ABSTRACT
RESUMEN La hemocromatosis hereditaria es una enfermedad metabólica infrecuente que afecta primariamente al hígado, y que se caracteriza por un incremento de la absorción intestinal de hierro. Se presentó un paciente de 49 años de edad, evaluado en consulta externa, desde alrededor de dos años atrás, por: astenia, anorexia, artralgias e hiperpigmentación cutánea, asociada a hipertransaminasemia y seronegatividad para virus B y C. Los niveles de saturación de transferrina y ferritina evidenciaron la sobrecarga de hierro, y el estado homocigoto para la mutación C282Y confirmó la sospecha diagnóstica; se descartaron otras condiciones como: hepatitis crónica por virus B y C, esteatohepatitis no alcohólica, anemia hemolítica crónica, anemia sideroblástica, talasemia mayor, u otras enfermedades metabólicas que afectan al hígado. La biopsia hepática mostró hallazgos típicos de esta condición. Las flebotomías semanales fueron bien toleradas y se logró una mejoría clínica del paciente y de los parámetros de laboratorio.
ABSTRACT Hereditary hemochromatosis is an uncommon metabolic disease, primarily affecting the liver in which increased intestinal absorption of iron is seen. We presented a 49- year -old patient who was evaluated in an outpatient clinic for suffering from asthenia, anorexia, arthralgia and skin hyperpigmentation associated with hypertransaminasemia and negative serology for B and C viruses from about two years ago. Serum ferritin, and transferrin saturation levels evidenced iron overload and homozygosity for the C282Y mutation confirmed the suspected diagnosis; other conditions were ruled out such as chronic hepatitis due to B and C viruses, non-alcoholic steatohepatitis, chronic hemolytic anemia, sideroblastic anemia, thalassemia major or some other metabolic diseases affecting the liver. Liver biopsy showed typical findings related to this condition. Weekly phlebotomies were well tolerated, as well as clinical improvement of the patient and laboratory parameters were achieved.
Subject(s)
Iron Overload , HemochromatosisABSTRACT
Aims: Porphyria Cutanea Tarda (PCT), the most common of porphyrias is triggered by several factors, including iron overload. Type I Hereditary Hemochromatosis is inherited as an autosomal recessive trait of the mutation p.C282Y or as a compound heterozygous form p.C282Y/p.H63D in HFE gene. Our aim was to study the frequency of HFE mutations in Argentinean PCT patients and in control subjects. Place and Duration of Study: CIPYP, CONICET, Hospital de Clínicas José de San Martín: Av. Córdoba 2351, 1º subsuelo, Buenos Aires, Argentina (1120). Between March 2008 and March 2010. Methodology: We analyzed HFE mutations in 103 PCT patients (67 males, 36 females) and in 93 control subjects (63 males and 30 females). PCT patients were classified as familial, sporadic or Type III PCT measuring URO-D activity in red blood cells. HFE mutations were detected by amplification and automatic sequencing of exons 2 and 4 in the HFE gene. In some cases p.H63D and p.C282Y mutations were also detected by digestion with restriction enzymes (Mbo I for p.H63D and Rsa I for p.C282Y), followed by 3% polyacrilamide gel electrophoresis. Results: In PCT group, 34.9% carried mutation p.H63D (26.2% heterozygous, 5.8% homozygous and 2.9% as p.C282Y/p.H63D) and 7.8% carried mutation p.C282Y (2.9% in heterozygocity, 1.9% in homozygocity and 2.9% as p.C282Y/p.H63D). In the control group, 30.1% carried p.H63D (28% in heterozygous and 2.1% in homozygous), and 5.4% had p.C282Y in heterozygosity. There were no significant differences between sporadic and familial PCT and neither between PCT and control groups. Our findings are in agreement with the prevalence of the Mediterranean origin of our patients, where p.C282Y mutation is less common than p.H63D mutation. Conclusion: We conclude that mutations in HFE gene do not play a relevant role in the triggering of PCT in our country.
ABSTRACT
La hemocromatosis hereditaria es un trastorno genético. En los últimos años se ha profundizado en el conocimiento de su fisiopatología y diagnóstico. Estos síndromes se caracterizan por sobrecarga de hierro y se distinguen varios subtipos de acuerdo con la mutación existente. Dentro de ellas, las mutaciones en el gen HFE o hemocromatosis hereditaria tipo I es la más común. Esta enfermedad tiene una gran morbilidad y mortalidad asociada a la sobrecarga del mineral. Se presentan 4 pacientes en los que por primera vez en Cuba se identificaron las mutaciones del gen HFE
Hereditary hemochromatosis is a genetic disorder. Detailed studies on its physiopathology and diagnosis have been carried out over the last years. The syndromes are characterized by iron overload and several subtypes are distinguished according to the existing mutation. Among them, the mutations in HFE gene or hereditary hemochromatosis type I is the most common. This disease has a great morbidity and mortality associated to mineral overload. For the first time in Cuba, we report four patients with confirmed mutations in HFE genes