Avances en el diagnóstico de la enfermedad granulomatosa crónica: primer estudio familiar en Cuba / Advances in the diagnosis of chronic granulomatous disease: the first family study in Cuba

Introducción: La enfermedad granulomatosa crónica es una inmunodeficiencia primaria causada por mutaciones en la enzima NADPH oxidasa. Esta compromete la producción de especies reactivas del oxígeno, que son importantes contra patógenos. La prueba de la oxidación de la dihidrorodamina es un método eficaz para diagnosticar la enfermedad. Objetivo: Demostrar la utilidad de la prueba de la oxidación de la dihidrorodamina y del patrón de herencia en la confirmación del diagnóstico de la enfermedad granulomatosa crónica de un paciente. Métodos: Estudio de caso de una familia con diagnóstico de enfermedad granulomatosa crónica. Se tomó muestra de sangre periférica para citometría de flujo a tres individuos. Se realizó la prueba de la oxidación de la dihidrorodamina bajo estímulo con acetato de forbolmiristato y se evaluaron las subpoblaciones linfocitarias. Las muestras se leyeron en un citómetro GALLIOS, Beckman Coulter. Los datos obtenidos se analizaron en el programa informático Kaluza. Resultados: El paciente masculino tuvo un valor de oxidación de la dihidrorodamina positiva de 0,87 por ciento, que confirmó un patrón de herencia ligado al cromosoma X; mientras que la madre y hermana gemela portadoras tuvieron valores de 46,76 por ciento y 37,32 por ciento, respectivamente. Se encontraron alteraciones en las subpoblaciones linfocitarias. Conclusiones: La prueba de la oxidación de la dihidrorodamina es un método muy efectivo, rápido y sencillo que confirma el diagnóstico de la enfermedad granulomatosa crónica y determina el patrón de herencia y fenotipo de la enfermedad. Además, permite identificar a las mujeres portadoras según la distribución de los neutrófilos normales y los que tienen el gen CYBB mutado(AU)

Introduction: Chronic granulomatous disease is a primary immunodeficiency caused by mutations in the NADPH oxidase enzymes. This compromises the production of oxygen reactive species, which are important against pathogens. The dihydrorhodamine oxidation test is an effective method for diagnosing the disease. Objective: To demonstrate the usefulness of the dihydrorhodamine oxidation test and the inheritance pattern in confirming the diagnosis of chronic granulomatous disease in a patient. Methods: A case study of a family with a diagnosis of chronic granulomatous disease. A peripheral blood sample was taken from three individuals and by flow cytometry. The dihydrorhodamine oxidation test was performed under stimulation with phorbolmyristate acetate, and lymphocyte subpopulations were evaluated. The samples were read on a GALLIOS, Beckman Coulter cytometer. The data obtained were analyzed using the computer program Kaluza. Results: The male patient had a positive dihydrorhodamine oxidation value of 0.87 percent, which confirmed an inheritance pattern linked to the X chromosome; while the carrier mother and twin sister had values 8203;8203;of 46.76 percent and 37.32 percent, respectively. Alterations were found in the lymphocyte subpopulations. Conclusions: The dihydrorhodamine oxidation test is a very effective, fast and simple method that confirms the diagnosis of chronic granulomatous disease and determines the inheritance pattern and phenotype of the disease. In addition, it allows the identification of female carriers according to the distribution of normal neutrophils and those with the CYBB mutation(AU)

A pioneering RET genetic screening study in the State of Ceará, Brazil, evaluating patients with medullary thyroid cancer and at-risk relatives: experience with 247 individuals

ABSTRACT Objective: Initial diagnosis of medullary thyroid carcinoma (MTC) is frequently associated with advanced stages and a poor prognosis. Thus, the need for earlier diagnoses and detection in relatives at risk for the disease has led to increased use of RET genetic screening. Subjects and methods: We performed RET screening in 247 subjects who were referred to the Brazilian Research Consortium for Multiple Endocrine Neoplasia (BRASMEN) Center in the State of Ceará. Direct genetic sequencing was used to analyze exons 8, 10, 11, and 13-16 in MTC index cases and specific exons in at risk relatives. Afterward, clinical follow-up was offered to all the patients with MTC and their affected relatives. Results: RET screening was performed in 60 MTC index patients and 187 at-risk family members. At the initial clinical assessment of the index patients, 54 (90%) were diagnosed with apparently sporadic disease and 6 (10%) diagnosed with hereditary disease. After RET screening, we found that 31 (52%) index patients had sporadic disease, and 29 (48%) had hereditary disease. Regarding at-risk relatives, 73/187 were mutation carriers. Mutations in RET codon 804 and the rare p.M918V mutation were the most prevalent. Conclusions: Performing RET screening in Ceará allowed us to identify a different mutation profile in this region compared with other areas. RET screening also enabled the diagnosis of a significant number of hereditary MTC patients who were initially classified as sporadic disease patients and benefited their relatives, who were unaware of the risks and the consequences of bearing a RET mutation.

