Journal of Inherited Metabolic Disease

, Volume 33, Issue 5, pp 527–532 | Cite as

Mitochondrial fatty acid oxidation disorders: clinical presentation of long-chain fatty acid oxidation defects before and after newborn screening

  • Ute SpiekerkoetterEmail author
Fatty Acid Oxidation


The different long-chain fatty acid oxidation defects present with similar heterogeneous clinical phenotypes of different severity. Organs mainly affected comprise the heart, liver, and skeletal muscles. All symptoms are reversible with sufficient energy supply. In some long-chain fatty acid oxidation defects, disease-specific symptoms occur. Only in disorders of the mitochondrial trifunctional protein (TFP) complex, including long-chain 3-hydroxyacyl-coenzyme A (CoA) dehydrogenase (LCHAD) deficiency, neuropathy and retinopathy develop that are progressive and irreversible despite current treatment measures. In most long-chain fatty acid oxidation defects, no clear genotype–phenotype correlation exists due to molecular heterogeneity. However, some isolated mutations have been identified to be associated with only mild phenotypes, e.g., the V243A mutation in very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency. LCHAD deficiency is due to the prevalent homozygous 1528G>C mutation and presents with heterogeneous clinical phenotypes, suggesting the importance of other environmental and genetic factors. For some disorders, it was shown that residual enzyme activity measured in fibroblasts or lymphocytes correlated with severity of clinical phenotype. Implementation of newborn screening has significantly reduced morbidity and mortality of long-chain fatty acid oxidation defects. However, the severest forms of TFP deficiency are still highly associated with neonatal death. Newborn screening also identifies a great number of mildly affected patients who may never develop clinical symptoms throughout life. However, later-onset exercise-induced myopathic symptoms remain characteristic clinical features of long-chain fatty acid oxidation defects. Disease prevalence has increased with newborn screening.


Newborn Screening HELLP Syndrome Fatty Acid Oxidation Disorder Electron Transfer Flavoprotein Fatty Acid Oxidation Defect 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Acyl-CoA dehydrogenase 9


Carnitine acylcarnitine translocase


Carnitine palmitoyl-CoA transferase 1


Carnitine palmitoyl-CoA transferase 2


Glutaric aciduria type II (= electron transfer defect = MAD deficiency)


Long-chain acyl-CoA dehydrogenase


Long-chain 3-hydroxyacyl-CoA dehydrogenase


Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency


Long-chain 3-ketoacyl-CoA thiolase


Multiple acyl-CoA dehydrogenase


Medium-chain acyl-CoA dehydrogenase


Mitochondrial trifunctional protein


Organic cation carnitine transporter 2


Very-long-chain acyl-CoA dehydrogenase


Very-long-chain acyl-CoA dehydrogenase deficiency


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Copyright information

© SSIEM and Springer 2010

Authors and Affiliations

  1. 1.Department of General PediatricsUniversity Children’s HospitalDuesseldorfGermany

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