Mitochondrial oxidative phosphorylation disorders presenting in neonates: clinical manifestations and enzymatic and molecular diagnoses

Pediatrics. 2008 Nov;122(5):1003-8. doi: 10.1542/peds.2007-3502.


Objectives: The goals were to examine the frequency of perinatal manifestations of mitochondrial oxidative phosphorylation disorders within a population-based cohort, to characterize these manifestations, to identify a possible association between these manifestations and diagnoses at a later age, and to identify possible associations between perinatal complications and specific disorders.

Methods: We conducted a retrospective review of clinical and laboratory records for all patients with definitive oxidative phosphorylation disorders who were diagnosed and treated at the Royal Children's Hospital in Melbourne between 1975 and 2006 (N = 107; male/female ratio: 1.41).

Results: Neonatal presentation was recorded for 32 of 107 patients (male/female ratio: 1:1), including 19 who presented on day 1 of life. Prematurity (gestational age of <37 weeks) was noted for 12.6% of the 107 patients. Of the 85 infants with known birth weights, 24 were in the <or=10th percentile for gestational age (11 with complex I deficiency), and 9 of those (6 with complex I deficiency) were in the <3rd percentile. The most common presenting neonatal symptoms after the first day of life were poor feeding, recurrent vomiting, and failure to thrive. We noted 3 main clinical neonatal forms of oxidative phosphorylation disorders (encephalomyopathic, hepatointestinal, and cardiac). Of the 32 infants, 28 died (13 in the neonatal period). Complex I deficiency was identified for 15 neonates, combined complexes I, III, and IV deficiency for 7 neonates, and combined complexes I and IV deficiency for 3 neonates. No neonates had complex IV deficiency. Six neonates had nuclear mutations, and 2 neonates had the mitochondrial DNA 8993T>G mutation.

Conclusions: Oxidative phosphorylation disorders present commonly in the neonatal period. The combination of nonspecific manifestations such as prematurity and intrauterine growth retardation with early postnatal decompensation or poor feeding or vomiting and persistent lactic acidosis should suggest the possibility of an oxidative phosphorylation disorder.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Birth Weight
  • DNA Mutational Analysis
  • Electron Transport Complex I / deficiency
  • Electron Transport Complex III / deficiency
  • Female
  • Fetal Growth Retardation / epidemiology
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Mitochondrial Diseases / diagnosis*
  • Mitochondrial Diseases / epidemiology
  • Mitochondrial Diseases / genetics
  • Mitochondrial Diseases / metabolism
  • Oxidative Phosphorylation*
  • Retrospective Studies


  • Electron Transport Complex I
  • Electron Transport Complex III