Type 3 hemochromatosis and beta-thalassemia trait.
Type 3 hemochromatosis is a rare autosomal recessive disorder due to mutations of the TFR2 gene. We describe clinical, biochemical and histopathologic findings of a patient with type 3 hemochromatosis at presentation and during a follow-up of more than 20 yr and we evaluate the effect of an associated beta-thalassemia trait on phenotypic expression. At the age of 33 yr the patient showed a marked iron overload and severe iron-related complications. After removal of 26 g of iron by subcutaneous deferoxamine infusion a marked clinical improvement was observed. Liver biopsies, performed at the age of 34 and 49 yr, indicate that in type 3 hemochromatosis there is a progressive hepatocellular iron accumulation from Rappaport's zone 1-3 and that iron loading in sinusoidal and portal macrophages occurs only in the more advanced stage. As observed in HFE hemochromatosis, the beta-thalassemia trait seems to aggravate the clinical picture of patients lacking TFR2, favoring higher rates of iron accumulation probably by activation of the erythroid iron regulator.
Riva
Alessia
A
Clinica Medica, Azienda Ospedaliera San Gerardo, Università Milano-Bicocca, Via Donizetti 106, 20052 Monza, Italy.
Mariani
Raffaella
R
Bovo
Giorgio
G
Pelucchi
Sara
S
Arosio
Cristina
C
Salvioni
Alessandra
A
Vergani
Anna
A
Piperno
Alberto
A
D000328:Adult; D019943:Amino Acid Substitution; D001706:Biopsy; D002311:Cardiomyopathy, Dilated / Q000209:etiology; D015913:Chelation Therapy; D004252:DNA Mutational Analysis; D003676:Deferoxamine / Q000627:therapeutic use; D018450:Disease Progression; D005091:Exons / Q000235:genetics; D006432:Hemochromatosis / Q000150:complications / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007502:Iron Chelating Agents / Q000627:therapeutic use; D019190:Iron Overload / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000209:etiology; D008297:Male; D020125:Mutation, Missense; D011990:Receptors, Transferrin / Q000172:deficiency / Q000235:genetics; D017086:beta-Thalassemia / Q000150:complications / Q000235:genetics* / Q000473:pathology
D007502:Iron Chelating Agents; D011990:Receptors, Transferrin; C503640:TFR2 protein, human; D003676:Deferoxamine