Prevalência de heterozigotos para hemoglobinopatias em estudantes universitários do Ceará / The prevalence of heterozygotes for hemoglobinopathies among undergraduate students of Ceará

As hemoglobinopatias são doenças genéticas freqüentes que apresentam morbidade significativa em todomundo. A detecção de heterozigotos AS e AC é extremamente importante para a saúde pública, uma vez que essesindivíduos podem originar indivíduos homozigotos SS ou duplos heterozigotos SC. O presente estudo teve como objetivo determinar a prevalência de heterozigotos para hemoglobinopatias em estudantes universitários do Ceará e, em seguida, encaminhá-los para um profissional habilitado em aconselhamento genético. Do total de 235 amostras analisadas, 229(97,5%) apresentaram perfil hemoglobínico normal (Hb AA), enquanto que em 6 (2,5%) foram identificadas hemoglobinas anormais. Destas, 5 (2,1%) apresentaram traços de hemoglobina S (heterozigose AS) e 1 (0,4%) amostra apresentou traços de hemoglobina C (heterozigose AC). A triagem de hemoglobina é importante para a prevenção de hemoglobinopatias, principalmente para os indivíduos que não foram beneficiados com a Portaria n° 822/01 do Ministério da Saúde que incluiu as hemoglobinopatias no Programa Nacional deTriagem Neonatal e, portanto, desconhecem o fato deserem portadores assintomáticos.

Hemoglobinopathies are quite common genetic diseases which present significant morbity worldwide. Theearly detection of AS and AC heterozygotes among prospective couples is of extreme importance in Health Public Policy making, since those individuals may give birth to homozygotes SS or double-heterozygotes, SC. This study aims todetermine the prevalence of heterozygotes for hemoglobinopathies among undergraduate students of Ceará and then direct them to genetic counseling. Of the 235 samples analyzed, 229 (97.5%) had a normal hemoglobinic profile (Hb AA), while 6(2.5%) had abnormal hemoglobin. From the former, 5 (2.1%) samples presented traces of Hemoglobin S (AS heterozygose), and only 1 (0.4%) hemoglobin C (AC heterozygose). Hemoglobin tracing is a vitally important public health policy in the prevention of hemoglobinopathies, especially among individuals who have not benefited from the Brazilian Ministry of Health Directive # 822/01, which includes hemoglobinopathies in the National Neonatal Screening Program consequently they are unaware of being asymptomatic carriers.

Preventive aspects of genetic morbidity: experiences of the Canadian model

Genetic disorders are emerging as a major health problem in industrialized countries, especially with greater control of environmental diseases. Of total admissions to major paediatric hospitals, 50% are due to genetic disorders, and at least 10% of all adult admissions to hospitals involve major genetic contributions. Several programmes aimed at preventing or ameliorating these genetic disorders are being implemented. Identifying people at risk of genetic disease has helped decrease the burden of such diseases on families and society. Early recognition also leads to greater success of treatment and improves outcome and prognosis. In Arab populations, genetic disorders are still not perceived as a major health problem, even though they are widely prevalent. Applying similar programmes of early detection, maternal screening, neonatal screening, carrier testing and susceptibility testing will significantly help reduce the impact of these disorders in our populations

Detecçäo de distúrbios metabólicos em deficientes mentais em Salvador - Ba / Detection of metabolic disorders in institutionalized mentally deficent patients in Salvador, Bahia

O presente estudo teve como objetivo determinar a freqüência de distúrbios metabólicos em deficientes mentais institucionalizados em Salvador-BA e em pacientes atendidos no Laboratório de Genética Médica do HIPES no ano de 1989. No 1§ grupo de pacientes, foram selecionados 297 indivíduos com deficiência mental moderada, ou grave, ou profunda sem diagnóstico etiológico estabelecido. Destes, 258 indivíduos foram submetidos à avaliaçäo laboratorial para detecçäo de distúrbios metabólicos, por intermédio da realizaçäo de uma bateria de técnicas de triagem. No 2§ grupo foram atendidos no Laboratório de Genética do HUPES 65 pacientes, encaminhados para investigaçäo de erro inato do metabolismo (EIM), apresentando sinais ou sintomas que sugerissem a suspeita diagnóstica de EIM. Em todos foram realizadas técnicas de triagem. Os indivíduos que apresentaram alteraçöes nas técnicas de triagem foram submetidos à avaliaçäo diagnóstica. No primeiro grupo, distúrbios metabólicos foram detectados em 1,55// dos deficientes, näo sendo possível estabelecer o diagnóstico final em nenhum deles. No segundo grupo, 8 pacientes (12,31//) apresentaram alteraçöes nas técnicas de triagem. Estes e mais 22 pacientes com triagem normal, mas com quadro clínico sugestivo de EIM näo detectável pelas técncias de triagem, foram selecionados para investigaçäo diagnóstica. Distúrbios metabólicos foram detectados em 12 pacientes (18,46// do total), porém em apenas 6 pacientes um diagnóstico específico de EIM foi estabelecido, correspondendo a uma freqüência de 9,23// do total de pacientes