The natural course of MADD in the Netherlands.

Rijt, W.J. van (2015) The natural course of MADD in the Netherlands. thesis, Medicine.

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Abstract

Objectives: To study the natural course of Multiple Acyl-CoA Dehydrogenase Deficiency (MADD) in the Netherlands and to provide a clear assessment whether it would be acceptable to include MADD in the population newborn screening (NBS) program. Methods: A national, retrospective cohort study of the clinical, biochemical, molecular and follow-up data of all Dutch MADD-patients (n=28). Data was collected by examining the (electronic and/or paper) medical files. The cohort was subsequently described and the biochemical profiles were statistically analyzed using Mann Whitney U tests and Kruskal Wallis tests. Differences were considered significant at p<0.05. Results: From the 28 diagnosed MADD-patients, 2 displayed type I, 5 type II and 13 type III MADD, amongst whom 2, 3, and 1 patients died, respectively. The 8 remaining patients could not be classified as they have remained asymptomatic after diagnosis through positive screening results and/or have been treated since the first day of life. In total, 17 patients suffered from one or multiple acute presentations. Chronic symptoms were reported in 6 patients, of whom 2 also experienced acute episodes. Molecular studies demonstrated 13 pathogenic mutations in 12 families, including 6 novel MADD-mutations: ETF-β: c.187G>A; ETF-DH: c.881C>T, c.1118C>T, c.1768A>T, c.1842C>A and IVS5 + 1G>A. Several plasma acylcarnitines upon diagnosis, including the sum of short chain acylcarnitines C4-C6, the sum of long chain acylcarnitines C14-C18 and the following acylcarnitines: C4, C5, C12:1, C14, C16:1, C16, C18:1 and C18, could be significantly related to MADD-type. Furthermore, the GA-II index could be significantly related to MADD-type and it might be a possible biochemical marker for follow-up. Conclusions: MADD is a phenotypically (clinically, biochemically) and genetically heterogeneous disease. Clinical outcome ranges from death during the neonatal period to remaining asymptomatic throughout life. MADD should not yet be included in the NBS program as various criteria of population neonatal screening are not met. More research should be performed concerning the genotype-phenotype relation, diagnostic methods and treatment options to be able to fulfil the principles for population neonatal screening in order for MADD to be implemented in the NBS program.

Item Type:	Thesis (Thesis)
Supervisor name:	Derks, T.G.J.
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 11:00
Last Modified:	25 Jun 2020 11:00
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/2022

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