Trifunctional protein deficiency

Matern D, Strauss AW, Hillman SL, Mayatepek E, Millington DS, Trefz FK (1999) Diagnosis of mitochondrial trifunctional protein deficiency in a blood spot from the newborn screening card by tandem mass spectrometry and DNA analysis. Pediatr Res 46 45-49... 

Hintz SR, Matern D, Strauss A, et al (2002) Early neonatal diagnosis of long-chain 3-hydroxy-acyl coenzyme a dehydrogenase and mitochondrial trifunctional protein deficiencies. Mol Genet Metab 75 120-127... 

Kamijo, T., Wanders, J.A., Saudubray, J.-M., Aoyama, T., Komiyama, A. Hashimoto, T. (1994) J. Clin. Invest. 93, 1740-1747. Mitochondrial trifunctional protein deficiency. Catalytic heterogeneity of the mutant enzyme in two patients. 

A second, cytosolic CPS activity (CPSII) occurs in mammals as part of the CAD trifunctional protein that catalyzes the first three steps of pyrimidine synthesis (CPSII, asparate tran-scarbamoylase, and dihydroorotase). The activities of these three enzymes—CPSII, aspartate transcarbamoylase, and dihydroorotase—result in the production of orotic acid from ammonium, bicarbonate, and ATP. CPSII has no role in ureagenesis, but orotic aciduria results from hepatocellular accumulation of carbamyl phosphate and helps distinguish CPSI deficiency from other UCDs. Defects in CPSI classically present with neonatal acute hyperammonemic encephalopathy. The plasma citrulline and urine orotic acid concentrations are both low. A definitive diagnosis can be established by enzyme assay of biopsied liver tissue or by mutation analysis. 

Trifunctional Protein and Long-Chain 3-Hydroxy Acyl-CoA Dehydrogenase Deficiencies... 

Ijlst L, Ruiter JP, Hoovers JM, Jakobs ME, Wanders RJ. Common missense mutation G1528C in long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency. Characterization and expression of the mutant protein, mutation analysis on genomic DNA and chromosomal localization of the mitochondrial trifunctional protein alpha subunit gene. J Clin Invest 1996 98 1028-33. 

Ijlst, L., Wanders, R.J.A., Ushikubo, S, Kamijo, T. Hashimoto, T. (1994) Biochim. Biophys. Acta 1215, 347-350. Molecular basis of long chain 3-hydroxyacyl-CoA dehydrogenase deficiency identification of the major disease-mutation in the a-subunit of the mitoehondrial trifunctional protein. 

Gillingham MB, et al. Metabolic control during exercise with and without medium-chain triglycerides (MCT) in children with long-chain 3-hydroxy acyl-CoA dehydrogenase (LCHAD) or trifunctional protein (TFP) deficiency. Mol Genet Metab. 2006 89(l-2) 58-63. 

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