[The H63D mutation in the HFE gene is related to the risk of hepatocellular carcinoma]. / La mutacion H63D del gen HFE se asocia con un riesgo aumentado de carcinoma hepatocelular .

AIM: To disclose whether mutations in the HFE gene inducing liver iron overload are related to the risk of hepatocellular carcinoma (HCC) in otherwise predisposed patients. PATIENTS AND METHODS: One hundred and ninety-six patients (161 males) diagnosed with HCC and 181 healthy controls were included in the study. All subjects were white Spaniards.C282Y and H63D mutations in the HFE gene were identified in leucocyte genomic DNA using a polymerase chain reaction (PCR) and specific restriction enzymes. RESULTS (CASES/CONTROLS): 1. Genotype distribution: a) C282Y mutation: homozygotes 1/0, heterozygotes 12/23, wild type 183/158 (p = 0.07, non significant); b) H63D mutation: homozygotes 9/5, heterozygotes 85/52, wild type 102/124 (0dds ratio 2.00, 95% C.I. 1.29-3.12, p = 0.002. Four cases and 6 controls were carriers of heterozygous mixed genotypes. 2. Allele frequencies: a) C282Y mutation: wild type allele 378/339, mutated allele 14/23 (p = 0.11, non significant); b) H63D mutation: wild type allele 289/300, mutated allele 103/62 (0dds ratio 1.72, 95% C.I. 1.19-2.50, p = 0.004). Age at diagnosis, gender and etiology of the underlying liver disease do not influence these findings. CONCLUSION: The C282Y mutation in the HFE gene is not related to the risk of HCC in non-hemochromatosis patients. The H63D mutation is associated with a higher risk of HCC in cirrhotic patients irrespective of their underlying liver disease.

La mutacion H63D del gen HFE se asocia con un riesgo aumentado de carcinoma hepatocelular / The H63D mutation of the HFE gene is related to the risk of hepatocellular carcinoma

Objetivo: comprobar si las mutaciones del gen HFE, que puedeninducir sobrecarga hepática de hierro, guardan relación conel riesgo de desarrollar carcinoma hepatocelular (CHC) en sujetospredispuestos a sufrir este tumor.Material y métodos: se han incluido 196 pacientes (161 varones)diagnosticados de CHC. Ninguno estaba diagnosticado dehemocromatosis. El grupo control estaba constituido por 181 sujetossanos. Todos los sujetos eran españoles de raza blanca.Las mutaciones C282Y y H63D del gen HFE se identificaronmediante reacción en cadena de polimerasa (PCR) sobre ADN genómicoleucocitario utilizando enzimas de restricción específicas.Resultados (casos/controles): 1. Distribución genotípica:a) mutación C282Y: 1/0 homocigotos, 12/23 heterocigotos,183/158 normales (p = 0,07, n.s.); y b) mutación H63D: 9/5homocigotos, 85/52 heterocigotos, 102/124 normales (odds ratio2,00, IC95% 1,29-3,12, p = 0,002). Cuatro casos y seis controleseran heterocigotos compuestos. 2. Frecuencias alélicas: a)mutación C282Y: normales 378/339, mutados 14/23 (p =0,11, n.s.); b) mutación H63D: normales 289/300; mutados103/62 (odds ratio 1,72, IC95% 1,19-2,50, p = 0,004). No seobservaron diferencias en relación con el sexo, la edad o la etiología(VHC, VHB, etílica o mixta) de la hepatopatía previa.Conclusiones: la mutación C282Y no guarda relación con elriesgo de desarrollar CHC en sujetos sin hemocromatosis conocida.La posesión de la mutación H63D se asocia con un riesgo aumentadode desarrollar CHC independientemente de la etiologíade la hepatopatía crónica subyacente

