The early-onset phenotype of mitochondrial trifunctional protein deficiency: a lethal disorder with multiple tissue involvement.

Mitochondrial trifunctional protein (TFP) deficiency is a clinically heterogeneous disorder with phenotypes of different severity. Early onset, severe forms predominantly exhibit cardiomyopathy, life-threatening arrhythmias and liver dysfunction; the later-onset, milder phenotype is mainly characterized by neuromyopathic features. The mechanisms that determine these heterogeneous presentations are unknown. We performed multiple tissue immunoblots from a patient with early-onset, lethal TFP deficiency and demonstrated absent TFP antigen in all. The predominant cardiac manifestation of severe TFP deficiency reflects its essential role in myocardial energetics, not its tissue-specific expression.