Early-onset cerebellar ataxia, myoclonus and hypogonadism in a case of mitochondrial complex III deficiency treated with vitamins K3 and C

J Neurol. 1995 Mar;242(4):203-9. doi: 10.1007/BF00919592.

Abstract

A 16-year-old girl presented with early-onset cerebellar ataxia, myoclonus, elevated lactic acidosis and hypogonadotropic hypogonadism. Muscle biopsy specimens revealed fibres with a "ragged" appearance with increased mitochondria and lipid droplets. Biochemical investigation revealed a deficiency of complex bc1 (complex III) of the mitochondrial respiratory chain. Genetic analysis did not show either deletions or known mutations of mitochondrial DNA (mtDNA). Phosphorus magnetic resonance spectroscopy (31P-MRS) showed defective energy metabolism in brain and gastrocnemius muscle. A decreased phosphocreatine (PCr) content was found in the occipital lobes accompanied by normal inorganic phosphate (Pi) and cytosolic pH. These findings represented evidence of a high cytosolic adenosine diphosphate concentration and a relatively high rate of metabolism accompanied by a low phosphorylation potential. Muscle 31P-MRS showed a high Pi content at rest, abnormal exercise transfer pattern and a low rate of PCr post-exercise recovery. These findings suggested a deficit of mitochondrial function. Therapy with vitamins K3 and C normalized brain 31P-MRS indices, whereas it did not affect muscle bioenergetic metabolism. In this patient, the endocrinological disorder is putatively due to a mitochondrial cytopathy. Although an unknown mtDNA mutation cannot be ruled out, the genetic defect may lie in the nuclear genome.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age of Onset
  • Ascorbic Acid / therapeutic use*
  • Consanguinity
  • DNA, Mitochondrial / genetics
  • Electron Transport / drug effects
  • Electron Transport Complex III / deficiency*
  • Female
  • Humans
  • Magnetic Resonance Spectroscopy
  • Mitochondria / drug effects
  • Mitochondria / enzymology*
  • Mitochondria / genetics
  • Myoclonic Cerebellar Dyssynergia / etiology*
  • Vitamin K / therapeutic use*

Substances

  • DNA, Mitochondrial
  • Vitamin K
  • Electron Transport Complex III
  • Ascorbic Acid