Nial Luu
University of New Hampshire - Durham


Medium chain acyl-coenzyme A dehydrogenase deficiency (MCADD) is a metatabolic disorder caused by genetic mutations. The purpose of this research is to investigate the evolutionary correlations between species against homo sapiens using BLAST search engine and MEGA sequence aligner to produce phylogenetic trees.


The enzyme, medium chain acyl-coenzyme A dehydrogenase (MCAD) is responsible for the dehydrogenation of fatty acids that undergo beta-oxidation in the mitochondria. MCAD specifically breaks down fatty acids of 6 to 12 carbon length into acetyl-CoA; which the acetyl group is delivered and processed through the citric acid cycle (Krebs cycle) to be oxidized for energy production.

Medium chain acyl-coenzyme A dehydrogenase deficiency (MCADD) is a disorder of the MCAD enzyme which impairs the body’s ability to perform fatty acmitochondrial beta-oxidation.pngid oxidation, specifically medium chain-triglycerides (MCT). This disorder leaves the body unable to utilize the medium-chain triglycerides during a period of fasting – a period of concentration elevation and essentially for energy production and maintenance of homeostasis. This results in hypoglycemia in patients presenting symptoms of dizziness, extreme hunger, inability to concentrate, confusion, blurred vision, pale skin, sweating, shaking, rapid heart rate, seizures, and eventually fatality without some dietary intervention and screening. Other symptoms experienced by individuals with MCADD include: hyperammonemia, gastritis, lethargy, seizure, coma, and sudden infant death syndrome-like illness. Sudden death will occur 20% of the time in individuals with MCADD (Dietrich M., 2015).

MCADD is an inherited recessive autosomal disorder of a mutated allele that involves the acyl-Coenzyme A dehydrogenase (ACADM) gene. This gene provides the code to formulating the acyl-coenzyme A dehydrogenase enzyme. The most frequent pathogenic variant of this disorder is a single base mutation, 985A>G (K304E mutant), and accounts for 90% of MCADD cases. This variant is especially prevalent in individuals of northern European descent. The K304E mutant has a similar prevalence observed in gypsies population of Portugal and Native Americans of California but this variant has not been detected in Asian descent populations. The most common variant in Asians is a mutation at 843A>T known as the R281S mutant (Oerton., et al 2005).

MCAD beta-oxidation spiral.jpgDiagnosis of MCAD deficiency demands a cumulative interpretation of multiple analysis testing tools to be able to formulate a precise and accurate diagnosis of MCADD. Initial testing includes a spectrum of biochemical tests that may include blood plasma acylcarnitine analysis, urine organic acid and arylglycine analysis, and determining the status of fatty acid β-oxidation by measuring the MCAD enzyme activity in leukocytes, fibroblasts, mitochondria, and other tissues. MCAD deficiency inhibits hepatic ketogenesis by impairing medium-chain fatty acid β-oxidation. Therefore if screened, carriers of MCADD will exhibit elevated levels of medium-chain acylcarnitines such as hexanoylcarintine (C6), octanoylcarnitine (C8), and decanoylcarintine (C10)(Dietrich M., 2015). If levels of these medium-chain fatty acids are elevated above normal average levels and hypoglycemia symptoms are present. This would be sufficient biochemical evidence for confirmation and the next step would be genetic testing.

Autosomal Recessive Inheritence Chart.gif
Based on newborn screening programs and studies, the prevalence of MCAD deficiency in North America is 1:23,400 live births. Europe 1:24,900 live births, England 1:10,700 live births, Denmark 1:900 live births, Greece 1:16,00, Italy 1:23,00 live births, Spain 1:12,000 live births, the Netherlands 1:8,700. Asia: Japan 1:51,000 live births and Taiwan 1:263,500 live births (Oerton J et al., 2005). These screenings are not flawless, and some individuals may go undetected due to the symptom onset nature of MCADD symptoms. Implementing neonatal newborn screening with tandem mass spectrometry, biochemical analysis, and genetic analysis will significantly reduce false negatives and reduce the risk impact of MCADD in undiagnosed carriers (Dietrich M., 2015).

Genetic testing could then be implemented to determine the pathogenic variant and aid in genetic counseling for future considerations. MCAD deficiency is inherited in an autosomal recessive manner. Symptomatic offspring must inherit a mutated allele from both parents. Siblings of an affected individual are at a 25% risk of being symptomatic, a 50% risk of being asymptomatic carriers, and a 25% risk of being unaffected and non-carriers. If one of the parents are also affected, the risk could be of being a symptomatic carrier would be 50% (Green N., 2011)

Treatment would be consulting a dietary plan with a dietitian.


Primary Research
Materials and Methods