Coenzyme Q10 and pro-inflammatory markers in children with Down syndrome: clinical and biochemical aspects / Coenzima Q10 e marcadores pró-inflamatórios em crianças com síndrome de Down: aspectos clínicos e bioquímicos

Abstract: Objective: Evidence of oxidative stress was reported in individuals with Down syndrome. There is a growing interest in the contribution of the immune system in Down syndrome. The aim of this study is to evaluate the coenzyme Q10 and selected pro-inflammatory markers such as interleukin 6 and tumor necrosis factor α in children with Down syndrome. Methods: Eighty-six children (5-8 years of age) were enrolled in this case-control study from two public institutions. At the time of sampling, the patients and controls suffered from no acute or chronic illnesses and received no therapies or supplements. The levels of interleukin 6, tumor necrosis factor α, coenzyme Q10, fasting blood glucose, and intelligence quotient were measured. Results: Forty-three young Down syndrome children and forty-three controls were included over a period of eight months (January-August 2014). Compared with the control group, the Down syndrome patients showed significant increase in interleukin 6 and tumor necrosis factor α (p = 0.002), while coenzyme Q10 was significantly decreased (p = 0.002). Also, body mass index and fasting blood glucose were significantly increased in patients. There was a significantly positive correlation between coenzyme Q10 and intelligence quotient levels, as well as between interleukin 6 and tumor necrosis factor α. Conclusion: Interleukin 6 and tumor necrosis factor α levels in young children with Down syndrome may be used as biomarkers reflecting the neurodegenerative process in them. Coenzyme Q10 might have a role as a good supplement in young children with Down syndrome to ameliorate the neurological symptoms.

Resumo: Objetivo: Foram relatadas evidências de estresse oxidativo em indivíduos com a síndrome de Down. Há um interesse cada vez maior na contribuição do sistema imunológico na síndrome de Down. O objetivo deste estudo é avaliar a coenzima Q10 e marcadores pró-inflamatórios selecionados, como interleucina 6 e o fator de necrose tumoral α, em crianças com a síndrome de Down. Métodos: Foram inscritas neste estudo de caso-controle 86 crianças (5-8 anos) de duas instituições públicas. No momento da amostragem, os pacientes e os controles não sofriam de doença aguda ou crônica e não recebiam terapia ou suplementos. Foram medidos os níveis de interleucina 6, fator de necrose tumoral α, coenzima Q10, glicemia de jejum e quociente de inteligência. Resultados: Foram incluídas em oito meses (janeiro-agosto 2014) 43 crianças com síndrome de Down e 43 controles. Em comparação com o grupo de controle, os pacientes com síndrome de Down mostraram aumento significativo na interleucina 6 e no fator de necrose tumoral α (p = 0,002), ao passo que a coenzima Q10 apresentou significativa redução (p = 0,002). Além disso, o índice de massa corporal e a glicemia de jejum eram significativamente maiores nos pacientes. Houve uma correlação significativamente positiva entre os níveis de coenzima Q10 e do quociente de inteligência, bem como entre a interleucina 6 e o fator de necrose tumoral α. Conclusão: Os níveis de interleucina 6 e o fator de necrose tumoral α em crianças mais novas com síndrome de Down podem ser usados como biomarcadores, refletem o processo neurodegenerativo neles. A coenzima Q10 pode ter um papel como bom suplemento em crianças com síndrome de Down para melhorar os sintomas neurológicos.

TSH neurosecretory dysfunction (TSH-nd) in Down syndrome (DS): low risk of progression to Hashimoto's thyroiditis / Disfunção neurossecretora de TSH na síndrome de Down: baixo risco de progressão para a tireoidite de Hashimoto

INTRODUCTION: Patients with Down syndrome (DS) often have elevated TSH (hypothalamic origin), which is called TSH neurosecretory dysfunction (TSH-nd). In these cases, there is slight elevation in TSH (5-15 µUI/mL), with normal free T4 and negative thyroid antibodies (AB). OBJECTIVE: To recognize the risk of progression to Hashimoto's thyroiditis (HT). SUBJECTS AND METHODS: We retrospectively analyzed 40 DS patients (mean age = 4.5 years), followed up for 6.8 years. RESULTS: HT was diagnosed in 9/40 patients, three early in monitoring, and six during evolution. In 31/40 patients, TSH-nd diagnosis remained unchanged over the years, with maximum TSH values ranging from 5 to 15 µUI/mL. In this group, free T4 also remained normal and AB were negative. There was a significant TSH reduction (p = 0.017), and normal TSH concentrations (< 5.0 µUI/mL) were observed in 29/31 patients, in at least one moment. No patient had TSH > 15 µUI/mL. CONCLUSION: DS patients with TSH-nd present low risk of progression to HT (10 percent for females and 6 percent for males).

