Alteraciones del índice de masa corporal y peroxidación lipídica en individuos adultos con síndrome de Down / Body mass index changes and lipid peroxidation in adults with Down’s syndrome

Introducción y objetivo: La trisomía 21 o síndrome de Down (SD) es la causa más frecuente de deficiencia mental de origen cromosómico. En los pacientes afectados de SD, la obesidad es un problema de salud pública. La obesidad es un estado prooxidante, asociado con peroxidación lipídica y alteración de mecanismos antioxidantes. El efecto de dosis génica en SD se ha relacionado con estrés oxidativo. El objetivo de este estudio fue determinar el estado de peroxidación lipídica y alteraciones del índice de masa corporal (IMC) en adultos con SD. Pacientes y método: Se realizó un estudio prospectivo y transversal, en 50 adultos (31,0 ± 6,3 años) citogenéticamente normales (CN) y 29 adultos con SD (28,0 ± 8,7 años), seleccionados aleatoriamente. Se cuantificaron concentraciones séricas de malondialdehído (MDA) mediante derivados de ácido tiobarbitúrico. Asimismo, se determino el IMC en adultos con SD. El análisis estadístico requirió SPSS 15, con un intervalo de confianza del 95%, p < 0,05. Resultados: Los adultos con SD presentaron concentraciones elevadas de MDA (0,9 ± 0,7 Nmol/ml; p < 0,009) respecto al grupo de adultos CN (0,5 ± 0,4 Nmol/ml). Se observó anormalidad del IMC en el 72,4% (n = 21) de los adultos con SD. Además, se apreciaron concentraciones elevadas de MDA (1,3 ± 1,0 Nmol/ml) en adultos con SD y sobrepeso (IMC de 27,5 ± 1,3 kg/m2), y se observó una disminución no significativa en adultos obesos con SD. Conclusión: Aunque se ha reportado una reducción de enzimas antioxidantes en adultos sin SD gravemente obesos, el efecto de dosis génica podría contribuir a reducir peroxidación lipídica en adultos con SD obesos, sin representar un factor protector de sus consecuencias patológicas (AU)

Introduction and objective: Trisomy 21 or Down’s syndrome (DS) is the most common cause of mental retardation of chromosomal origin, in which obesity is a public health problem. Obesity is a pro-oxidant state associated with lipid peroxidation and alterations of antioxidant mechanisms. The effect of gene dosage has been linked to oxidative stress in DS. The objective of this study was to determine the status of lipid peroxidation and changes in body mass index (BMI) in adults with DS. Patients and method: A prospective and cross-sectional study was conducted on 50 adult subjects (31.0 ± 6.3 years) with normal karyotype (NK) and 29 adults with DS (28.0 ± 8.7 years), randomly selected. Results: The serum levels of malondialdehyde (MDA) were analysed by thiobarbituric acid derivatives. The BMI was determined in adults with DS. The data were analysed using the SPSS 15 statistical program, using a 95% confidence interval (CI), P<.05. Adults with DS showed high concentrations of MDA (0.9 ± 0.7 nmol / ml, P<.009) compared to adult NK group (0.5 ± 0.4 nmol / ml). Abnormality was observed in 72.4% of BMI (n = 21) of adults with DS. Elevated concentrations of MDA (1.3 ± 1.0 nmol / ml) were seen in adults with DS and overweight (BMI = 27.5 ± 1.3), showing no significant decrease in obese adults with DS. Conclusion: Although a reduction of antioxidant enzymes in severely obese adults without DS has been reported, the effect of gene dosage may be a contributing factor in reducing lipid peroxidation in obese adults with DS, without being a protective factor of its pathological consequences (AU)

Tripeptidil peptidasa 1 en pacientes con ceroidolipofuscinosis neuronal infantil tardía / Tripeptidyl peptidase 1 in patients with late infantile neuronal ceroid lipofuscinosis

