Medium-chain acyl-CoA dehydrogenase MCAD deficiency

Medium chain acyl CoA dehydrogenase (MCAD) deficiency, primary etiology hepatic... 

Van Hove JL, Zhang W, Kahler SG, Roe CR, Chen YT, Terada N, et al. Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency diagnosis by acylcarnitine analysis in blood. Am J Hum Genet 1993 52 958-66. 

Recently, medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, j the cause of Lofata Bume s problems, has emerged as one of the most — common of the inborn errors of metabolism, with a carrier frequency ranging from 1 in 40 in northern European populations to less than 1 in 100 in Asians. Overall, the predicted disease frequency for MCAD deficiency is 1 in 15,000 persons. 

Andresen, B.S, Bioss P. Udvari, S. et al. (1997)HimumMolecular Genetics6, 695-707 The molecular basis of medium-chain acyl-CoA-dehydrogenase (MCAD) deficiency in compound heterozygous patients is there correlation between genotype and phenotype ... 

Gregersen N., Andiesen B.S., Bross P., Bolund L. Kolvraa S. (1994) Disorders of mitochondrial fatty acid oxidation especially medium-chain acyl-CoA dehydrogenase (MCAD) deficiency. In Farriaux J.P. Dhondt J.L. eds New Horizons in Neonatal Screening. Elsevier Science BV, pp 247-55. 

Bross P., Jespersen C, Jensen T.G., Andresen B.S, Kristensen M.J., Winter A, Nandy A., Krautle F., Ghisla S., Bolund L., Kim J.-J.P. Gregersen N. (1995) Effects of two mutations detected in medium-chain acyl-CoA dehydrogenase (MCAD)-deficient patients on folding, oligomer assembly and stability of MCAD enzyme. J Biol Chem 270 10284-90. 

Missense mutations and small insertion/dele-tion mutations frequently result in protein mis-folding. In fact, this is a common finding in PKU [8-10], medium-chain acyl-CoA dehydrogenase (MCAD deficiency) [11], and galactosemia [12, 13], Nonsense mutations commonly lead to a short, truncated protein, or loss of protein expression. The frequency of the type of mutation varies with disease. In PKU the two most common types of mutations are missense mutations (60.1 %) and deletions (13.4 %) [14]. 

Carnitine and its esters (see [1]) cannot be introduced to the mass spectrometer by gas chromatography, as they incorporate quaternary amine functions and will decompose in the attempt. Fast atom bombardment (FAB) and electrospray ionization (ESI) can use the formal charge on the quaternary amine function to advantage, as carnitine and its esters are very easily desorbed from glycerol on the FAB probe and from aerosol sprays in ESI. Eigure 7A illustrates the use of EAB in the quantitation of carnitine and its esters excreted in the urine of a patient presenting with a severe dicarboxylic aciduria associated with medium-chain acyl-CoA dehydrogenase (MCAD) deficiency. 

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