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


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.


CONCLUSIONS
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.
Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Ke Karlovu 2, 120 00, Prague 2, Czech Republic.
Tomas
T
Honzik
Marketa
M
Tesarova
Martin
M
Magner
Johannes
J
Mayr
Pavel
P
Jesina
Katerina
K
Vesela
Laszlo
L
Wenchich
Karol
K
Szentivanyi
Hana
H
Hansikova
Wolfgang
W
Sperl
Jiri
J
Zeman
D009202:Cardiomyopathies / Q000175:diagnosis / Q000235:genetics; D005260:Female; D005317:Fetal Growth Retardation / Q000097:blood / Q000175:diagnosis / Q000235:genetics; D006801:Humans; D022124:Hyperammonemia / Q000175:diagnosis / Q000235:genetics; D007231:Infant, Newborn; D007234:Infant, Premature; D007888:Leigh Disease / Q000097:blood / Q000175:diagnosis / Q000235:genetics; D008297:Male; D028361:Mitochondrial Diseases / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D009154:Mutation; D012189:Retrospective Studies