Introducción: Las ceroidolipofuscinosis neuronales (CLN) representan un grupo de enfermedades lisosomales hereditarias de herencia autosómica recesiva, de presentación más frecuente durante la niñez, caracterizadas neuropatológicamente por acumulación de lipopigmentos autofluorescentes en los lisosomas de neuronas y otras células. Clínicamente se presentan con pérdida de las habilidades psicomotoras adquiridas, incoordinación motora, ataxia, pérdida de la visión, cambios de conducta, convulsiones de difícil tratamiento asociadas a mioclonías y una corta expectativa de vida. En la actualidad, se conocen 10 formas genéticamente distintas de esta enfermedad, entre ellas la forma infantil tardía donde las manifestaciones clínicas aparecen entre el segundo y cuarto año de vida. El gen responsable de la enfermedad es el TPP1 ubicado en 11p15 y codifica la enzima tripeptidil peptidasa 1. Pacientes y métodos: Se estandarizó la técnica para el diagnóstico enzimático de la ceroidolipofuscinosis neuronal infantil tardía a través de sangre seca en papel de filtro en 76 individuos sanos en edad preescolar y adulta de población venezolana. La actividad enzimática de la TPP1 fue determinada en 9 pacientes con diagnóstico clínico de ceroidolipofuscinosis infantil tardía 2 (CLN2). Resultados: Seis pacientes mostraron valores de actividad muy por debajo del rango establecido (0,11-0,45 nmol/mancha) para los controles sanos en edad preescolar, confirmando el diagnostico enzimático. Tres de los 14 padres estudiados presentaron valores en el rango de heterocigotos. Conclusiones: El diagnóstico enzimático de CLN2 a través de la determinación de la actividad enzimática de la enzima TPP1 mediante la técnica de sangre seca en papel de filtro permite un diagnóstico rápido, sencillo, económico y confiable(AU)

Introduction: Neuronal ceroid lipofuscinoses are a group of inherited autosomal recessive lysosomal diseases, most commonly found in infancy. These are neuropathologically characterised by accumulation of an autofluorescent lipopigment in neurons and other cells. This condition is clinically characterised by loss of motor and cognitive skills, lack of motor coordination, ataxia, progressive visual impairment, behavioural changes; seizures of difficult to manage seizures, particularly myoclonic, and premature death. Ten clinical forms have been described, one of which is late infantile where clinical signs begin between two and four years. The gene responsible for this disease is located at 11p15 locus, and the enzyme encoded by this gene is the tripeptidyl peptidase 1. Patients and methods: We standardised the technique for the enzymatic diagnosis of late infantile neuronal ceroid lipofuscinoses from dried blood on filter paper card in 76 healthy individuals adults and children in order to establish a normal range in the Venezuelan population. The tripeptidyl peptidase activity was also determined in 9 patients with a clinical diagnosis of late infantile neuronal ceroid lipofuscinoses. Results: Six of the samples showed activity lower than the lowest control value (0.11 to 0.45 nmol/spot) from healthy controls of infantile age, confirming the enzymatic diagnosis. Three of the 14 parent samples analysed showed values in the heterozygote ranges. Conclusions: The enzymatic diagnosis of late infantile neuronal ceroid lipofuscinoses from dried blood on filter paper card is a rapid, easier, less expensive and accurate molecular diagnosis tool(AU)

[Tripeptidyl peptidase 1 in patients with late infantile neuronal ceroid lipofuscinosis]. / Tripeptidil peptidasa 1 en pacientes con ceroidolipofuscinosis neuronal infantil tardía.

INTRODUCTION: Neuronal ceroid lipofuscinoses are a group of inherited autosomal recessive lysosomal diseases, most commonly found in infancy. These are neuropathologically characterised by accumulation of an autofluorescent lipopigment in neurons and other cells. This condition is clinically characterised by loss of motor and cognitive skills, lack of motor coordination, ataxia, progressive visual impairment, behavioural changes; seizures of difficult to manage seizures, particularly myoclonic, and premature death. Ten clinical forms have been described, one of which is late infantile where clinical signs begin between two and four years. The gene responsible for this disease is located at 11p15 locus, and the enzyme encoded by this gene is the tripeptidyl peptidase 1. PATIENTS AND METHODS: We standardised the technique for the enzymatic diagnosis of late infantile neuronal ceroid lipofuscinoses from dried blood on filter paper card in 76 healthy individuals adults and children in order to establish a normal range in the Venezuelan population. The tripeptidyl peptidase activity was also determined in 9 patients with a clinical diagnosis of late infantile neuronal ceroid lipofuscinoses. RESULTS: Six of the samples showed activity lower than the lowest control value (0.11 to 0.45 nmol/spot) from healthy controls of infantile age, confirming the enzymatic diagnosis. Three of the 14 parent samples analysed showed values in the heterozygote ranges. CONCLUSIONS: The enzymatic diagnosis of late infantile neuronal ceroid lipofuscinoses from dried blood on filter paper card is a rapid, easier, less expensive and accurate molecular diagnosis tool.