INTRODUÇÃO: Pacientes com síndrome de Down (SD) geralmente apresentam TSH elevado (de origem hipotalâmica), uma desordem chamada de disfunção neurossecretora de TSH (TSH-nd). Nesses casos, há uma leve elevação do TSH (5-15 µUI/mL), com T4 livre normal e anticorpos antitireoide (AB) negativos. OBJETIVO: Reconhecer o risco de progressão para a tireoidite de Hashimoto (HT). SUJEITOS E MÉTODOS: Analisamos retrospectivamente 40 pacientes com SD (idade média = 4,5 anos), acompanhados por 6,8 anos. RESULTADOS: A HT foi diagnosticada em 9/40 pacientes, três logo no início da avaliação e seis durante a evolução. Em 31/40 dos pacientes, o diagnóstico de TSH-nd permaneceu estável durante os anos, com valores máximos de TSH variando de 5 a 15 µUI/mL. Neste grupo, o T4 livre também permaneceu normal e os AB foram negativos. Houve uma redução significativa do TSH (p = 0,017), e concentrações normais de TSH (< 5,0 µUI/mL) foram observadas em 29/31 pacientes, em pelo menos um momento. Nenhum paciente apresentou TSH > 15 µUI/mL. CONCLUSÃO: Pacientes com SD e TSH-nd apresentam baixo risco de progressão para a HT (10 por cento para o sexo feminino e 6 por cento para o sexo masculino).

The cytogenetic examination as a tool for the diagnosis of chromosomal disorders / Examinación citogenética como herramienta para el diagnóstico de los desórdenes cromosómicos

Clinically significant chromosomal abnormalities occur in about 1 percent of children born alive. The objective of this work was to offer the patients and the families in the community for the service of the Integrated Clinic of Uniara Health (Araraquara and region), the examination of cariotype (cytogenetic study) for confirmation or exclusion of the diagnostic suspicion of chromosomal abnormalities as well as information (genetic counseling) for the prevention of occurrence and/or recurrence of these anomalies. In the period of one year and four months these were carried out in the Integrated Clinic of Uniara Health and directed for the Laboratory of Cytogenetic Human of the same institution in 66 cytogenetic studies. In 44 patients (66.6 percent) the results were normal. In 22 (33.3 percent) examinations, alterations were found, meaning that the respective clinical pictures are decurrent of chromosomic alterations. The first cause within alterations noted was Down syndrome with a total of 15 examinations or 68.1 percent, the second cause of chromosomal anomaly was the Turner syndrome where the most important factor is 45, X, where 2 karyotypes of this type or 9.1 percent were found, syndromes as (Eduards syndrome, Patau syndrome, 3p- syndrome, 4p- syndrome and 6p-syndrome) diagnosed in our laboratory appeared less frequently corresponding to 22.7 percent of the studied anomalies. The work carried out constitutes a necessary diagnosis of the main chromosomal abnormalities through a low cost technique; it can be carried out easily and is reliable, making the cytogenetic examination available to the community and contributing significantly to the quality of life of patients.