Aim: to disclose whether mutations in the HFE gene inducingliver iron overload are related to the risk of hepatocellular carcinoma(HCC) in otherwise predisposed patients.Patients and methods: one hundred and ninety-six patients(161 males) diagnosed with HCC and 181 healthy controls wereincluded in the study. All subjects were white Spaniards.C282Y and H63D mutations in the HFE gene were identifiedin leucocyte genomic DNA using a polymerase chain reaction(PCR) and specific restriction enzymes.Results (cases/controls): 1. Genotype distribution: a)C282Y mutation: homozygotes 1/0, heterozygotes 12/23, wildtype 183/158 (p = 0.07, non significant); b) H63D mutation: homozygotes9/5, heterozygotes 85/52, wild type 102/124 (0ddsratio 2.00, 95% C.I. 1.29-3.12, p = 0.002. Four cases and 6controls were carriers of heterozygous mixed genotypes. 2. Allelefrequencies: a) C282Y mutation: wild type allele 378/339, mutatedallele 14/23 (p = 0.11, non significant); b) H63D mutation:wild type allele 289/300, mutated allele 103/62 (0dds ratio1.72, 95% C.I. 1.19-2.50, p = 0.004). Age at diagnosis, genderand etiology of the underlying liver disease do not influence thesefindings.Conclusion: the C282Y mutation in the HFE gene is not relatedto the risk of HCC in non-hemochromatosis patients. TheH63D mutation is associated with a higher risk of HCC in cirrhoticpatients irrespective of their underlying liver disease

[Congenital xerocytosis]. / Xerocitosis congénita.

Hereditary xerocytosis is a genetic disease inherited as an autosomal dominant trait and is a rare cause of hemolytic anemia. It is caused by abnormal erythrocyte membrane permeability: monovalent cation pump activity is increased and the Na/K pump cannot compensate for the K lost. As a consequence, xerocytes dehydrate, becoming rigid and sensitive to metabolic stress and oxidation. Morbility depends on the severity of the hemolytic anemia. Periodic episodes of jaundice are common during mild infections; most patients remain asymptomatic but experience mild-to-moderate hemolytic anemia, which is generally well compensated. The diagnostic clues are a markedly increased flow through the Na/K pump with a decrease in total intracellular cation content and subsequent red cell dehydration. Treatment is based on monitoring for eventual complications and careful observation during infections, which may worsen the anemia. Splenectomy is not useful and for some authors may even be contraindicated. The prognosis is generally very good. We report the case of a patient with episodes of hemolytic anemia during intercurrent infections and positive diagnostic tests for hereditary xerocytosis.

Xerocitosis congénita / Hereditary xerocytosis

La xerocitosis hereditaria es un trastorno genético de herencia autosómica dominante y constituye una causa muy poco frecuente de anemia hemolítica. Se produce por una alteración en la permeabilidad de la membrana eritrocitaria: la actividad de la bomba de cationes monovalentes está aumentada y la bomba sodio-potasio no puede compensar las pérdidas de potasio. Como consecuencia se produce la deshidratación del hematíe, haciéndolo rígido y sensible al estrés metabólico y a los oxidantes. La morbilidad de este cuadro depende del grado de anemia hemolítica que provoque. Con frecuencia existen episodios periódicos de ictericia coincidiendo con infecciones banales, la mayoría de pacientes permanecen asintomáticos con un grado entre leve y moderado de anemia hemolítica, generalmente bien compensada. El marcado incremento del flujo sodio-potasio a través de la membrana del hematíe con descenso en el contenido catiónico total intracelular y la deshidratación del hematíe son las claves diagnósticas. El tratamiento de esta enfermedad se basa en la monitorización de posibles complicaciones y en una observación cuidadosa ante infecciones que pueden dar lugar a exacerbaciones de la anemia. La esplenectomía no es útil, para algunos autores incluso podría estar contraindicada. El pronóstico es, por lo general, bueno. Presentamos el caso de un paciente con episodios de anemia hemolítica coincidiendo con infecciones intercurrentes, con las pruebas diagnósticas de xerocitosis hereditaria (AU)

Receptor sérico de transferrina en niños sanos. Valor diagnóstico en la anemia infecciosa y en la ferropénica / Serum transferrin receptor in healthy children. diagnostic yield in ferropenic and infectious anemia