Deficiencia de vitamina A y estado nutricional en pacientes con Síndrome de Down / Vitamin A deficiency and nutritional status in patients with Down's syndrome

Introducción: La deficiencia de vitamina A (DVA) constituye un problema de salud pública a nivel mundial. Estudios epidemiológicos de prevalencia de DVA se han realizado en individuos con carga cromosómica y potencial genético acorde con la población general; no obstante, son escasos los estudios en pacientes con síndrome de Down (SD). El objetivo fue determinar la prevalencia de DVA y estado nutricional en pacientes con SD. Métodos: Se realizó un estudio prospectivo y transversal, en 50 controles (10,4±3,7 años) citogenéticamente normales (CN) y 38 pacientes con SD (8,2±4,1 años), seleccionados aleatoriamente. Se determinó retinol sérico por HPLC según el método de Bieri, utilizando valores de referencia internacional que definen DVA <20μg/dl. Se aplicó el programa SAS/STAT para el análisis estadístico. Resultados: La prevalencia de DVA en pacientes con SD fue 18,4% y en controles CN 4% (OR: 5,64; IC 95%=1,10–28,93; p=0,03). Los niños con SD entre 2–6 años mostraron una reducción significativa de los valores de retinol sérico (p=<0,05). La talla y el peso en pacientes con SD se observó significativamente por debajo de individuos CN (p=<0,001). Conclusión: La alta prevalencia de DVA en individuos con SD debe ser considerada un problema de salud pública. De este modo, la trisomía del cromosoma 21 constituye un factor de riesgo asociado a DVA (AU)

Introduction: Vitamin A deficiency (VAD) is a worldwide public health problem. Epidemiological studies of VAD prevalence have been conducted in individuals with chromosome load and genetic potential compared with the general population; however, there are few studies in patients with Down's syndrome (DS). The objective of this study was to determine the prevalence of VAD and analyse nutritional status in patients with DS. Methods: A prospective and cross-sectional study was performed, with 50 karyotypically normal (KN) individuals (10.4±3.7 years old) and 38 randomly selected patients with DS (8.2±4.1 years old). Serum retinol was determined by HPLC using the Bieri method, with an international reference standard to define VAD (serum retinol <20μg/dL). The data were analysed using the SAS/STAT statistical program. Results: The prevalence of VAD was 18.4% in individuals with DS and 4% in KN individuals (OR: 5.42; 95% CI=0.93–40.64; p=0.02). Children with DS between two and six years old shown a significativily lower serum retinol (p=<0.05).The patients with DS also showed a significant decrease in height and weight compared to KN (p=<0.001). Conclusions: The prevalence of VAD detected in patients with DS could be considered a public health problem. Also, the chromosome 21 trisomy represent a risk factor associated with VAD (AU)

[Vitamin A deficiency and nutritional status in patients with Down's syndrome]. / Deficiencia de vitamina A y estado nutricional en pacientes con Síndrome de Down.

INTRODUCTION: Vitamin A deficiency (VAD) is a worldwide public health problem. Epidemiological studies of VAD prevalence have been conducted in individuals with chromosome load and genetic potential compared with the general population; however, there are few studies in patients with Down's syndrome (DS). The objective of this study was to determine the prevalence of VAD and analyse nutritional status in patients with DS. METHODS: A prospective and cross-sectional study was performed, with 50 karyotypically normal (KN) individuals (10.4+/-3.7 years old) and 38 randomly selected patients with DS (8.2+/-4.1 years old). Serum retinol was determined by HPLC using the Bieri method, with an international reference standard to define VAD (serum retinol <20 microg/dL). The data were analysed using the SAS/STAT statistical program. RESULTS: The prevalence of VAD was 18.4% in individuals with DS and 4% in KN individuals (OR: 5.42; 95% CI=0.93-40.64; p=0.02). Children with DS between two and six years old shown a significativily lower serum retinol (p=<0.05).The patients with DS also showed a significant decrease in height and weight compared to KN (p=<0.001). CONCLUSIONS: The prevalence of VAD detected in patients with DS could be considered a public health problem. Also, the chromosome 21 trisomy represent a risk factor associated with VAD.

