[Early mitochondrial encephalomyopathy due to complex IV deficiency consistent with Alpers-Huttenlocher syndrome: report of two cases]

Rev Neurol. 1999 Nov 16-30;29(10):912-7.
[Article in Spanish]


Introduction: Complex IV or cytochrome c oxidase (COX) deficiency is the most common disorder involving complexes of the respiratory chain in the pediatric age. Exceptionally, it has been reported in association with Alpers syndrome or Alpers disease, and with its variant named progressive neuronal degeneration with liver disease or Alpers-Huttenlocher syndrome.

Objective: To report the cases of two infants with mitochondrial encephalomyopathy due to COX deficiency in whom the clinical, biochemical, neurophysiologic and neuroimaging characterization suggested an associated Alpers-Huttenlocher syndrome.

Clinical cases: Two no-related males, one with noncontributory family history and the other with third-grade consanguineous parents developed refractory seizures from age 20 and 60 days, respectively. Additionally, myoclonic fits accounted on evolution of the condition. In the first case, serial EEG recordings showed low amplitude polyspikes, polyspike waves and very slow waves of high amplitude alternating with a trace of burst-suppression activity. In the second case, a right preponderant but also bilateral low amplitude polyspikes, polyspike waves and occasional desynchronization of basal trace were recorded. In both, a rapidly progressive cerebral atrophy, neurological deterioration with pyramidal signs, and tendency to microcephaly, ensued. Accompanying to this clinical picture, minor hepatic dysfunction, elevated protein levels in the CSF, lactic acidosis and COX deficiency in muscle homogenate were demonstrated. In the first case, moreover, cortical blindness and severe hepatic failure occurred while receiving valproate, in spite of concomitant L-carnitine therapy.

Conclusions: We believe that the reported cases are consisted with Alpers-Huttenlocher syndrome associated with mitochondrial encephalomyopathy due to COX deficiency. Nevertheless, early myoclonic encephalopathy, a condition related in same cases with poliodistrophy, must be keep in mind as a possible diagnosis in case 1.

Publication types

  • Case Reports
  • English Abstract

MeSH terms

  • Anticonvulsants / adverse effects
  • Atrophy / pathology
  • Cerebral Cortex / pathology
  • Cerebrospinal Fluid Proteins / analysis
  • Cytochrome-c Oxidase Deficiency*
  • Diagnosis, Differential
  • Diffuse Cerebral Sclerosis of Schilder / diagnosis*
  • Disease Progression
  • Electroencephalography
  • Humans
  • Infant
  • Leigh Disease / complications*
  • Leigh Disease / diagnosis*
  • Liver Failure / chemically induced
  • Magnetic Resonance Imaging
  • Male
  • Mitochondrial Encephalomyopathies / etiology*
  • Seizures / complications
  • Seizures / drug therapy
  • Valproic Acid / adverse effects


  • Anticonvulsants
  • Cerebrospinal Fluid Proteins
  • Valproic Acid