Antecedentes; El receptor sérico de transferrina (RsTf) ofrece ventajas para evaluar el estado de hierro celular por no alterarse en situaciones de enfermedad aguda o crónica. Objetivo Establecer valores de referencia para nuestro laboratorio del RsTf en niños sanos, conocer la distribución de esta variable en niños con enfermedad aguda y en niños con déficit de hierro, así como evaluar el rendimiento diagnóstico del RsTf para distinguir anemia ferropénica de anemia infecciosa y de sus parámetros relacionados con la ferritina (F): cociente RsTf/F e índice RsTf-F (RsTf/log ferritina).Pacientes y métodos Análisis descriptivo transversal durante un período de 18 meses en 132 niños entre 6 meses y 16 años de edad que fueron divididos en tres grupos: sanos, con enfermedad aguda y con déficit de hierro, estudiando la distribución del RsTf, y evaluando su rendimiento diagnóstico para diferenciar la anemia ferropénica de la anemia que acompaña a enfermedad aguda. Resultados De los 132 pacientes, 30 se excluyeron por no contar con alguno de los parámetros relevantes de este estudio y 19 fueron apartados por ser portadores de rasgo talasémico. En los 30 niños sanos la media del RsTf fue 1,2 mg/l (desviación estándar [DE], 0,36); mediana 1,02 (rango intercuartílico [RIQ], 0,7-1,7). Los 32 niños con enfermedad aguda, con o sin anemia, mostraron valores de RsTf similares a los de niños sanos (p > 0,05). Los valores del RsTf fueron superiores en niños con déficit de hierro (21 niños; RsTf, M 1,67 mg/l; DE, 0,98) que en niños sanos, aunque sin significación estadística (p 0,08). Los valores más altos del RsTf correspondieron a niños con anemia ferropénica (RsTf, M 2,13 mg/l; DE, 1,14), con una diferencia estadísticamente significativa respecto a los niños sanos (p 0,04) y a los niños con ferropenia latente (niños con déficit de hierro pero sin anemia) (p 0,01).El cociente RsTf/F mostró un rendimiento diagnóstico óptimo para distinguir entre anemia ferropénica y anemia por enfermedad aguda. Con valores de este cociente superiores a 80,7 se puede sospechar como causa de la anemia la ferropenia con un valor global de la prueba de 100 por ciento (intervalo de confianza del 95 por ciento [IC 95 por ciento], 75,91-99,42). Conclusiones El RsTf puede ser de utilidad para la evaluación del estado de hierro intracelular en niños. Sus valores no se modifican durante procesos agudos y en combinación con la ferritina ofrece un rendimiento diagnóstico óptimo para distinguir anemia ferropénica de anemia infecciosa (AU)

[Serum transferrin receptor in healthy children. Diagnostic yield in ferropenic and infectious anemia]. / Receptor sérico de transferrina en niños sanos. Valor diagnóstico en la anemia infecciosa y en la ferropénica.

BACKGROUND: The serum transferrin receptor (TfR) presents certain advantages over other parameters of cellular iron status because it does not vary in acute or chronic diseases. OBJECTIVE: To establish reference ranges of TfR in healthy children for our laboratory, to define the distribution of this variable in children with acute illness and in those with iron deficiency, and to evaluate the diagnostic yield of TfR, the transferrin-receptor/ferritin ratio (TfR/F) and the transferrin-receptor-ferritin index (TfR-F) in distinguishing ferropenic from infectious anemia. PATIENTS AND METHODS: A descriptive, cross-sectional analysis was conducted in 132 children aged from 6 months to 16 years for a period of 18 months. The subjects were classified in three groups: healthy children, children with acute illness, and children with iron deficiency. The distribution of TfR and its diagnostic yield were evaluated. RESULTS: Of the 132 subjects, 30 were excluded because they lacked one or more of the parameters under analysis and 19 were excluded because they showed a thalassemic trait. In the 30 healthy children, the mean TfR concentration was 1.2 mg/l (SD 0.36) and the median was 1.02 (IQR 0.7-1.7). In the 32 children with acute illness, with or without anemia, TfR values were similar to those found in healthy children (p > 0.05). TfR values were higher in children with iron deficiency (21 patients; mean TfR value: 1.67 mg/l SD 0:98) than in healthy children but this difference was not statistically significant (p 0.08). The highest TfR values were found in the group with ferropenic anemia (mean TfR value: 2.13 mg/l SD 1.14) with a statistically significant difference between healthy children (p 0.04) and those with iron deficiency without anemia (p 0.01). The TfR/F ratio showed an optimal diagnostic yield in distinguishing ferropenic from acute disease anemia. If this ratio is higher than 80.7 ferropenia can be suspected as the cause of the anemia with a global value of the test of 100 % (95 % CI: 75.91-99.42). CONCLUSIONS: TfR could be useful in evaluating intracellular iron status in children. Acute disease does not alter TfR values and, in combination with ferritin, TfR offers an optimal diagnostical yield in distinguishing ferropenic from acute illness anemia.