Las anormalidades cromosómicas, clínicamente significativas, se presentan en aproximadamente 1 por ciento de los niños nacidos vivos. Este trabajo tiene el objetivo de ofrecer a los pacientes y /o a sus familiares el servicio de la Clínica Integrada de la Salud de Uniara (Araraquara y Región), el examen de cariotipo (estudio citogenético) para la confirmación o la exclusión de sospecha de anomalías cromosomales diagnosticadas, así como otorgar información (consejo genético) para la prevención de las posibles anomalías y /o la repetición de éstas. En un año y cuatro meses fueron realizados 66 estudios de citogenética en la Clínica Integrada de Uniara, dirigida por el Laboratorio de Citogenética Humana de la misma institución. En 44 pacientes (66,6 por ciento) los resultados fueron normales. En 22 (33,3 por ciento) de los exámenes, se encontraron alteraciones, compatibles con alteraciones cromosómicas. La primera causa de anomalías cromosómica fue el síndrome de Down, totalizando 15 exámenes (68,1 por ciento), la segunda causa fue el síndrome de Turner, con dos cariotipos (9,1 por ciento) en la forma más importante 45, X. Por otra parte, se encontró que los síndromes de Eduards, de Patau, 3p-síndrome de Down, síndrome 4p-6p, diagnosticados en nuestro laboratorio, presentaban baja frecuencia de aparición, representando el 22,7 por ciento de las anomalías estudiadas. Este trabajo permitió realizar un diagnóstico preciso de las anomalías cromosomales, principalmente a través de una técnica de bajo costo, fácil ejecución y buena confiabilidad, técnicas que están disponibles para el examen citogenético para la comunidad y así contribuir de manera significativa en la calidad de vida de los pacientes.

Korean-Specific Parameter Models for Calculating the Risk of Down Syndrome in the Second Trimester of Pregnancy

The purpose of the current study was to propose a Korean-specific parameter set for calculating the risk of Down syndrome in the second trimester of pregnancy and to determine the screening performances of triple and quadruple tests in Korean women. Using the data on triple or quadruple screening from three hospitals in Korea during 7 yr, we re-converted the concentrations of four serum markers to multiple of median values according to gestational age and maternal weight. After re-calculating the risk of Down syndrome in each pregnancy by multiplying maternal age-specific risk by the likelihood ratio values for the serum markers, screening performances and optimal cut-off values of triple and quadruple tests were analyzed. Among 16,077 pregnancies, 23 cases had Down syndrome (1.4/1,000 deliveries). Compared to the previous program, the tests with new parameters had improved screening performance. The triple and quadruple tests had detection rates of 65.2% and 72.7%, respectively, at a false-positive rate of 5%. The optimal cut-off value for the quadruple and triple tests was 1:250. We have presented a Korean-specific parameter set for Down syndrome screening. The proposed screening test using this parameter set may improve the performance of Down syndrome screening for Korean women.

The MTR A2756G polymorphism is associated with an increase of plasma homocysteine concentration in Brazilian individuals with Down syndrome

Individuals with Down syndrome (DS) present decreased homocysteine (Hcy) concentration, reflecting a functional folate deficiency secondary to overexpression of the cystathionine ß-synthase gene. Since plasma Hcy may be influenced by genetic polymorphisms, we evaluated the influence of C677T and A1298C polymorphisms in the methylenetetrahydrofolate reductase gene (MTHFR), of A2756G polymorphism in the methionine synthase gene (MTR), and of A80G polymorphism in the reduced folate carrier 1 gene on Hcy concentrations in Brazilian DS patients. Fifty-six individuals with free trisomy 21 were included in the study. Plasma Hcy concentrations were measured by liquid chromatography_tandem mass spectrometry with linear regression coefficient r² = 0.9996, average recovery between 92.3 to 108.3 percent and quantification limits of 1.0 µmol/L. Hcy concentrations >15 µmol/L were considered to characterize hyperhomocystinemia. Genotyping for the polymorphisms was carried out by polymerase chain reaction followed by enzyme digestion and allele-specific polymerase chain reaction. The mean Hcy concentration was 5.2 ± 3.3 µmol/L. There was no correlation between Hcy concentrations and age, gender or MTHFR C677T, A1298C and reduced folate carrier 1 A80G genotype. However, Hcy concentrations were significantly increased in the MTR 2756AG heterozygous genotype compared to the MTR 2756AA wild-type genotype. The present results suggest that the heterozygous genotype MTR 2756AG is associated with the increase in plasma Hcy concentrations in this group of Brazilian patients with DS.

