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

J Inherit Metab Dis. 2012 Sep;35(5):749-59. doi: 10.1007/s10545-011-9440-3. Epub 2012 Jan 10.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cardiomyopathies / diagnosis
  • Cardiomyopathies / genetics
  • Female
  • Fetal Growth Retardation / blood
  • Fetal Growth Retardation / diagnosis
  • Fetal Growth Retardation / genetics
  • Humans
  • Hyperammonemia / diagnosis
  • Hyperammonemia / genetics
  • Infant, Newborn
  • Infant, Premature
  • Leigh Disease / blood
  • Leigh Disease / diagnosis
  • Leigh Disease / genetics
  • Male
  • Mitochondrial Diseases / blood
  • Mitochondrial Diseases / diagnosis*
  • Mitochondrial Diseases / genetics
  • Mutation
  • Retrospective Studies