Neurodevelopmental outcomes of children with inherited metabolic disorders

© 2014 Dr. Amy BrownIntroduction: Inherited metabolic disorders (IMD) are caused by mutations that lead to deficiencies in enzymes or defects in transporters, channels or receptors etc. As a result there is a block in metabolic pathways, triggering toxicities and deficiencies that affect various organs. Their effect on the developing brain has the potential to disrupt neurodevelopment in childhood, and therefore impact upon cognition, behaviour and social skills. Background: An evaluation of the existing literature revealed that I comparison to research on Phenylketonuria, there was a lack of detailed research on neurodevelopmental outcomes of children with other IMD, especially in children diagnosed through newborn screening. More specifically, very few publications include follow up data, did not utilise standardised comprehensive measures and did not consider other environmental factors that may impact on outcomes. A distinct gap was evident in regards to social functioning in children. Aims: The aims of this thesis were (1) to investigate the neurodevelopmental outcomes of children with several inherited metabolic disorders; (2) to explore the impact of having a child with an IMD on parents and how this may affect child outcomes. Method: Children with a confirmed diagnosis of one of the following disorders; glutaric aciduria type I, maple syrup urine disorder, methylmalonic aciduria, propionic aciduria, isovaleric aciduria, glycogen storage disease, very long chain acyl-CoA dehydrogenase deficiency and ornithine transcarbamylase deficiency and their parents were invited to participate in the study. These disorders were targeted to represent a range of disorders (i.e, amino acid, carbohydrate, and fatty acid oxidation disorders) and based on the availability of patients within the hospital. Children underwent a neuropsychological assessment and parents completed questionnaires regarding their behaviour and social skills. Some parents completed questionnaires regarding their own coping, psychological distress and family management. Results: The children in the glutaric aciduria type I follow-up study (all diagnosed through newborn screening) generally showed no evidence of decline in cognitive functioning, however all had impaired fine motor skills and some had problems with speech or language. Children with very long chain acyl-CoA dehydrogenase deficiency diagnosed through newborn screening had mostly normal motor and cognitive functioning, with some evidence for speech or language problems. As a cross sectional group, children demonstrated intact social perception and parents reported mostly average social skills, although some children were experiencing peer problems, hyperactivity and emotional symptoms. On reports of their own functioning, parents reported adequate coping although a small subset of parents reported at risk levels of psychological distress. Parent coping and family functioning were related to some child behaviour and social outcomes. Conclusion: Children with inherited metabolic disorders may be vulnerable to neurodevelopmental problems despite mode of diagnosis. Neuropsychological assessment is recommended and referrals made where necessary. Further consideration should be given to the child’s environment (parent stress and coping, family functioning) and how this may impact their outcomes.