RESUMEN
Living organisms are exposed to exogenous and endogenous agents that affect genomic integrity by creating DNA double strand breaks (DSBs). These breaks are repaired by DNA repair proteins to maintain homeostasis. Defects in DNA repair pathways also affect lymphocyte development and maturation, as DSB sites are critical intermediates for rearrangements required for V(D)J recombination. Recent classifications for inborn errors of immunity (IEIs) have listed DNA repair defect genes in a separate group, which suggests the importance of these genes for adaptive and innate immunity. We report an interesting case of a young female (index P1) with mutations in two different genes, DCLRE1C and FANCA, involved in DNA repair pathways. She presented with clinical manifestations attributed to both defects. With the advent of NGS, more than one defect is increasingly identified in patients with IEIs. Familial segregation studies and appropriate functional assays help ascertain the pathogenicity of these mutations and provide appropriate management and genetic counseling.
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Bioensayo , Anemia de Fanconi , Humanos , Femenino , Genómica , Homeostasis , Inmunidad InnataRESUMEN
Measles-rubella (MR) vaccine-associated encephalopathy is rare and coexistence with optic neuritis (ON) has never been reported. Only two patients (one child and one adult) had 'MR Vaccine-associated myelin-oligodendrocyte-glycoprotein antibody (MOGAb) positive encephalopathy'. Myelin oligodendrocyte glycoprotein (MOG), a surface myelin protein, is the target of the immune system in this disease. We describe a critical unique case of 'post-MR Vaccine, MOG-antibody positive Acute Disseminated Encephalo-Myelitis (ADEM) with optic neuritis', who recovered with immunotherapy.
RESUMEN
OBJECTIVE: To assess the growth and sexual maturity of non-handicapped children with birth weight less than 2000 g at 12 years. DESIGN: Prospective cohort study. SETTING: Infants discharged from a Neonatal Special Care Unit of a referral hospital with birth weight less than 2000 g between 1987-1989 and followed up till the age of 12 years. METHODS: The height, weight and head circumference was measured. Sexual maturity was determined by Tanners score and age of menarche in girls was reported by parents. Parental height and weight was recorded. Intelligence quotient was determined by Weschslers Intelligence Scale. RESULTS: The cohort of 180 low birth weight (LBW) infants (birth weight less than 2000 g) was divided into 3 groups according to their gestation - preterm SGA (n=73), full term SGA (n=33) and preterm AGA (n=74). Ninety full term AGA infants served as controls. Preterm SGA children had significantly less height (mean deficit 5.8 cm), weight and head circumference (P<0.001). There was no significant difference in sexual maturity and onset of menarche between the study group and controls. There was a correlation between head circumference and IQ and preterm SGA children had the lowest mean IQ (85.4 +/- 17.7). Mothers height contributed 14% variance to a total variance of 25.3% for Z score of height at 12 years. Mothers weight contributed a variance 21.1% to a total variance of 29.4% for Z score of weight. CONCLUSION: Preterm SGA children were shorter, lighter and had the smallest head circumference, and also had the lowest IQ. Mothers height and weight was an important determinant of height and weight at 12 years.
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Tamaño Corporal , Trastornos del Crecimiento/epidemiología , Recién Nacido de Bajo Peso , Recién Nacido Pequeño para la Edad Gestacional , Maduración Sexual , Adiposidad , Adolescente , Factores de Edad , Antropometría , Estudios de Casos y Controles , Niño , Femenino , Indicadores de Salud , Humanos , Recién Nacido , Masculino , Estudios Prospectivos , Psicometría , Escalas de WechslerRESUMEN
BACKGROUND: To study the early markers of Metabolic syndrome in a cohort of low birth weight (LBW) children followed up since birth, at the age of 22 years. DESIGN: Prospective cohort study. SETTING: Tertiary-care hospital. PARTICIPANTS: Neonates weighing less than 2000 g discharged from a neonatal special care unit were followed up prospectively; 153 cases and 77 controls were assessed at 22 years of age. METHODS: Fasting, 30 minute and 120 minute glucose and insulin after a bolus of 75g of glucose was determined. Insulin resistance was calculated. A lipid profile was also done. Anthropometric measurements were taken and abdominal fat was determined by magnetic resonance imaging. MAIN OUTCOME: Prevalence of the five components of Metabolic Syndrome as described by the International Diabetic Federation (IDF). RESULTS: 65.1% of the cohort was born small for gestational age. All three components of Metabolic syndrome were present in only three cases and none of the controls. However, two components were present in 25 (16.4%) cases and 5 (6%) controls (P=0.039). Cases in the lowest quartile of birthweight who became big at 22 years had significantly higher fasting insulin (P=0.001), Homeostatic Model Assessment - Insulin Resistance (Homa-IR) (P=0.001) and higher systolic blood pressure. Sum of skinfold thickness at 4 sites correlated significantly with fasting insulin and HOMA-IR, and was a stronger correlate compared to BMI, waist circumference and MRI fat. There was no difference in the biochemical parameters between appropriate for gestational age and small for gestational age infants. CONCLUSION: Prevelence of three or more components of Metabolic syndrome was low in LBW children at 22 years, but of two components was high. Those 'Small at birth and big at 22 years' had high insulin resistance.