Homocysteine, an indicator of methylation pathway alternation in Down syndrome and its regulation by folic acid therapy

Down syndrome [DS] is a complex genetic disease. Some clinical features of patients with this syndrome could be related to functional folate deficiency. The purpose of this study was to evaluate the total homocysteine [T-Hcy] metabolism in DS children and to determine whether the supplementation with folic acid therapy would shift the genetically induced metabolic imbalance or not. Thirty-five infants with DS, with the mean age of 17.66 +/- 12.24 months were included in this study. They were selected from those attending the Genetic Outpatients Clinic in Children hospital. Our results revealed that Down syndrome children had a significant decrease in serum plasma T-Hcy level after the treatment with folic acid [11.79: +/- 0.92 vs. 14.41 +/- 4.93 micro mol/L]. A significant negative correlation was found between T-Hcy and folic acid serum levels [r = -0.112; P<0.05]. We concluded that the regulation of methylation pathways in Down syndrome patients becomes important in the light of possible normalization of the metabolic imbalance and the detection of increased sensitivity to therapeutic interventions

Medidas antropométricas como predictores del comportamiento lipídico sérico en adolescentes con síndrome de Down / Anthropometrical measurements as predictor of serum lipid profile in adolescents with Down syndrome

Current findings suggest that more attention needs to be given to the increase in body mass being achieved by disabled populations in general and individuals with mental retardation in particular, to minimize long-term negative health consequences. Given that physical activity programs have been reported as one of the most effective ways of improving the health of individuals with Down syndrome, it would be of interest facilitate different tools to contribute to their clinical follow-up. Consequently, this study was designed to assess the correlation between anthropometrical parameters and lipid profile in adolescents with Down syndrome. Anthropometric variables such as body mass index, waist circumference and waist-to-hip ratio as well as serum lipids (total cholesterol, high-density-lipoprotein cholesterol, total-choles-terol/high-density-lipoprotein cholesterol and triglycerides) were measured in 21 male adolescents (16.3 ± 1.1 years) with Down syndrome. Anthropometric parameters presented a positive association with serum lipids except for high-density-lipoprotein cholesterol that was negative. It should be emphasized the strongest association of waist-to-hip ratio to total cholesterol/high-density-lipoprotein cholesterol ratio (r = 0.48; p < 0.05). It is concluded waist circumference and waist-to-hip ratio may be highly recommended in clinical practice as appropriate anthropometric predictors of lipid profile in adolescents with Down syndrome. Further studies are required to assess their behavior during physical activity programs as well as to determine more correlations in these individuals.

Si la obesidad como epidemia está alcanzando cotas preocupantes en la población general, la situación es aún más alarmante entre poblaciones con retraso mental en general y síndrome de Down en particular. Afortunadamente, recientes estudios sugieren que los programas de actividad física parecen una buena estrategia para combatirla, especialmente a edades tempranas. Para facilitar el seguimiento clínico de los mismos, diseñamos este trabajo para determinar las correlaciones más significativas entre parámetros antropométricos (índice masa corporal; índice cintura cadera; perímetro cadera) y el perfil lipídico sérico (colesterol total; colesterol-HDL; ratio colesterol total/HDL; triglicéridos) de 21 jóvenes adolescentes (16.3 ± 1.1) con trisomía 21. El coeficiente de correlación de Pearson demostró que las variables antropométricas ensayadas mostraron una correlación positiva con los distintos parámetros lipidicos excepto para colesterol-HDL que fue negativa. En líneas generales el perímetro de la cintura mostró el mejor comportamiento, mientras el índice cintura cadera mostró la mayor fuerza de asociación con la ratio colesterol-total/colesterol-HDL (r = 0.48; p < 0.05). Futuros estudios en los que se confirme la utilidad de estos hallazgos durante la aplicación de programas de actividad física y en los que se evalúen nuevas asociaciones son necesarios para contribuir a un mejor seguimiento y manejo de estos pacientes.

Adverse pregnancy outcomes after a false-positive second trimester serum screen for Down syndrome in Thai pregnant women.

