Primary Disorders of Neurotransmitter Metabolism: Experience of a Tertiary Center

Neurotransmitter diseases are a group of inherited disorders attributable to a disturbance of neurotransmitter metabolism. Biogenic amines are neurotransmitters with multiple roles including psychomotor function, hormone secretion, cardiovascular, respiratory and gastrointestinal control, sleep mechanisms, body temperature and pain. Given the multiple functions of monoamines, disorders of their metabolism comprise a wide spectrum of manifestations, with motor dysfunction being the most prominent clinical feature. Methods: Case review of 12 patients from 4 families, with primary disorders of biogenic amine metabolism. Results: Aromatic L-amino acid decarboxylase deficiency (4 patients from 2 families), and GTP-cyclohydrolase (8 patients from 2 families) were the two diseases identified. Age at first symptoms varied between 2 months and 6 years. Developmental delay was present in all cases except 2 patients with GTP cyclohydrolase deficiency. The combination of axial hypotonia and limb dystonia was also frequent. Children with aromatic L-amino acid decarboxylase deficiency exhibited temperature instability, oculogyric crisis and disturbances of sleep. The index case of one family with GTP cyclohydrolase deficiency presented with Parkinsonism (bradykinesia, rigidity and hypomimia). Analysis of neurotransmitters and their metabolites in CSF was crucial for the identification of index cases. Response to therapy was variable but in general unsatisfactory except in a family with GTP cyclohydrolase deficiency. Conclusions: These disorders should be considered in the differential diagnosis of paediatric neurodegenerative diseases, in order to allow an adequate therapeutic trial that can favor prognosis.

GM1 Gangliosidosis, Late Infantile Onset Dystonia, and T2 Hypointensity in the Globus Pallidus and Substantia Nigra

BACKGROUND: GM1 gangliosidosis is a rare disease due to mutations in the GLB1 gene and autosomal recessive deficiency of b-galactosidase. There is considerable overlap between classical phenotypes and clinical and imaging findings, which are often difficult to interpret. PATIENT: The patient in this study had dysmorphism, dysostosis, progressive dystonia, and T2 hypointensity in the basal ganglia. Partially similar clinical and radiologic findings were described previously in two reports. CONCLUSIONS: T2 hypointensity in the globus pallidus should, in the appropriate clinical setting, lead to consideration of thediagnosis of GM1 gangliosidosis.

Health-Related Quality of Life of Pediatric Intensive Care Survivors

Objetivo: Avaliar a qualidade de vida relacionada à saúde (QVRS)de crianças sobreviventes à alta da terapia intensiva pediátrica. Métodos: Foi realizada uma avaliação prospectiva da QVRS na admissão e após 6 meses em crianças com idade igual ou superior a 6 anos, internadas em três unidades de terapia intensiva pediátricas (UTIPs) terciárias de maio de 2002 a junho de 2004. A QVRS foi avaliada com o questionário Health Utilities Index Mark 3 (HUI3), aplicado a um representante da criança. Resultados: Das 517 admissões elegíveis, 44 crianças faleceram na UTIP (8,5%) e 320 casos foram avaliados na admissão; entre eles, foi possível realizar o seguimento de 252 casos. Não foram encontradas diferenças estatisticamente significativas entre os escores globais do HUI3 antes da admissão e no seguimento [medianas (intervalo interquartil) de 0,86 (0,42-1,00) e 0,83 (0,45-1,00); p = 0,674, respectivamente]. No âmbito individual, 21% das crianças não apresentaram mudanças na QVRS, foi observada melhora em 40% e agravamento em 38% dos casos. Deficiência grave antes da admissão (escore global do HUI3 < 0,70)esteve presente em 36% dos casos, com melhora no seguimento aos 6 meses em 60% deles. Entre aqueles que apresentaram agravamento da QVRS no seguimento, 45% eram vítimas de trauma. Conclusões: Embora a QVRS seja globalmente semelhante nas duas avaliações, foram encontradas várias diferenças no âmbito individual. As crianças com baixa QVRS antes da admissão (deficiência grave) podem se beneficiar da terapia intensiva pediátrica, visto que muitas dessas crianças melhoraram a QVRS, em comparação com seu estado pré-admissão.

Acute Kidney Injury after Pediatric Cardiac Surgery: Risk Factors and Outcomes. Proposal for a Predictive Model

Objectives: To characterize the epidemiology and risk factors for acute kidney injury (AKI) after pediatric cardiac surgery in our center, to determine its association with poor short-term outcomes, and to develop a logistic regression model that will predict the risk of AKI for the study population. Methods: This single-center, retrospective study included consecutive pediatric patients with congenital heart disease who underwent cardiac surgery between January 2010 and December 2012. Exclusion criteria were a history of renal disease, dialysis or renal transplantation. Results: Of the 325 patients included, median age three years (1 day---18 years), AKI occurred in 40 (12.3%) on the first postoperative day. Overall mortality was 13 (4%), nine of whom were in the AKI group. AKI was significantly associated with length of intensive care unit stay, length of mechanical ventilation and in-hospital death (p<0.01). Patients’ age and postoperative serum creatinine, blood urea nitrogen and lactate levels were included in the logistic regression model as predictor variables. The model accurately predicted AKI in this population, with a maximum combined sensitivity of 82.1% and specificity of 75.4%. Conclusions: AKI is common and is associated with poor short-term outcomes in this setting. Younger age and higher postoperative serum creatinine, blood urea nitrogen and lactate levels were powerful predictors of renal injury in this population. The proposed model could be a useful tool for risk stratification of these patients.