The inborn errors of mitochondrial fatty acid oxidation

J Inherit Metab Dis. 1987:10 Suppl 1:159-200. doi: 10.1007/BF01812855.

Abstract

To date, seven inborn errors of mitochondrial fatty acid oxidation have been identified. A total of about 100 patients in the world have been reported. Clinically the beta-oxidation defects are more often characterized by episodic hypoglycaemia leading to a coma mimicking Reye's syndrome. The hypoglycaemia is non-ketotic since the synthesis of ketone bodies is deficient. Periods of decompensation occur when carbohydrate supply is poor, e.g. prolonged fasting, vomiting, or increased caloric requirements, as and when lipid stores are used. Defects in beta-oxidation have also been reported to be one cause of sudden infant death syndrome. The diagnosis of these inborn errors is by biochemical investigation since where symptoms suggest such a defect, the precise aetiology cannot be assessed. The biochemical diagnosis is based firstly on identification of abnormal plasma and of urinary metabolites during acute attacks. Derivatives of the omega-oxidation and omega-1-oxidation of medium chain fatty acids have been identified, as well as acylglycine and acylcarnitine conjugates. These metabolites are nearly always absent when patients are in good clinical condition. Secondly, the diagnosis must be based on the identification of the enzymatic defects: this involves global assays which allow a localization of the 'level' of the defect (i.e. the oxidation of long, medium or short chain fatty acids) and specific measurement of enzyme activities (acyl-CoA dehydrogenases and electron carriers: ETF and ETF-DH). The diagnosis of these disorders is of prime importance because of the severity of the clinical symptoms. These can be prevented, in some cases, by an appropriate diet (a high carbohydrate, low fat diet, sometimes supplemented with L-carnitine). In other cases, genetic counselling can be offered.

Publication types

  • Review

MeSH terms

  • Carnitine / deficiency
  • Diagnosis, Differential
  • Electron-Transferring Flavoproteins
  • Fatty Acid Desaturases / deficiency
  • Fatty Acids / metabolism*
  • Flavoproteins / deficiency
  • Glutarates / urine
  • Humans
  • Iron-Sulfur Proteins*
  • Lipid Metabolism, Inborn Errors / diagnosis
  • Lipid Metabolism, Inborn Errors / drug therapy
  • Lipid Metabolism, Inborn Errors / metabolism*
  • Microbodies / metabolism
  • Mitochondria / metabolism*
  • Multienzyme Complexes / deficiency
  • Oxidation-Reduction
  • Oxidoreductases Acting on CH-NH Group Donors*
  • Riboflavin / therapeutic use

Substances

  • Electron-Transferring Flavoproteins
  • Fatty Acids
  • Flavoproteins
  • Glutarates
  • Iron-Sulfur Proteins
  • Multienzyme Complexes
  • Fatty Acid Desaturases
  • Oxidoreductases Acting on CH-NH Group Donors
  • electron-transferring-flavoprotein dehydrogenase
  • glutaric acid
  • Carnitine
  • Riboflavin