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Journal of Inherited Metabolic Disease
Published in: Journal of Inherited Metabolic Disease 5/2012

01-09-2012 | Original Article

Neonatal onset of mitochondrial disorders in 129 patients: clinical and laboratory characteristics and a new approach to diagnosis

Authors: Tomas Honzik, Marketa Tesarova, Martin Magner, Johannes Mayr, Pavel Jesina, Katerina Vesela, Laszlo Wenchich, Karol Szentivanyi, Hana Hansikova, Wolfgang Sperl, Jiri Zeman

Published in: Journal of Inherited Metabolic Disease | Issue 5/2012

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Abstract

Introduction

Mitochondrial disorders (MD) may manifest in neonates, but early diagnosis is difficult. In this study, clinical and laboratory data were analyzed in 129 patients with neonatal onset of MD to identify any association between specific mitochondrial diseases and their symptoms with the aim of optimizing diagnosis.

Materials and methods

Retrospective clinical and laboratory data were evaluated in 461 patients (331 families) with confirmed MD.

Results

The neonatal onset of MD was reported in 28% of the patients. Prematurity, intrauterine growth retardation and hypotonia necessitating ventilatory support were present in one-third, cardiomyopathy in 40%, neonatal seizures in 16%, Leigh syndrome in 15%, and elevated lactate level in 87%. Hyperammonemia was observed in 22 out of 52 neonates. Complex I deficiency was identified in 15, complex III in one, complex IV in 23, complex V in 31, combined deficiency of several complexes in 53, and PDH complex deficiency was identified in six patients. Molecular diagnosis was confirmed in 49 cases, including a newborn with a 9134A>G mutation in the MTATP6 gene, which has not been described previously.

Conclusion

The most significant finding is the high incidence of neonatal cardiomyopathy and hyperammonemia. Based on our experience, we propose a diagnostic flowchart applicable to critically ill neonates suspicious for MD. This tool will allow for the use of direct molecular genetic analyses without the need for muscle biopsies in neonates with Alpers, Barth, MILS and Pearson syndromes, SCO1, SCO2, TMEM70, ATP5E, SUCLG1 gene mutations and PDH complex deficiency.
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Metadata
Title
Neonatal onset of mitochondrial disorders in 129 patients: clinical and laboratory characteristics and a new approach to diagnosis
Authors
Tomas Honzik
Marketa Tesarova
Martin Magner
Johannes Mayr
Pavel Jesina
Katerina Vesela
Laszlo Wenchich
Karol Szentivanyi
Hana Hansikova
Wolfgang Sperl
Jiri Zeman
Publication date
01-09-2012
Publisher
Springer Netherlands
Published in
Journal of Inherited Metabolic Disease / Issue 5/2012
Print ISSN: 0141-8955
Electronic ISSN: 1573-2665
DOI
https://doi.org/10.1007/s10545-011-9440-3

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