Periodic Paralysis in a Child With Thermosensitive Mitochondrial Trifunctional Protein Deficiency.

Mitochondrial trifunctional protein (MTP) deficiency is a fatty acid oxidation disorder associated with a spectrum of phenotypes. Patients with high residual enzyme activity tend to have milder phenotypes, and recently, fever-induced episodic myopathy was reported in association with a thermosensitive form of MTP deficiency. We report a 10-year-old male with recurrent episodes of acute flaccid paralysis involving upper and lower extremities in association with bulbar muscle weakness in the context of febrile illness, a phenotype reminiscent of recurrent periodic paralysis.

Disorders of fatty acid homeostasis.

Humans derive fatty acids (FA) from exogenous dietary sources and/or endogenous synthesis from acetyl-CoA, although some FA are solely derived from exogenous sources ("essential FA"). Once inside cells, FA may undergo a wide variety of different modifications, which include their activation to their corresponding CoA ester, the introduction of double bonds, the 2- and ω-hydroxylation and chain elongation, thereby generating a cellular FA pool which can be used for the synthesis of more complex lipids. The biological properties of complex lipids are very much determined by their molecular composition in terms of the FA incorporated into these lipid species.

Tracer-based lipidomics enables the discovery of disease-specific candidate biomarkers in mitochondrial β-oxidation disorders.

Carnitine derivatives of disease-specific acyl-CoAs are the diagnostic hallmark for long-chain fatty acid β-oxidation disorders (lcFAOD), including carnitine shuttle deficiencies, very-long-chain acyl-CoA dehydrogenase deficiency (VLCADD), long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) and mitochondrial trifunctional protein deficiency (MPTD). The exact consequence of accumulating lcFAO-intermediates and their influence on cellular lipid homeostasis is, however, still unknown. To investigate the fate and cellular effects of the accumulating lcFAO-intermediates and to explore the presence of disease-specific markers, we used tracer-based lipidomics with deuterium-labeled oleic acid (D9-C18:1) in lcFAOD patient-derived fibroblasts.