Mitochondrial trifunctional protein (MTP) deficiency presenting with late-onset cardiomyopathy phenotype

Case presentation: Female, 4 years old, hospitalized for coughing and reduced level of consciousness. Physical examination revealed tachycardia, no response to stimuli, isochoric and photoreactive pupils. Diagnostic hypotheses of viral encephalitis and myocarditis were raised after laboratory tests did not suggest sepsis. During admission to the Intensive Care Unit, skull computed tomography and cerebrospinal fluid were normal. Anti-cytomegalovirus serum dosage IgM positive. Evolved with hemodynamic decompensation and prolonged cardiorespiratory arrest, creatine phosphokinase of 23.971, creatine kinase-MB fraction of 950, elevation of transaminases, troponin levels of 703. Post-arrest cranial resonance showed images suggestive of bilateral hypoxic-ischemic white matter lesions. Due to the brother's history of early death at 18 months due to sepsis, we chose to perform tandem mass spectrometry and plasma acylcarnitine profile, which indicated a probable diagnosis of Very Long-Chain Acyl-CoA Dehydrogenase deficiency (VLCADD) with subsequent confirmation of Mitochondrial Trifunctional Protein (MTP) deficiency through specific molecular genetic test. Treatment with triheptanoin was initiated and a gradual improvement in the level of consciousness, cognitive functions, cardiac parameters and reduction of muscle and liver enzymes were observed.

Discussion: MTP deficiency is a rare autosomal recessive disorder affecting long-chain fatty acid oxidation caused by mutations in the HADHB gene and is associated with 3 main clinical phenotypes: early-onset of a severe and lethal cardiomyopathic disease, infantile-onset of a hepatic dysfunction and recurrent hypoketotic hypoglycemia and late-onset of skeletal myopathy and peripheral neuropathy. Reports and clinical trials of anaplerotic therapy with triheptanoin have demonstrated an improvement in cardiac symptoms, muscle weakness, hypoglycemia, and hepatomegaly with good security profile and reduced hospitalizations.

Final comments: In view of the clinical history of non-specific presentation, severe and acute evolution, premature death of a sibling, our objective is to present a challenging diagnosis with an unusual onset, which must be recognized on hospital admission of children with supposedly infectious disease, to modify the course of the disease with the treatments already available and reduce morbidity and mortality.

No conflict of interest has been declared by the author(s).

Publication History

Article published online:
18 September 2023