[Hematological abnormalities in patients with systemic lupus erythematosus]. / Manifestaciones hematológicas en el lupus eritematoso sistémico.

Haematological abnormalities are frequently encountered in patients with systemic lupus erythematosus (SLE). Anaemia is the most common hematological abnormality in SLE, it is multifactorial. The most common form of anaemia is that of chronic disease, and it is relate with inflammatory cytokines. Other tips of anaemia are: iron deficiency anaemia, autoimmune haemolytic anaemia, pure red cell aplasia. Leucopenia is related to neutropenia and/or lymphopenia. Thrombocytopenia is common, autoimmune and associated with a decreased survival. The presence of antiphospholipid antibodies increase risk of thrombosis in patients with SLE.

Manifestaciones hematológicas en el lupus eritematoso sistémico / Haematological abnormalities in patients with systemic lupus erythematosus

Las alteraciones hematológicas son frecuentes en el lupus eritematoso sistémico (LES). La anemia es la más común y es de naturaleza multifactorial. El tipo más frecuente es la anemia de las enfermedades crónicas, que está en relación con las citoquinas de la inflamación; otros tipos son: la anemia ferropénica, anemia hemolítica autoinmune, aplasia pura de glóbulos rojos. La leucopenia está en relación a la neutropenia y/o linfopenia. La trombocitopenia es común, su causa es autoinmune y se asocia a disminución de la sobrevida. La presencia de anticuerpos antifosfolípidos (AAF) incrementa el riesgo de trombosis en el LES (AU)

C282Y and H63D mutations of HFE gene in patients with advanced alcoholic liver disease.

OBJECTIVE: To test the hypothesis that the heterozygous state for HFE gene mutations involved in the pathogenesis of hemochromatosis, that may induce an increase of hepatic iron content, may aggravate the liver damage induced by prolonged and excessive use of ethanol. PATIENTS AND METHODS: C282Y and H63D mutations of HFE gene were identified through polymerase chain reaction (PCR) on leukocyte DNA, in 125 consecutive patients diagnosed of advanced alcoholic liver disease (109 men, mean age 54 years, SD 11) and 181 healthy controls. All subjects were white Spaniards. RESULTS (CASES/CONTROLS): 1. Genotype distribution: a) mutation C282Y: no homozygotes, 10/23 heterozygotes, 115/158 normal (p = 0.60); b) mutation H63D: 9/5 homozygotes, 46/52 heterozygotes, 70/124 normal (Chi square 6.51, p = 0.039). 2. Allele frequencies: a) mutation C282Y: 240/339 normal, 10/23 mutated (p = 0.21); b) mutation H63D: 186/300 normal, 64/62 mutated (odds ratio 1.66, 95% CI 1.10-2.52, p = 0.01). CONCLUSIONS: Our results suggest that H63D mutation of the HFE gene, but not the C282Y mutation, is associated to the risk of developing advanced liver alcoholic disease.

