Phenotype variability in 130 adult patients with respiratory chain disorders

J Inherit Metab Dis. 2001 Oct;24(5):560-76. doi: 10.1023/a:1012415810881.


Despite continuously improving diagnostic facilities, respiratory chain disorders (RCDs) are easily overlooked or misdiagnosed. We thus studied phenotype variability and the diagnostic potential of clinical and laboratory investigations in patients with RCD. We retrospectively evaluated clinical and laboratory investigations in 130 patients with RCD: 63 women and 67 men, aged 17-87 years, diagnosed between January 1992 and December 1999. mtDNA mutations were found in 20 patients; a respiratory chain defect but no mutation in 4; an abnormal lactate stress test but no mutation or biochemical defect in 66; and ragged-red fibres or reduced oxidative enzyme staining but no mutation, biochemical defect or abnormal lactate stress test in 40 patients. The most frequent initial manifestation of RCD were limb weakness, muscle pain and sensory disturbances. The most frequent clinical findings at diagnosis were muscle pain, fatiguability, limb weakness, reduced tendon reflexes and muscle wasting, irrespective of the diagnostic evidence. Mean age at onset, disease duration and time until diagnosis were 39, 14 and 13 years, respectively, without sex differences. The family history was positive in 29% of the patients. Hyperlipidaemia was found in 45%, hyper-CK-aemia in 42%, short stature in 33%, thyroid dysfunction in 17%, diabetes in 12%, and epilepsy in 8% of the patients. Laboratory investigations that prove useful to support the diagnosis of RCD are muscle biopsy, electromyography, lactate stress testing, echocardiography and mtDNA analysis. Systems most often involved in RCDs were the PNS, CNS, endocrine system and heart. The diagnosis of RCD requires awareness of the great phenotypic heterogeneity and an individualized, integral, multidisciplinary approach.

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Aged
  • Aged, 80 and over
  • Aging / metabolism
  • Body Height / physiology
  • DNA, Mitochondrial / analysis
  • DNA, Mitochondrial / genetics
  • DNA, Mitochondrial / metabolism
  • Disease Progression
  • Electron Transport / genetics
  • Electron Transport / physiology*
  • Enzymes / blood
  • Female
  • Gene Frequency
  • Humans
  • Male
  • Metabolism, Inborn Errors / diagnosis
  • Metabolism, Inborn Errors / genetics*
  • Metabolism, Inborn Errors / pathology
  • Middle Aged
  • Mitochondria / genetics*
  • Mitochondria / metabolism
  • Mitochondria / pathology
  • Muscle, Skeletal / pathology
  • Phenotype
  • Retrospective Studies
  • Sex Characteristics


  • DNA, Mitochondrial
  • Enzymes