The clinical and molecular characteristics of 4 patients with trifunctional protein (TFP) deficiency and 1 with long-chain 3-hydroxy-acyl-CoA dehydrogenase (LCHAD) deficiency, 2 types of long chain fatty acid oxidation disorder (LCFAOD) were described in the first of this year’s lecture series of the International Network for Fatty Acid Oxidation Research and Management (INFORM). The aim was to identify a possible correlation between genotype and molecular phenotype.

Only the patient with LCHAD deficiency was homozygous, while 2 patients who had a mutation in the HADHA gene were compound heterozygous. Two of the patients who had a mutation in the HADHA gene had cardiomyopathy, while 1 who had a mutation in the HADHB gene also had cardiomyopathy while the other did not. 

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During his presentation, Eduardo Vieira Neto, MD, PhD, from the Division of Genetic and Genomic Medicine, Department of Pediatrics, School of Medicine, University of Pittsburgh, UPMC Children’s Hospital of Pittsburgh, described the structure of the patients’ TFP, the expression of their mRNA, mitochondrial bioenergetics and phospholipids, and acylcarnitine profiles.  

Dr. Neto first showed that glutamate was essential for the catalytic activity of LCHAD. He also reported that protein expression was preserved in the patients with LCHAD deficiency as well as another patient who had cardiomyopathy and variability in mRNA decay among patients. 

Then Dr. Neto moved on to the effect of the mutations on mitochondrial respiration and ATP production. He showed that with some mutations, the mitochondrial bioenergetics was maintained. However, a clear reduction in maximal respiration and spare respiratory capacity was seen in all TFP/LCHAD fibroblasts grown in culture compared to controls, he reported. 

In terms of mitochondrial phospholipids, Dr. Neto reported that levels of cardiolipin decreased while that of monolyso-cardiolipin increased in TFP/LCHAD deficiency compared to controls but with some variability between the different patients.

Finally, Dr. Neto reported on the levels of acylcarnitine and said that there were also some variations between patients. 


Neto EV. Correlation of genotype and molecular phenotype in mitochondrial trifunctional protein deficiency. Lecture presented at the International Network for Fatty Acid Oxidation Research and Management (INFORM) 2023 lecture series: January 23, 2023; Virtual.