Long-term outcome and clinical spectrum of 73 pediatric patients with mitochondrial diseases

Pediatrics. 2007 Apr;119(4):722-33. doi: 10.1542/peds.2006-1866.


Objectives: We sought to determine the clinical spectrum, survival, and long-term functional outcome of a cohort of pediatric patients with mitochondrial diseases and to identify prognostic factors.

Methods: Medical charts were reviewed for 73 children diagnosed between 1985 and 2005. The functional status of living patients was assessed prospectively by using the standardized Functional Independence Measure scales.

Results: Patients fell into 7 phenotypic categories: neonatal-onset lactic acidosis (10%), Leigh syndrome (18%), nonspecific encephalopathy (32%), mitochondrial (encephalo)myopathy (19%), intermittent neurologic (5%), visceral (11%), and Leber hereditary optic neuropathy (5%). Age at first symptoms ranged from prenatal to 16 years (median: 7 months). Neurologic symptoms were the most common (90%). Visceral involvement was observed in 29% of the patients. A biochemical or molecular diagnosis was identified for 81% of the patients as follows: deficiency of complex IV (27%), of pyruvate dehydrogenase or complex I (25% each), of multiple complexes (13%), and of pyruvate carboxylase (5%) or complexes II+III (5%). A mitochondrial DNA mutation was found in 20% of patients. At present, 46% of patients have died (median age: 13 months), 80% of whom were <3 years of age. Multivariate analysis showed that age at first symptoms was a major independent predictor of mortality: patients with first symptoms before 6 months had a highly increased risk of mortality. Cardiac or visceral involvement and neurologic crises were not independent prognostic factors. Living patients showed a wide range of independence levels that correlated positively with age at first symptoms. Among patients aged >5 years (n = 32), 62% had Functional Independence Measure quotients of >0.75.

Conclusions: Mitochondrial diseases in children span a wide range of symptoms and severities. Age at first symptoms is the strongest predictor mortality. Despite a high mortality rate in the cohort, 62% of patients aged >5 years have only mild impairment or normal functional outcome.

MeSH terms

  • Cause of Death*
  • Child
  • Child, Preschool
  • Cohort Studies
  • DNA Fragmentation
  • DNA, Mitochondrial / genetics*
  • Female
  • Follow-Up Studies
  • Humans
  • Infant
  • Infant, Newborn
  • MELAS Syndrome / diagnosis
  • MELAS Syndrome / mortality
  • MELAS Syndrome / therapy
  • Male
  • Mitochondrial Diseases / diagnosis*
  • Mitochondrial Diseases / genetics
  • Mitochondrial Diseases / mortality*
  • Mitochondrial Encephalomyopathies / diagnosis
  • Mitochondrial Encephalomyopathies / mortality
  • Mitochondrial Encephalomyopathies / therapy
  • Mitochondrial Myopathies / diagnosis
  • Mitochondrial Myopathies / genetics
  • Mitochondrial Myopathies / mortality
  • Optic Atrophy, Hereditary, Leber / diagnosis
  • Optic Atrophy, Hereditary, Leber / genetics
  • Optic Atrophy, Hereditary, Leber / mortality
  • Probability
  • Proportional Hazards Models
  • Retrospective Studies
  • Severity of Illness Index
  • Survival Analysis
  • Time Factors


  • DNA, Mitochondrial