MCAD medium-chain fatty deficiency

Medium-chain fatty acyi CoA dehydrogenase (MCAD) deficiency impairs metaboiism of medium-chain (C6-Ci2) fatty acids. 

A couple has a child who has been diagnosed with medium-chain acyl coenzyme A (CoA) dehydrogenase deficiency (MCAD), a condition that allects the body s ability to metabolize medium-chain fatty acids. This couple is now expecting another child. What is the risk that this child will have MCAD ... 

Medium-chain fatty acid (6-12 carbons) oxidation disorders Medium-chain acyl-CoA dehydrogenase deficiency (MCAD)... 

Among the fatty acid oxidation disorders, medium-chain acyl-CoA dehydrogenase deficiency (MCAD) is the most common and its frequency is similar to that of phenylketonuria. The disorder can be identified by mutant alleles and some key abnormal metabolites. An A G transition mutation occurs at position 985 of MCAD-cDNA in about 90% of cases. This mutation leads to replacement of lysine with glutamate at position 329 (K329E) of the polypeptide. 

As noted above, there have been reports that link some cases of APLP with a defect in fatty acid metabolism in the fetus. These include fetal deficiencies of long chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD), carnitine-palmitoyl transferase 1 (CPT 1), and medium chain acyl-coenzyme A dehydrogenase (MCAD). The mechanism by which defective fetal fatty acid oxidation causes maternal illness is not known. However, since the fetus uses primarily glucose metabolism for its energy needs, it is likely that toxic products from the placenta, which does use fatty acid oxidation, cause the maternal liver failure. 

Compared with controls, 22 6n-3 biosynthesis was normal in cells from patients with deficiencies of the mitochondrial fatty acid p-oxidation enzymes, vay-long-chain acyl-CoA dehydrogenase (VLCAD) or medium-chain acyl-Co A dehydrogenase (MCAD) (Table 2). These findings confirmed that retro-conversion of 24 6n-3 to 22 6n-3 is via the peroxisomal, but not mitochondrial fatty acid p-oxidation pathway. 

Sometimes a test for more than one protein is needed and mass spectrometry is the method of choice for that purpose. A good example for this would be the use of tandem mass spectrometry to screen neonates for metabolic disorders such as amino acidemias (e.g., phenylketonuria—PKU), organic acidemias (e.g., propionic acidemia—PPA), and fatty acid oxidation disorders (e.g.. Medium-chain acyl-CoA Dehydrogenase deficiency—MCAD) [9]. Although the price of this capital equipment could be high, costs of using it as a sensor is quite low (usually < U.S. 50.00 to screen for more than 20 metabolic disorders), and many states in the United States provide the service to newborns during the first week of life. 

Comparison of the absolute and relative activities obtained with fliese two substrates can often pinpoint the nature of the fatty acid oxidation defect. Medium chain acyl-CoA dehydrogenase deficiency (MCAD) is characterised by a much decreased oxidation of myristate and a high palmitate/myristate (P/M) ratio, mean percentage activity relative to simultaneous controls being 11.5 5.1 (n = 18) with a corresponding P/M ratio of 4.6 1.7 (Fig. 1). 

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., Jensen T.G., Krautle E, Winter V., Andresen B.S., Engst S., Bolund L., Kolvraa S, Ghisla S, Rasched 1. Gregersen N. (1992) Characterisation of medium-chain acyl-Co A dehydrogenase (MCAD) with a point mutation associated with MCAD deficiency. In New Developments in Fatty Acid Oxidation, Coates P.M. Tanaka K. eds, pp 473-8. Wiley-Liss, New York. 

MCAD deficiency. The most frequent inborn error of fatty acid oxidation (1 12000 to 20000 in Caucasians from northern Europe). It affects the medium chain acyl-CoA dehydrogenase and in around 80% of the affected alleles a single common missense mutation has been identified. Symptoms typically appear during infancy or early childhood and can include vomiting, lethargy and hypoglycaemia. 

When the suspicion of a long-chain fatty acid oxidation defect is substantial, additional proof can be found by a medium-chain triglyceride (MCT) loading test. This should result in normal ketogenesis, except in patients with MCAD and HMGS deficiency. The value of the latter test is limited. 

Fatty acid oxidation defects cover a wide range of enzyme deficiencies in the metabolism of long-, medium-, and short-chain fats. Patients with LCFAOD and MCAD can present with severe illness or be asymptomatic. Chronic management of LCFAOD involves the restriction of long-chain fat and supplementation of MCT, a readily used source of energy that is not dependent on enzymes used in long-chain... 

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