OBJECTIVE: To determine whether a false-positive second trimester serum screen for Down syndrome in Thai pregnant women is predictive of adverse pregnancy outcomes. MATERIAL AND METHOD: The relationship between adverse pregnancy outcomes in women and a false-positive screening for Down syndrome was investigated in a case-control study. The Double-marker maternal serum screening for Down syndrome (alpha-fetoprotein and free beta-hCG) was performed on Thai pregnant women between 14 and 21 weeks 'gestation at Charoenkrung Pracharuk Hospital from March 1998 to August 2002. The pregnancy outcomes of 165 women having false positive serum screening (risk ratio at least 1.270; study group) were compared to the outcomes of 165 control patients having negative serum screening results (control group). The outcome indices analyzed were preterm delivery, low birth weight newborn, small-for-gestational age newborn, preeclampsia, placenta previa, and fetal death. RESULTS: The incidence of adverse pregnancy outcomes was 18.2% in the study group and 15.2% in the control group (odds ratio = 1.244; 95% confidence interval = 0.696, 2.225; p = 0.46). Women in the study group delivered at a significantly lower birth weight of newborns than women in the control group did (3088.1 +/- 543.9 versus 3229.1 +/- 454.6 g, respectively; p = 0.011). No significant differences in adverse outcomes was discovered after the comparisons between the study group and the control group. preterm delivery 11 of 165 (6.6%) versus 5 of 165 (3%), p = 0.124; low birth weight newborn 11 of 165 (6.6%) versus 6 of 165 (3.6%), p = 0.213; small for gestational age newborn 4 of 165 (2.4%) versus 0 of 165 (0%), p = 0.123; preeclampsia 16 of 165 (9.7%) versus 12 of 165 (7.3%), p = 0.429; placenta previa 4 of 165 (2.4%) versus 4 of 165 (2.4%), p=1; fetal death 1 of 165 (0.6%) versus 0 of 165 (0%), p=1. CONCLUSION: The present findings revealed no apparent increase in the adverse pregnancy outcomes analyzed in women with false positive Down syndrome screening test.

Avaliação etiológica da hipertirotropinemia em crianças com síndrome de Down / Etiological assessment of hyperthyrotropinemia in children with Down's syndrome

OBJETIVO: Analisar a prevalência de hipertirotropinemia e estudar sua possível etiologia em crianças com síndrome de Down atendidas na Policlínica Municipal Antônio Cândido, em Belo Horizonte. MÉTODOS: Foram utilizados os dados dos prontuários de todas as crianças com síndrome de Down atendidas na policlínica para o cálculo da prevalência da alteração do hormônio estimulante da tireóide (TSH). As crianças que tiveram TSH elevado (maior que 5 µUI/ml) em pelo menos um exame foram convocadas para novas dosagens de TSH, T4livre, T4total e auto-anticorpo antiperoxidase (ATPO), realização de ultra-som da tireóide, tireograma com iodo-131 e teste de descarga do perclorato. As alterações encontradas nos exames das crianças que permaneceram com TSH elevado foram comparadas com as das que normalizaram os valores de TSH. RESULTADOS: Foram encontradas, em 169 crianças com síndrome de Down, 86 (50,8 por cento) masculinas, idade entre 1-6 anos (mediana de 4 anos), 67 (39,6 por cento) com TSH aumentado, as quais foram convocadas para novas avaliações, comparecendo 46. Nesses pacientes, o TSH se normalizou em 31 (67,4 por cento); em 11 (23,9 por cento) permaneceu entre 5-10 µUI/ml; em três (6,5 por cento) ficou acima de 10 µUI/mL; e em uma (2,2 por cento) constatou-se hipertireoidismo. Os diagnósticos realizados nos pacientes com propedêutica completa (n = 34) foram: bócio (14,7 por cento), hipoplasia (8,8 por cento), tireoidite de Hashimoto (5,9 por cento), defeito na organogênese de iodo (2,9 por cento). Não se evidenciou relação entre as amplitudes dos valores de TSH e a persistência da hipertirotropinemia. Crianças com ATPO positivo estavam associadas a TSH elevado (p = 0,02). CONCLUSÕES: Na síndrome de Down, são freqüentes valores de TSH discretamente elevados e instáveis, sendo suas etiologias variáveis. A presença de ATPO mostrou-se importante no seguimento dessas crianças pelo risco potencial de evolução para doença tireoidiana manifesta.

