ABSTRACT
Juvenile hemochromatosis is a rare genetic disorder that causes iron overload. Clinical complications, which include liver cirrhosis, heart failure, hypogonadotropic hypogonadism and diabetes, appear earlier and are more severe than in HFE-related hemochromatosis. This disorder, therefore, requires an aggressive therapeutic approach to achieve iron depletion. We report here the case of a young Italian female with juvenile hemochromatosis who was unable to tolerate frequent phlebotomy because of coexistent ss-thalassemia trait. The patient was successfully iron-depleted by combining phlebotomy with recombinant human erythropoietin.
Subject(s)
Erythropoietin/therapeutic use , Hemochromatosis/complications , Hemosiderosis/therapy , Phlebotomy , beta-Thalassemia/complications , Adrenal Cortex Hormones/therapeutic use , Adrenal Insufficiency/drug therapy , Adrenal Insufficiency/etiology , Adult , Arrhythmias, Cardiac/etiology , Chelation Therapy/adverse effects , Chromosomes, Human, Pair 1/genetics , Deferoxamine/adverse effects , Deferoxamine/therapeutic use , Estrogen Replacement Therapy , Female , Hemochromatosis/classification , Hemochromatosis/genetics , Hemosiderosis/etiology , Hormone Replacement Therapy , Humans , Hypogonadism/drug therapy , Hypogonadism/etiology , Liver Cirrhosis/etiology , Phlebotomy/adverse effects , Progesterone/therapeutic use , Recombinant Proteins , beta-Thalassemia/drug therapy , beta-Thalassemia/genetics , beta-Thalassemia/therapyABSTRACT
BACKGROUND & AIMS: Patients with hemochromatosis show variable phenotype expression. We evaluated the frequency of hemochromatosis gene (HFE) mutations and the contribution of HFE genotype, ancestral haplotype, ethnic background, and additional factors (alcohol intake, hepatitis viruses, and beta-thalassemia trait) to the severity of iron overload in a large series of Italian patients with a hemochromatosis phenotype. METHODS: HFE genotype was studied in 188 patients. Phenotype evaluation was available in 153 men and 20 women and was based mainly on iron removed. HFE genotype was determined by a polymerase chain reaction restriction assay and ancestral haplotype through D6S265 and D6S105 microsatellite analysis. RESULTS: The frequency of C282Y homozygotes was 64%, with a decreasing gradient from north to south. C282Y homozygotes showed more severe iron overload than the other HFE genotypes. In the same group, ancestral haplotype was associated with a more severe phenotype. Additional factors may favor the development of a relatively mild hemochromatosis phenotype in patients nonhomozygous for the C282Y mutation. CONCLUSIONS: Hemochromatosis in Italy is a nonhomogenous disorder in which genetic and acquired factors are involved. In patients with a single or no HFE mutation, further studies will enable a differentiation between true genetic disorders and interactions between genetic and acquired factors.
Subject(s)
Genetic Variation , Hemochromatosis/genetics , Adult , Aged , Female , Gene Frequency , Genetic Variation/physiology , Genotype , Haplotypes/physiology , Humans , Italy , Male , Middle Aged , Mutation/genetics , PhenotypeABSTRACT
Juvenile Hemochromatosis (JH) is a rare genetic disorder that causes iron overload. JH clinical features are similar to those of hemochromatosis (HFE), but the clinical course is more severe and is characterized by an earlier onset and by a prevalence of cardiac symptoms and endocrine dysfunctions. Here we describe seven Italian patients belonging to five unrelated families with clinical features typical of JH. In four out of five families the parents were consanguineous. Analysis of HFE gene mutations in all the cases and nucleotide sequence of the gene in one case excluded this gene as responsible for JH. Segregation analysis of 6p markers closely associated with HFE in families with consanguineous parents clearly showed that JH is unlinked to 6p and thus genetically distinct from HFE.
Subject(s)
Hemochromatosis/genetics , Adolescent , Adult , Age Distribution , Child , Chromosomes, Human, Pair 6/genetics , Consanguinity , Female , Genetic Linkage , Haplotypes/genetics , Humans , Iron Overload/pathology , Italy , Lod Score , Male , PedigreeABSTRACT
A case of hepatic epithelioid haemangio-endothelioma is described in a 42-year-old female who presented with abdominal pain and hepatomegaly. The radiographic finding showed multiple hepatic lesions in both lobes. Diagnosis was based on the liver biopsy. The tumour cells were immunoreactive with factor VIII related antigen and vimentine. A liver transplantation was performed. Although at the time of diagnosis there was no clinical evidence of metastasis, the intra-operatorive examination revealed multiple mesenteric and pulmonary neoplastic nodules. The patient is alive and well seven months after liver transplantation.
Subject(s)
Hemangioendothelioma, Epithelioid/surgery , Liver Neoplasms/surgery , Liver Transplantation , Adult , Biopsy , Female , Hemangioendothelioma, Epithelioid/diagnosis , Hemangioendothelioma, Epithelioid/epidemiology , Hemangioendothelioma, Epithelioid/secondary , Humans , Liver/pathology , Liver Neoplasms/diagnosis , Liver Neoplasms/epidemiology , Lung Neoplasms/secondary , Mesentery , Peritoneal Neoplasms/secondaryABSTRACT
Des-gamma-carboxyprothrombin level was measured by enzyme immunoassay in the plasma of 39 patients suffering from hepatocellular carcinoma and 26 controls. Two of these were anticoagulated by warfarin and revealed very high positive values; the remaining 24, 8 healthy subjects and 16 patients with cirrhosis or chronic hepatitis, were negative. Values indicating pathology were found in 56.40% of patients suffering from hepatocellular carcinoma. All malignancies presenting diameter < or = 3 cm were negative, while high positive levels were found in patients with more advanced neoplasia. The alpha-fetoprotein was increased in 43.58% of the patients with hepatocellular carcinoma and in 6.25% of controls with chronic liver diseases. Positive values for both des-gamma-carboxyprothrombin and alpha- fetoprotein were detected in 12/39 patients. An increase of sensitivity (from 43.58 to 69.23%) in detecting hepatocellular carcinoma was found by the complementary use of the two markers relative to sole use of alpha-fetoprotein.