Mutaciones C282Y y H63D del gen HFE en pacientes con hepatopatía alcohólica avanzada / C282Y and H63D mutations of HFE gene in patients with advanced alcoholic liver disease

Objetivo: examinar la hipótesis de que el estado heterocigoto para las mutaciones del gen HFE involucradas en la patogenia de la hemocromatosis, que puede originar un incremento del contenido hepático de hierro, potencia el daño hepático inducido por el consumo excesivo y prolongado de etanol. Pacientes y métodos: se identificaron las mutaciones C282Y y H63D del gen HFE, mediante reacción en cadena de la polimerasa (PCR) sobre ADN genómico leucocitario, en 125 pacientes consecutivos diagnosticados de hepatopatía alcohólica avanzada (109 varones, edad media 54 años, DE 11) y en 181 controles sanos. Todos los sujetos eran de raza caucasoide y nacionalidad española. Resultados (casos/controles): 1. Distribución genotípica: a) mutación C282Y: ningún homocigoto, 10/23 heterocigotos, 115/158 normales (p = 0,60); b) mutación H63D: 9/5 homocigotos, 46/52 heterocigotos, 70/124 normales (Chi cuadrado 6,51, p=0,039). 2. Frecuencias alélicas: a) mutación C282Y: normales 240/339, mutados 10/23 (p=0,21); b) mutación H63D: normales 186/300, mutados 64/62 (odds ratio 1,66, 95 por ciento IC 1,10-2,52, p=0,011).Conclusiones: nuestros resultados sugieren que la mutación H63D, pero no la mutación C282Y, del gen HFE es un indicador de riesgo para el desarrollo de hepatopatía alcohólica avanzada (AU)

[Analysis of a program for atypical familial microcytosis. Molecular basis of alpha-thalassemia]. / Análisis de un programa de microcitosis familiares atípicas. Base molecular de la alpha-talasemia.

The results of a programme for the study of atypical familial microcytosis are analysed in this paper. The techniques used were "in vitro" synthesis of globin chains in tritiated leucine-labelled reticulocytes and genetic mapping with different restriction enzymes, plus the usual hematologic values. Of the 134 syntheses performed, 73 showed alpha/beta ratio lower than 1 (alpha-thalassaemia). The lowest values, alpha/beta ratio of 0.54 +/- 0.14, corresponded to 3 patients with Hb H disease. In general terms, our findings are similar to those reported in the literature. The genetic mapping was performed in 98 patients with alpha-thalassaemia (73 cases with decreased alpha/beta ratio, 2 cases with normal ratio, and 23 relatives). Of the 98 patients, 3 had Hb H disease, 70 corresponded to heterozygous alpha 0-thalassaemia, 11 to homozygous alpha(+)-thalassaemia, and 14 to heterozygous alpha (+)-thalassaemia. The analysis of DNA revealed the heterogeneity of the molecular alterations, the prevalent haplotypes being (--MED), in 74% of the patients, and (-3.7 alpha), in 100% of the cases. The other alpha zero-thalassaemia mutations found were the deletions (--SEA) and (--SPAN) and the "no-deletion" thalassaemias.

[Hemocytometric and morphologic studies of red cells in cord blood]. / Estudio hemocitométrico y morfológico de la serie roja en la sangre del cordón umbilical.

Authors present red cell indexes of 120 newborns with normal haemoglobin pattern. In the newborn there is an increase of the red cell mass with regard to the infancy and adult life. The lower limit of normality in our environment for MCV is 99.69 fl. The Hb F concentration is 74.70 +/- 10.69%. The differential aspects of the red blood cells in the umbilical cord blood are commented. The influence of several biological variables on the newborn's red cell indexes are described.

[Gaucher's disease of the 3d type (juvenile form)]. / Enfermedad de Gaucher tipo III (forma juvenil).

A case of Gaucher's disease, juvenile type is presented. Disease manifested with signs of hepatosplenomegaly, and thrombocytopenia. The typical Gaucher's cells were found in bone marrow aspiration. Acid phosphatase levels were 1.74 U. Bessey-Lowry/ml, 80.45% corresponding to the non-prostatic fraction. The enzymatic activity of glucosyl ceramide-beta-glucosidase was determined in a fibroblast culture, being its value of 0.42 mU/mg of protein (control: 3.2 mU/mg of protein). We comment on the existing relationship between the clinical types, as well as the therapeutic possibilities.