MCAD-Deficiency with Severe Neonatal Onset, Fatal Outcome and Normal Acylcarnitine Profile

Ralph Fingerhut,Susanna Sluka,Silvia Azzarello-Burri,Martin Girsberger,Niels Rupp,Pascal Joset,Anita Rauch,Theresia Herget,Matthias Baumgartner

doi:10.3390/ijns3030021

Abstract

Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is an autosomal recessively inherited disorder of fatty acid oxidation with a potentially fatal outcome in undiagnosed patients. The introduction of tandem mass spectrometry into newborn screening (NBS) has led to the inclusion of MCADD in NBS in many countries, which has resulted in a significant reduction of morbidity and mortality. We report a child with MCADD presenting neonatally with apnoea and heart arrest. Despite intensive efforts to rescue the child, including reanimation for 90 min, the child died at the second day of life. Autopsy revealed fatty liver and also fat storage in heart muscle, which was suggestive of a fatty acid oxidation defect. However, acylcarnitines determined from stored EDTA blood were not suggestive of MCADD. Nevertheless, a subsequent whole exome sequencing analysis revealed homozygosity for the ACADM gene c.1084A>G/p.Lys362Glu mutation.

Highlights

Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is the most frequent disorder of fatty acid β-oxidation
We describe a case with a fatal outcome and a normal acylcarnitine profile in an EDTA-whole blood sample, which was spotted onto filter paper after storage at 4 ◦C for 10 weeks
We report a child with MCADD presenting neonatally with sudden apnoea at the second day of life, followed by the deterioration of circulation and heart arrest

Summary

Introduction

Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is the most frequent disorder of fatty acid β-oxidation. It is an autosomal recessively inherited disorder, with a potentially fatal outcome in undiagnosed patients. The introduction of MCADD screening resulted in an at least two-fold increase of the incidence of the disorder, compared to the pre-screening era (for review see Reference [1]). The differences in genotype distribution of the pre- and post-screening era have been described by several groups [5,6,7], as well as the problem of definite confirmation of the presumptive diagnosis [8], or the prediction of the risk of metabolic decompensation in early diagnosed patients [9,10]. We describe a case with a fatal outcome and a normal acylcarnitine profile in an EDTA-whole blood sample, which was spotted onto filter paper after storage at 4 ◦C for 10 weeks

Case Report

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Discussion