTS: Sixty-three individuals were identified, 31 (49%) of whom were males. Fifty-five individuals (87%) were C282Y homozygous and the remaining eight were compound heterozygotes for C282Y and H63D. All 31 male patients were found to have evidence of iron overload as opposed to 63% of females. Elevated liver enzyme levels were encountered in 15 patients (24%). All except one had evidence of iron overload. Four individuals underwent a liver biopsy, two of whom had hepatic fibrosis. Four patients were found to be diabetic. A full clinical history was obtained from 54 of 63 individuals, 38 (70%) of whom were entirely asymptomatic. Thirteen individuals complained of joint pains and a further nine complained of fatigue. CONCLUSION: This study suggests that although biochemical penetrance of GH is high, the clinical penetrance is low.
Asunto(s)
Pruebas Genéticas , Hemocromatosis/sangre , Penetrancia , Adulto , Anciano , Envejecimiento/sangre , Artralgia/etiología , Diabetes Mellitus Tipo 2/etiología , Fatiga/etiología , Femenino , Ferritinas/sangre , Hemocromatosis/complicaciones , Hemocromatosis/diagnóstico , Hemocromatosis/genética , Proteína de la Hemocromatosis , Heterocigoto , Antígenos de Histocompatibilidad Clase I/genética , Homocigoto , Humanos , Sobrecarga de Hierro/genética , Hígado/enzimología , Masculino , Proteínas de la Membrana/genética , Persona de Mediana Edad , Mutación , Transferrina/metabolismoRESUMEN
OBJECTIVES: The management of alcoholic hepatitis remains controversial. Anti-tumour necrosis factor treatments have been studied recently. We piloted the use of granulocytapheresis (GCAP) in the management of severe alcoholic hepatitis. METHODS: GCAP was performed on six patients with severe alcoholic hepatitis. Their clinical and laboratory progress was reviewed retrospectively. RESULTS: Six of the patients underwent at least one session of GCAP. Three of the patients had coexistent renal failure and five of the six patients were corticosteroid nonresponders. All patients tolerated the procedure. However, three of the patients died during their hospital admission within 4 days of GCAP treatment. These three patients suffered from torrential variceal haemorrhage, multiorgan failure and pneumonia, respectively. Two patients died 18 and 25 days after their GCAP treatment, both with multiorgan failure. The survivor was the sole corticosteroid responder of the group. There was a trend towards a fall in serum bilirubin level after GCAP, but this did not reach significance. CONCLUSION: GCAP is tolerated in severe alcoholic hepatitis; however, we have no evidence of survival advantage with this treatment.