Expanded Newborn Screening and Genomic Sequencing in Latin America and the Resulting Social Justice and Ethical Considerations.

Newborn screening (NBS) has widely been utilized in developed countries as a cost-effective public health strategy that reduces morbidity and mortality. Developing countries, however, are new to the NBS scene and have their own unique challenges, both in instituting the program as well as effectively acting on the results. NBS offers numerous ethical issues on a global scale, however, here we argue that there are unique ethical issues surrounding the development and expansion of newborn screening in Latin America given its highly heterogenous population. Once a NBS program is effectively instated, ethical considerations continue when pursuing expansion of screening to include further conditions. While Latin America grapples with the ethics of expanded newborn screening (ENBS), some developed countries discuss utility of genomic sequencing technologies in the newborn population. When the ability to detect further pathology is expanded, one must know what to do with this information. As rare diseases are identified either on ENBS or via genome sequencing, access to treatments for these rare diseases can be a real challenge. If we consider newborn screening as a global initiative, then we need more than a deontology approach to analyze these challenges; we need an approach that considers the unique characteristics of each territory and tremendous heterogeneity that exists prior to the implementation of these programs. As genomic technology advances further in the developed world, while some developing countries still lack even basic newborn screening, there is a further widening of the gap in global health disparities. The question is posed as to who has responsibility for these newborns' lives on an international level. Without an approach towards newborn screening that accounts for the diverse global population, we believe optimal outcomes for newborns and families across the world will not be achieved.

Efectos de la prematurez sobre el desarrollo cognitivo y la atención en etapa escolar / Effects of prematurity on cognitive development and attention at school age

Gracias a los avances tecnológicos, los niños prematuros con discapacidades físicas mayores han disminuido su prevalencia; actualmente, los defectos cognitivos son la secuela predominante. Se investigó el desarrollo cognitivo y la atención en escolares con antecedentes de haber sido recién nacidos prematuros, a través de un estudio descriptivo, de corte transversal, en que se realizaron evaluaciones neuropsicológicas mediante WISC-R y test de Gordon a niños escolares con antecedentes de prematurez (EG<33s y/o PN<1500g) y niños controles con antecedentes de ser recién nacidos de término. Se evaluó a 77 pacientes: 40 niños prematuros (EG: 30,5 s) y 37 de término, entre 6-7 años. Aunque ambos grupos obtuvieron un CIT dentro del rango normal, se observó diferencias significativas (p<0,03) en desmedro del grupo prematuro en comparación con controles. Las habilidades atencionales también fueron significativamente menores para los prematuros (p< 0,01). Los niños prematuros se encuentran en riesgo de presentar problemas cognitivos y/o de atención en la etapa escolar. Se sugiere incorporar instrumentos de pesquisa de estas dificultades durante el seguimiento, que permitan un reconocimiento precoz e intervención oportuna.

The prevalence of premature children with major physical disabilities has diminished over time mainly due to advances in technology. Cognitive disorders are currently the main sequels. In order to study cognitive and attentional functioning of extremely premature infants at school age, a cross sectional study was designed. Neuropsychological assessments were performed by WISC-R and Gordon test, in prematures and controls at school age. Seventy seven children, 40 preterm (GA: 30.5 w) and 37 term at birth, aged 6-7 years-old were assessed. Although both groups obtained an overall IQ within the normal range, prematures showed significantly lower scores than the control group (p< 0.03). Attentional skills were also significantly lower (p <0.01) in the premature children. Children with a history of extreme prematurity are at risk for cognitive and attention impairment at school age. We suggest to introduce screening tools during follow-up which allow early recognition and appropriate intervention.

Perfil epidemiológico do trauma dentário e facial em Curitiba / Epidemiological profile of dental and facial trauma in Curitiba

Introdução: Trauma é uma lesão produzida por ação violenta, em geral de natureza física externa ao organismo.O atendimento é de urgência e alta complexidade. O trauma, além de sequelas físicas, traz também sequelas psicológicas graves. Os traumas faciais e dentários causam grandes conflitos psicológicos em virtude do comprometimento da estética. Objetivos: Analisar o perfil epidemiológico do trauma dentofacial nos pacientes atendidos no ano de 2009, no Pronto-Socorro Geral e Odontológico do Hospital Universitário Cajuru, na cidade de Curitiba (PR). Materiais e métodos: O estudo foi realizado por meio da análise retrospectiva de 1.380 prontuários de pacientes vítimas de trauma dentofacial atendidos no Hospital Universitário Cajuru no ano de 2009. Resultados: O sexo masculino compreendeu 66,37% dos pacientes traumatizados.A faixa etária de zero aos 10 anos foi a mais afetada, com 38,47%. As quedas foram o principal motivo dos traumas (53,92%). Os domingos (17,39%) e o período noturno (35,90%) foram os momentos mais frequentes dos traumatismos. O trauma dentário mais frequente foi a fratura coronária (30,25%) e os dentes mais acometidos foram os incisivos centrais (45,64%) Conclusão: As crianças foram as principais vítimas.O sexo masculino foi o mais acometido. Os traumas ocorrem, em sua maioria, durante a noite, sendo que no domingo a ocorrência desse tipo de trauma foi maior. A etiologia da maioria dos traumas são as quedas.O trauma dentário mais frequente foi a fratura coronária sendo que os dentes incisivos centrais são os mais frequentemente afetados. A maioria dos pacientes não sofreu fraturas ósseas associadas.