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Recién Nacido de Bajo Peso , Síndrome Metabólico/epidemiología , Adulto , Glucemia/análisis , Femenino , Estudios de Seguimiento , Humanos , Hipertensión , Resistencia a la Insulina , Lípidos/sangre , Masculino , Estudios Prospectivos , Adulto JovenRESUMEN
OBJECTIVE: To explore the contribution of biologic risk factors versus socio-demographic and environmental risk factors in cognitive development of children with birth weight less than 2000 g, at the age of 12 years. DESIGN: Prospective cohort study. SETTING: Infants discharged from a NICU of a referral hospital, with birth weight less than 2000 g between 1987-89 and followed up in the High Risk Clinic. METHODS: The children were assessed at the age of 12 years, with the Weschler's Intelligence Scale for IQ and by Wide Range Achievement Test for mathematics skills. Mother's education, father's education, socio-economic status, family structure, spaciousness of the house, the locality in which the child lived and the type of school the child attended, were all recorded. A stimulation score was determined at 6 and 12 months and 3 years. Family environment score was used at 12 years. RESULTS: The cohort consisted of 180 children, with 90 controls. The mean IQ of the study group was 89.5 +- 16.9, which was significantly lower than that of controls (97.2 +- 14.1) (P < 0.05). The mathematical skills of the study group were significantly poorer (P < 0.05) than that of controls. A multiple linear regression analysis was done using IQ as the dependent variable and all risk factors at birth, stimulation scores and socio-environmental factors as independent variables. Mothers education was the most important factor contributing to the total IQ, a variance of 25.2 % of the total variance 44.2 PERCENT. Fathers education emerged as an important factor for mathematics skills. School was the next important factor for IQ as well as academics. Controlling for all other background factors, birth weight was the only biologic factor of significance, and this had a very small contribution. CONCLUSION: Parental education and the type of school attended by the child were the most important factors influencing cognitive development. The only biologic factor of importance was birth weight, but this too had a very small contribution.
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Peso al Nacer , Desarrollo Infantil , Cognición , Recién Nacido de Bajo Peso , Niño , Crianza del Niño , Preescolar , Estudios de Cohortes , Escolaridad , Familia , Composición Familiar , Humanos , Lactante , Recién Nacido , Pruebas de Inteligencia , Padres , Factores SocioeconómicosRESUMEN
OBJECTIVE: To assess the intelligence, visuo-motor perception, motor competence and school performance of children with birth weight less than 2000 grams, at the age of 12 years. DESIGN: Prospective cohort study. SETTING: Infants discharged from a Neonatal Special Care Unit of a referral hospital with birth weight less than 2000 g between 1987-89 and followed up in the High Risk Clinic. METHODS: The children were assessed by the Weschler's Intelligence Scale, Bender Gestalt test for visuo-motor perception, Wide Range Achievement Test for specific learning disability, Draw-a-Person screening test for emotional problems and Movement Assessment Battery for motor competence. Academic achievement was also scrutinised. RESULTS: One hundred and eighty children weighing less than 2000 grams at birth and ninety control children were assessed. The mean IQ of the study group was normal (89.5 +/- 16.9), though significantly lower than that of controls (97.2 +/- 14.1; p<0.05). Pre term SGA children had the lowest mean IQ (85.4 +/- 17.7). In the 78 VLBW children, there were 12 (15.4%) mentally retarded children as compared to only 3 (3.3%) amongst controls (p<0.001). There were only 3 (3.8%) 'bright' children among the VLBW group, as compared to 20 (22.2%) in the control group (p<0.001). Visuo-motor perception and motor competence of the study group was poor, and they had writing and mathematics learning disability, especially the preterm SGA and VLBW group. Academic achievement was poor and the incidence of borderline intelligence was 24.4%, which has increased from 13.4% at 6 years. CONCLUSIONS: The intelligence and academic performance of the children weighing less than 2000 grams is significantly lower than that of controls, though within normal limits. They also have poor visuo-motor perception, motor incompetence, reading and mathematics learning disability. The preterm SGA and VLBW children had the poorest cognitive abilities.
