Bezafibrate can be a new treatment option for mitochondrial fatty acid oxidation disorders: evaluation by in vitro probe acylcarnitine assay.

BACKGROUND: The number of patients with mitochondrial fatty acid oxidation (FAO) disorders is recently becoming larger with the spread of newborn mass screening. Despite the advances in metabolic and molecular characterization of FAO disorders, the therapeutic studies are still limited. It was reported recently that bezafibrate (BEZ), an agonist of peroxisome proliferating activator receptor (PPAR), can restore FAO activity in cells from carnitine palmitoyltransferase-2 (CPT2) and very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiencies as well as clinical symptoms in the adult patients. METHODS: In this study, the therapeutic effect of BEZ was determined by in vitro probe acylcarnitine (IVP) assay using cultured fibroblasts and tandem mass spectrometry on various FAO disorders. The clinical trial of BEZ treatment for a boy with the intermediate form of glutaric acidemia type 2 (GA2) was also performed. RESULTS: The effect of BEZ was proven in cells from various FAO disorders including GA2, deficiencies of VLCAD, medium-chain acyl-CoA dehydrogenase, CPT2, carnitine acylcarnitine translocase and trifunctional protein, by the IVP assay. The aberrantly elevated long- or medium-chain acylcarnitines that are characteristic for each FAO disorder were clearly corrected by the presence of BEZ (0.4 mmol/L) in culture medium. Moreover, daily administration of BEZ in a 2-year-old boy with GA2 dramatically improved his motor and cognitive skills, accompanied by sustained reduction of C4, C8, C10 and C12 acylcarnitines in blood, and normalized the urinary organic acid profile. No major adverse effects have been observed. CONCLUSION: These results indicate that BEZ could be a new treatment option for FAO disorders.

A pediatric case of food-dependent exercise-induced anaphylaxis due to rice bran.

Food-dependent exercise-induced anaphylaxis (FDEIA) caused by fruits and vegetables is increasing in recent years, but rice-induced FDEIA is rarely reported. The mechanism of FDEIA is unclear, although percutaneous sensitization occurs in some cases. A 14-year-old adolescent came our hospital who had 6 episodes of unknown FDEIA occurring from age 13. He affected atopic dermatitis in infancy, and he had been polishing rice daily to help with housework, and also had occasionally begun to observe urticaria while bathing after eating rice from 5 years old. Antigen-specific immunoglobulin E antibody titers (ImmunoCAP) were 1.35 UAmL for rice, 23.6 UAmL for orchard grass. Oral food challenge and exercise provocation test with polished rice were negative. An oral food challenge with rice bran was also negative, but exercise provocation test induced severe anaphylaxis. IgE immunoblotting with rice bran detected patient-specific bands, as 25-, 35-, 50-, and 60 kDa, and the 25- and 60-kDa bands were heat-resistant. In a suppression test using rice bran, these bands disappeared or diminished. In an inhibition test against orchard grass pollen with rice bran, inhibition was not observed. Conversely, an inhibition test against rice bran with orchard grass pollen, inhibition was observed in a concentration-dependent manner. This is extremely rare case of FDEIA in children, caused by rice bran. Furthermore, it might be induced by percutaneous sensitization. In FDEIA, it is necessary to scrutinize the possibility that rice bran may be the cause even in children.