Introduction: Trauma is a lesion produced by a violent action, usually from outside the body. The service isurgent and of high complexity. The facial trauma brings high physiological conflict due to the impairment ofaesthetics. Objectives: The aim of the study was to analyze the epidemiological profile of dentofacial traumaof patients treated during the year 2009 in the Dental Emergency Service of the Cajuru Hospital, located inthe city of Curitiba (PR, Brazil). Materials and methods: The study was carried out through the retrospectiveanalysis of 1,380 medical records of patients victims of dentofacial trauma taken care in CajuruHospital duringthe year of 2009. Results: It was observed that 66,37% from the affected patients were men. Children (0 to 10years old) were the most affected age group, with 38,47%. The falls were the main cause of traumas (53,92%).Sundays (17,39%) and the nighttime (35,90%) were the most frequentperiod of time that traumas occurred.The most frequent type of trauma was the coronary fracture (30,25%) and the most affected teeth were centralincisors (45,64%). Conclusions: The children were the main victims of dentofacial trauma. The male sex wasthe most affected. It was noticed that traumas occur mostly during the night and on Sundays. The most frequentlyreported etiology of trauma was fall. The coronal fracture was the most frequent type of fracture andthe central incisor was the most affected tooth. Most of the patients did notreport associated bone fractures.

[Glucose transponer type 1 deficiency síndrome (GLUT-1 SD) treated with ketogenic diet. Report of one case]. / Síndrome de deficiencia del transportador de glucosa tipo 1 (SDGLUT-1) tratado con dieta cetogénica. Caso clínico.

The glucose transporter type 1 deficiency syndrome (GLUT-1 SD) (OMIM 606777) is an inborn error of metabolism of brain glucose transport. The characteristic clinical manifestations are seizures, hypotonia, developmental delay, microcephaly and hypoglycorrhachia. We report a girl with normal weight and height at birth. At 6 weeks of age she started with convulsions reaching up to 20 myoclonic seizures a day. She was treated with valproate, phenobarbital and carbamazepine without response. Blood analysis including aminoacids and acylcarnitines were all normal. The brain MRI showed frontal atrophy with an increased subarachnoidal space and Electroencephalography was abnormal. Blood glucose was 84 mg/dl and spinal fluid glucose 26 mg/dl with a ratio of 0.31 (Normal Ratio >0.65+/-00.1). These results suggested the diagnosis of GLUT-1 SD, and was confirmed with erythrocyte glucose uptake of 44% (Normal range 80-100%). A molecular study found the mutation 969del, C971T in exon 6 of the gene Glut-1. Treatment with a ketogenic diet was started immediately and after 7 days with this diet seizures ceased. Anticonvulsants were progressively suspended. At present, the patient is 6 years old, she continues on a ketogenic diet and supplements with L-carnitine, lipoic acid, vitamins and minerals. Growth and development are normal with an intelligence quotient of 103. It is concluded that it is necessary to include GLUT-1 SD in the differential diagnosis of children with early seizures that are non responsive to pharmacological treatment.

[Phenylketonuria diagnosed during the neonatal period and breast feeding]. / Fenilquetonuria de diagnóstico neonatal y lactancia materna.

BACKGROUND: Phenylketonuria (PKU) is due to of a defect in the phenylalanine hydroxylase gene (12q22-24.1) leading to hyperphenylalaninemia. Treatment consists in a low phenylalanine (Phe) diet. AIM: To evaluate the evolution of early diagnosed PKU children, receiving direct breast feeding, and a special formula without Phe, during their first six months of life. PATIENTS AND METHODS: Nineteen PKU children diagnosed in the neonatal period (19.29 +/- 13.8 days of age), treated with breast feeding and formula without Phe since diagnosis, were studied. Intake of calories, proteins and dietary Phe were quantified. Blood Phe, nutritional status and psychomotor development were also measured. RESULTS: The diet that these children received during the 6 months period of study, had a mean of 127 +/- 19.9 Kcal/kg/day, 1.95 +/- 0.3 g protein/kg/day and 35.3 +/- 9.5 mg Phe/kg/day. Fifteen children maintained the blood level of Phe under 8 mg/dl, considered an excellent metabolic control. Only 4 cases had intermittently high levels, between 10-12 mg/dl. At 6 months of age, 74% of the children maintained breast feeding as the only source of Phe. Sixty three percent had a normal nutritional status, 5.2% were at nutritional risk and 31.6% were overweight. Eighty one percent had a normal mental development. CONCLUSIONS: The use of direct breast feeding allows a good metabolic control and improves growth and development of early diagnosed PKU children.