Maternal serum screening of Palestinian women in the West Bank

An audit was made of laboratory records of triple test results from 943 Palestinian women residing in the West Bank from 2000-03. The mean expected age at delivery of the subjects was 25.5 years; 12% were 35 years old or above. Age was the main factor associated with an abnormal calculated risk score. The frequency of elevated serum alpha-fetoprotein was 1.3%, abnormal human choriogonic gonadotropin [elevated or reduced] was 1.9% and reduced unconjugated estriol was 0.3%

Hallazgos citogenéticos en pacientes con síndrome de Down / Cytogenetic findings in patients with Down syndrome

Con el objeto de establecer la frecuencia de trisomia 21 no clásicas se analizaron los estudios cromosómicos de 201 pacientes, derivados para estudio citogenético en linfocitos de sangre periférica con el diagnóstico clínico de síndrome de Down. De éstos, 161 (80%) resultaron trisomías 21 clásicas, 7(3,5%) trisomías 21 por translocación, 5(2,5%) trisomías 21 en mosaico, 6(3%) trisomías 21 más otra alteración cromosómica y 22(11%) tenía estudios citogenéticos normales. En 26,8% de los pacientes el diagnóstico fue hecho en el período de recién nacido y la proporción de hombres y mujeres fue de (1,18:1)

Estudio de los niveles de colesterol total y lipoproteico en pacientes con síndrome de Down / Study of total cholesterol and lipoprotein levels in patients with Down's syndrome

Se realizó una comparación de los niveles del colesterol en el plasma y en cada una de las fracciones lipoproteicas, entre niños con síndrome de Down y niños normales. Se destaca que la técnica de determinación del colesterol empleado se basa en un principio químico colorimétrico y la separación de las fraciones se realiza por precipitación selectiva con heparina Mm. Se informa que en el tratamiento de las muestras ambas fueron separadas en grupos de sexo diferentes a los efectos de los análisis comparativos y la aplicación de los tests estadísticos empleados. Se concluye que los resultados evidencian la existencia de niveles elevados del colesterol-VLDL en los niños con SD, respecto a los normales

Factor tímico sérico en pacientes de síndrome de Down / Serum thymic factor in patients with Down syndrome

Se ha demostrado un factor sérico con actividad biológica similar al de la timosina, denominado factor tímico sérico (FTS). En el hombre se ha evaluado la actividad de este factor por la prueba de rosetas en padecimientos autoinmunitarios y en inmunodeficiencias. En los pacientes con síndrome de Down se ha demostrado una mayor frecuencia de infecciones, enfermedades malignas y autoanticuerpos, y se ha sugerido que estas alteraciones pueden deberse a un defecto inmunológico en las células no diferenciadas. La finalidad de este artículo fue medir la actividad biológica del FTS en síndrome de Down, ataxia telangiectásica y niños sanos. Se estudió un grupo de l5 niños con síndrome de Down, edades de dos meses a dos años y otro grupo de cinco, con edades de diez a l5 años, diagnóstico de ataxia telangiectásica, identificados con FTS disminuido en actividad biológica, comparándolos con un grupo de testigos sanos que se formó con 12 pacientes de tres meses a tres años y cinco niños sanos de diez a 13 años. A todos los pacientes se les midió la actividad del FTS por la prueba de rosetas, y se cuantificó la subpoblación de linfocitos T circulantes. La actividad biológica del FTS fue menor que la observada con el suero de niños sanos (p < 0.01); en la subpoblación de rosetas se encontraron cifras de LFR-E-mm/3 713.8 + ou - 128 y en niños sanos de 932 + ou - 64 LFR-E/mm3, que, al ser comparadas, mostraron diferencias significativas (p < 0.001)

Estudio de los niveles de triglicéridos en pacientes con Síndrome de Down / Triglyceride levels in patients with Down's syndrome

Se realiza un estudio comparativo de los niveles de concentración de triglicéridos en 38 niños afectados por trisomía del par cromosómico 21 y una muestra control de niños normales, ambas fueron analizadas por grupos de edad, peso corporal y sexo. Se realizó la determinación de triglicéridos por el método químico indirecto. Se encuentran diferencias significativas entre los niveles de triglicéridos de niños normales y trisómicos y fueron más elevados en estos últimos, mientras que el análisis entre normales y trisômicos para igual rango de peso corporal no dio diferencias significativas. Se señala que los niveles de triglicéridos en niños con síndrome de Down no están correlacionados significativamente con los niveles en sus padres