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Trastornos del Conocimiento/etiología , Recién Nacido de Bajo Peso , Discapacidades para el Aprendizaje/etiología , Distribución por Edad , Niño , Desarrollo Infantil/fisiología , Preescolar , Trastornos del Conocimiento/epidemiología , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Incidencia , India/epidemiología , Lactante , Recién Nacido , Pruebas de Inteligencia , Discapacidades para el Aprendizaje/epidemiología , Masculino , Pruebas Neuropsicológicas , Probabilidad , Estudios Prospectivos , Medición de Riesgo , Distribución por Sexo , Estadísticas no Paramétricas , Factores de TiempoRESUMEN
OBJECTIVE: To assess the cognitive development of non-handicapped low birth weight (LBW) infants at 18 years. DESIGN: Prospective cohort study. SETTING: Infants born between 1987 - 1989 with birth weight less than 2000 g and discharged from a neonatal special care unit were followed up till the age of 18 years. METHODS: The intelligence quotient (IQ) was determined by Ravens progressive matrices. Assessment of adjustment and aptitude was done. RESULTS: The cohort of 161 LBW infants was divided into three groups according to their gestation - preterm SGA (n=61), full term SGA (n=30) and preterm AGA (n=70). 71 full term AGA infants served as controls. The IQ of the study group (Percentile 39.3) was significantly lower than that of controls (Percentile 54.9) (P=0.002). Preterm SGA subjects had the lowest IQ (Percentile 35.5), though just within normal limits. Males from the study group had significantly lower IQ than male controls (P=0.03). The IQ of PTSGA subjects of college educated mothers (P=0.004) and belonging to higher socio-economic class (P=0.04) was significantly higher. On the differential aptitude test, PTSGA subjects were poor in speed and mechanical reasoning. The 18 year IQ could be best predicted by IQ at 6 and 12 years. CONCLUSION: Preterm SGA children have the lowest IQ at 18 years, males have lower IQ. Maternal education and socio-economic status have great impact on cognitive development. Good prediction of the 18 year IQ can be done by the 6 and 12 year IQ.
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Peso al Nacer/fisiología , Desarrollo Infantil/fisiología , Cognición/fisiología , Recién Nacido Pequeño para la Edad Gestacional/fisiología , Inteligencia/fisiología , Trastornos del Conocimiento/etiología , Femenino , Humanos , Recién Nacido , Pruebas de Inteligencia , Masculino , Estudios Prospectivos , Factores SocioeconómicosRESUMEN
OBJECTIVE: To assess the growth, adiposity and blood pressure of non-handicapped low birthweight children at 18 years. DESIGN: Prospective cohort study. SETTING: Infants born between 1987-1989 with birthweight less than 2000 g, discharged from a neonatal special care unit of a referral hospital and followed up till the age of 18 years. METHODS: The height, weight, and head circumference were measured. Measurements for adiposity, blood pressure, parental height and weight were recorded. RESULTS: The cohort of 161 low birth weight (LBW) infants was divided into three groups according to their gestation preterm SGA (n=61), full term SGA (n=30) and preterm AGA (n=70). 71 full term AGA infants served as controls. Preterm SGA males had height of 164.5 cms (162-166.9, 95% CI) which was significantly less (mean deficit = 5.7 cms) than that of controls (P=0.02). However, PTSGA children were short inspite of normal mid-parental height. Preterm SGA and AGA children had smaller head circumference. There was no evidence of adiposity and no child had hypertension. Mid-parental height was an important determinant of height in LBW children. Both parents weight and BMI were important determinants of weight and BMI, respectively in all LBW children. CONCLUSION: Preterm SGA males were short, but there was no difference in the weight of the LBW group and controls. Preterms had smaller head circumference. There was no evidence of adiposity or hypertension.