Children of methadone-treated women at five years of age.

Infants of methadone-treated and matched non-drug dependent women were found to differ in psychomotor development at one year of age. A follow-up of these groups at age five revealed no differences in cognitive or perceptual performance as assessed by the McCarthy Scales, although both groups performed below normative expectations. Groups did not differ in observed characteristics of home environments or patterns of child or caregiver behavior in a playroom observation, although children who had been transplacentally exposed to narcotics behaved less maturely and were more inappropriately active during psychological testing.

Behavioural concomitants of prenatal addiction to narcotics.

Behavioral characteristics of infants of methadone-treated and nonaddicted women were studied during the neonatal period and at three, six, and 12 months of age. Several Brazelton Neonatal Behavioral Assment Scale measures differentiated between groups. Major differences occurred in irritability of the central nervous system, and these measures appeared able to predict severity of withdrawal. The increased tremulousness of addicted infants remained through at least the first month of life. Mental and motor development was within normal limits in both groups throughout the year. However, the addicted infants showed a progressive decline in psychomotor performance whereas nonaddicted infants' scores remained stable.

A study of factors that influence the severity of neonatal narcotic withdrawal.

A prospective study of 196 drug-addicted mothers and their infants was conducted to determine the maternal, fetal, or environmental factors that may affect the severity of narcotic withdrawal in the infants. The severity of neonatal withdrawal did not correlate with the infant's gestational age, sex, race, or Apgar score, not to maternal age, parity, duration of heroin intake, or the level of morphine measured in the infant's urine or blood. Reduction in the amount of illumination and noise in a study nursery also did not lower the incidence of severe withdrawal in the infants. There was, however, significant correlation between the severity of withdrawal in the infant and the maternal methadone dose (p less than 0.025). It is therefore recommended that mothers on methadone treatment be put on a low dose of the drug (less than 20 mg/day) as soon as is safely possible to prevent serious withdrawal in her infant.

A study of factors that influence the severity of neonatal narcotic withdrawal.

1. History is unreliable in assessing maternal drug habit. Morphine was detected in significant amounts in maternal and fetal urine regardless of whether the mother was on a methadone program or whether she denied any use of heroin during the last trimester of pregnancy. 2. Infants born to drug-addicted mothers were, in general, of birthweight normal and appropriate for gestational age (i.e., greater that 10th percentile). The infants born to mothers on a methadone clinic program had a higher birthweight compared to those whose mothers were not on any methadone program. 3. In order of frequency, the signs and symptoms of withdrawal were: central nervous system manifestations-fist sucking, irritability, tremors, sneezing, high-pitch cry, hypertonia; vasomotor in the form of stuffy nose; and gastrointestinal in the form of sweating, diarrhea, vomiting and yawning. Convulsions were not noted. No death occurred. 4. The severity of neonatal narcotic withdrawal did not correlate with the infant's gestational age, APGAR, sex or race; nor with maternal age, parity, duration of heroin addiction or duration of methadone intake. Also, it did not correlate with the total morphine level measured either in infant's or mother's urine or in cord blood. The serum levels of calcium and glucose were normal and identical in either mild or severe withdrawal. 5. The severity of neonatal withdrawal correlated significantly with the methadone dose per day of the mother (in initial, final or average dose). A maternal methadone dose of more than 20 mg per day was associated with a higher incidence of moderate to severe withdrawal in their babies. As a corollary, it was also noted that infants whose mothers were on a high methadone dose (i.e., greater than 20 mg per day) had a greater postnatal weight loss despite a significantly higher birthweight initially, and stayed in the hospital longer. 6. Finally, the modification of the environment to reduce external stimuli to the infant born to a drug-dependent mother, does not prevent or diminish the severity of neonatal narcotic withdrawal. Thus, there is no need to manage these infants in a special nursery.