[Diagnosis and follow up of 23 children with organic acidurias]. / Diagnóstico y seguimiento de 23 niños con acidurias orgánicas.

BACKGROUND: Propionic aciduria (PA) and Methymalonic aciduria (MMA) result from an inherited abnormality of the enzymes propionyl CoA carboxylase and methylmalonyl CoA mutase respectively. This produces marked increases in the amino acids methionine, threonine, valine and isoleucine (MTVI). Their clinical presentation can be neonatal or late onset forms. AIM: To report 23 children with organic acidurias. MATERIAL AND METHODS: Twenty three cases of organic acidurias diagnosed since 1980 (17 PA and 6 MMA) and followed at the Institute of Nutrition and Food Technology, are reported. RESULTS: The average age of diagnosis was 3.9 days for the neonatal form and 8.3 months for the late onset form. The most frequent symptoms were hypotonia, lethargy and vomiting. Neonatal PA had mean ammonemias of 1089 +/- 678.3 micrograms/dl. The figure for MMA was 933 +/- 801.9 micrograms/dl. Seven children were dialyzed and 30% died. 16 children are followed and 81.2% have normal weight for age. Seven children required gastrostomy because of anorexia and failure to thrive. The nutritional treatment is based on natural and artificial proteins without MTVI, with periodical controls, amino acid and ammonia quantification. Some patients were submitted to enzyme assays and molecular studies. CONCLUSIONS: An early diagnosis and a very strict follow up allows a normal development of children with organic acidurias. There is a relationship between prognosis and the presentation form, the nutritional status and the emergency treatment during acute episodes. The importance of the enzymatic and molecular studies is emphasized because they facilitate treatment, accurate diagnosis and allow an adequate genetic counseling.

Estudio de funciones cognitivas en escolares de nivel intelectual normal con antecedentes de desnutrición grave y precoz / A study on the cognitive functions of school children with normal IQ and histories of severe and early malnutrition

El presente trabajo es un estudio de corte transversal, cuyo objetivo fue evaluar los efectos a largo plazo de la desnutrición calórica-proteica severa y precoz sobre el desarrollo de funciones cognitivas básicas. La atención, memoria y capacidad de resolver problemas fue comparada entre un grupo de 16 escolares, con antecedentes de desnutrición marásmica severa durante los dos primeros años de vida y 16 escolares con un crecimiento normal. Todos los sujetos presentaban un coeficiente intelectual normal, una edad entre 8-10 años y pertenecían al mismo nivel socieconómico. Las funciones cognitivas fueron evaluadas empleando un microcomputador. La memoria se midió mediante una modificación de la subprueba de digitos del WISC; la atención con una modificación del Continous Perfomance Task y la capacidad de resolver problemas con una adaptación de la prueba de Dominó de Anstey. El grupo con atecedentes de desnutrición presentó un rendimiento menor que el grupo control, en las mediciones de memoria (Nº de dígitos retenidos) y en la capacidad de resolver problemas (Nº de respuestas correctas). En la prueba de atención, el grupo con antecedentes de desnutrición obtuvo un rendimiento interior en la latencia de respuesta frente a las respuestas correctas. Se concluye que estas diferencias sugieren que la desnutrición temprana tendría efectos deletéreos sobre funciones cognitivas básicas

Desnutrición grave precoz y desarrollo psicomotor. Efectos de un programa de rehabilitación / Early severe malnutrition and psychomotor development. Effects of a rehabilitation program

This study evaluates the psychomotor development of 228 undernourished infants submitted to an integral rehabilitation program in Nutritional Recovery Centers. At admission these children present a moderate retardation of their developmental quotient: mean 0.59 +/- 0.17, improving significantly to mean 0.79 +/- 0.4 (p < 0.001) after an average period of 178.2 +/- 63.9 days of intervention. As regards areas of development, rehabilitation only demonstrates a significant change in coordination and language, not so in the social and motor areas. Those children presenting the most severe developmental delays are also those who obtain the greater benefits from this integral rehabilitation program.

Diagnóstico de fenilquetonuria en Chile / Phenylketonuria: late diagnosis

Se presentan las características clínicas y bioquímicas de 4 niños PKU diagnosticados tardíamente, a una edad promedio de 3 años 11 meses. Se enfatiza la importancia de hacer un diagnóstico y tratamiento oportuno, de modo de prevenir la aparición de retardo mental. Se plantea la necesidad de desarrollar un programa de búsqueda masiva para la detección de PKU en el período neonatal en nuestro país

Enfermedad de Lesch-Nyhan / Lesch-Nyhan disease

Se presenta un caso de Enfermedad de Lesch-Nyhan típico, cuyo diagnóstico fue confirmado a través de técnicas de crecimiento celular diferencial. Esta técnica permitió también establecer la condición de portadora en la madre y una de las tías en la que se realizó el diagnóstico prenatal de un nuevo caso. Se revisan algunos aspectos clínicos, metabólicos y terapéuticos de interés, enfatizando la importancia de los estudios diagnósticos específicos para el consejo genético adecuado de familias con esta rara pero grave enfermedad