Questionnaire survey for the clinical outcome of the biochemically mild phenotype of IVA diagnosed by newborn screening
Carolin Wiedmann, cand. med. and Dr. Regina Ensenauer, MD
Pediatric Research Center, Dr. von Hauner Children’s Hospital, Ludwig-Maximilians-University Munich, Germany
In collaboration with Dr. Jerry Vockley, University of Pittsburgh, USA.
Background and research question: With the expansion of newborn screening approximately ten years ago, a novel form of isovaleric acidemia (IVA) that is associated with mild metabolic abnormalities and one particular recurring isovaleryl-CoA dehydrogenase (IVD) gene mutation, c.932C>T (p.A282V), was identified. This specific mutation was present (either on both copies of the IVD gene or on one copy of the IVD gene in combination with another mutation) in almost 70% of IVA patients of a newborn screening cohort. Therefore, the c.932C>T mutation was termed “common IVA mutation”. As far as we know, affected children appear to do well. However, the clinical relevance of this mild biochemical type of IVA is still entirely unclear and the question is, whether this type confers a disease risk (at any time in life) or whether it is just a benign variant. Because of this uncertainty, treatment measures seem to vary quite dramatically: from strict dietetic leucine restriction and medication with both carnitine and glycine to nearly no treatment at all.
Study method: In order to approach this problem and consequently to facilitate both treatment of affected children and guidance of their parents, we want to initiate a retrospective study. We designed a questionnaire to learn more about all children diagnosed with the metabolically mild type of IVA by newborn screening since 1999 (when expansion of newborn screening was initiated in Bavaria, Southern Germany). Patients are eligible for inclusion in the study if molecular gene analysis has shown that the c.932C>T mutation is present in one or both copies of the IVD gene. The questionnaire mainly contains questions about the type and intensity of therapeutic measures (with regards to diet and medication), the affected child’s physical and mental development, the occurrence of metabolic crises and the child’s and family’s quality of life. Questions are addressed to the parents. The parents are also asked to provide copies of the child’s medical reports including metabolic analyses of blood (isovalerylcarnitine) and urine (isovalerylglycine). Additional studies including blood draws are not required.
Aim of the study: We expect to learn about the clinical outcome of patients with the biochemically mild type of IVA, their therapeutic management and the quality of life of affected families, given the diagnosis of a chronic disease. The results of the study are expected to be used to provide management guidelines for children with the common IVA mutation for both parents and physicians. Also, we wish to improve counselling of families with a newly diagnosed baby with the biochemically mild type of IVA.
Additional information: If you would like to get more information, please feel free to contact us at Carolin.Wiedmann@med.uni-muenchen.de