Glucose metabolism and diet-based prevention of liver dysfunction in MPV17 mutant patients

J Hepatol. 2009 Jan;50(1):215-21. doi: 10.1016/j.jhep.2008.08.019. Epub 2008 Oct 31.

Abstract

Background/aims: To describe in detail the specific clinical and biological characteristics of three patients with MPV17 gene mutations, a rare hepatocerebral mitochondrial DNA depletion syndrome (MDS) and the positive effects of a novel dietetic treatment based on avoidance of fasting.

Methods: We describe the case histories of three members of the same family with MPV17 mutations.

Results: Two patients had a very severe and progressive liver disease: 1 died in the first year of life and the other underwent liver transplantation. The third patient, now 13 years of age, had a milder form of liver disease and developed progressive ataxia. Psychomotor involvement at onset of disease was mild or absent. No patient had severe hyperlactataemia. In vivo functional studies on two patients showed no hyperlactataemia even after intravenous and oral glucose loading, regular fasting hypoglycemia 3-4h after meals and no response to glucagon. Liver function tests improved when patients received continuous iv glucose infusion or were regularly fed every 3h.

Conclusions: These clinical and biochemical features allow us to differentiate patients with MPV17 mutations from other liver MDS and suggest that regular glucose intake at short intervals may be beneficial in slowing the progression of the disease.

Publication types

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

MeSH terms

  • Adolescent
  • Alanine Transaminase / blood
  • Aspartate Aminotransferases / blood
  • Biopsy
  • Child, Preschool
  • Disease Progression
  • Female
  • Glucose / metabolism*
  • Glucose / therapeutic use*
  • Humans
  • Infant
  • Liver / pathology
  • Liver Diseases / diet therapy*
  • Liver Diseases / genetics
  • Liver Diseases / prevention & control*
  • Male
  • Membrane Proteins / genetics*
  • Mitochondrial Diseases / genetics*
  • Mitochondrial Proteins / genetics*
  • Mutation / genetics*
  • Pedigree

Substances

  • MPV17 protein, human
  • Membrane Proteins
  • Mitochondrial Proteins
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Glucose