The clinical characteristics and genetic mutations of 2 patients with mitochondrial trifunctional protein (TFP) deficiency were published in the journal Molecular Medicine Reports.
TFP deficiency is 1 of 6 types of long chain fatty acid oxidation disorders (LCFAODs) and can be caused by mutations in the HADHA or HADHB genes.
The cases presented here have mutations in the HADHA gene, which is a first in the Chinese population. Only 2 other cases of TFP deficiency cases have been reported in this population, but these were caused by a mutation in the HADHB gene.
“The present study may improve understanding of the HADHA gene mutation spectrum and clinical phenotype in the Chinese population,” the authors of the study wrote.
They reported that both patients had abnormal levels of lactate dehydrogenase, creatine kinase, and liver enzymes. Their blood levels of long‑chain acyl‑carnitine were markedly elevated. They both experienced metabolic crises caused by low blood sugar and the build-up of toxic substances in the blood and died due to infectious diseases.
Read more about LCFAOD causes
The autopsy results of 1 of the patients showed that long‑chain acyl‑carnitine accumulated in the liver and heart. Exome sequencing revealed that he had the compound heterozygous mutations in the HADHA gene c.703C>T (p.R235W) and c.2107G>A (p.G703R), 1 inherited from each parent.
Genetic testing of the other patient also showed the same compound heterozygous mutations in the HADHA gene. These 2 patients had an older sister who had the c.703C>T (p.R235W) mutation and the mother was pregnant with a fourth child who had the c.2107G>A (p.G703R) mutation.
Both parents and the first sister were asymptomatic and had normal levels of long‑chain acyl‑carnitine. “The clinical phenotypes of the two heterozygous variants of the HADHA gene are non-lethal,” the researchers concluded.
They also conducted mechanistic analyses of the protein and showed that the 2 variants affected the conformation of the α‑subunit and therefore the stability and function of the TFP complex.
Yang J, Yuan D, Tan X, et al. Analysis of a family with mitochondrial trifunctional protein deficiency caused by HADHA gene mutations. Mol Med Rep. 2022;25(2):47. doi:10.3892/mmr.2021.12563