55 Kenosia Avenue
Danbury, CT 06810
Phone: 203.744.0100
Toll Free: 1.800.999.6673

Medium Chain Acyl CoA Dehydrogenase Deficiency

The information in NORD’s Rare Disease Database is for educational purposes only. It should never be used for diagnostic or treatment purposes. If you have questions regarding a medical condition, always seek the advice of your physician or other qualified health professional. NORD’s reports provide a brief overview of rare diseases. For more specific information, we encourage you to contact your personal physician or the agencies listed as “Resources” on this report.

Copyright 1988, 1989, 1996, 1998, 2005

Synonyms of Medium Chain Acyl CoA Dehydrogenase Deficiency

Disorder Subdivisions

General Discussion

Medium chain acyl-CoA dehydrogenase (MCAD) deficiency is a rare genetic metabolic disorder characterized by a deficiency of the enzyme medium chain acyl-CoA dehydrogenase. This enzyme is found to be most active in the liver, certain white blood cells (leukocytes), and certain connective tissue cells (fibroblasts) and is necessary for the breakdown (oxidation) of certain fats (medium chain fatty acids). Failure to break down these fats can lead to the abnormal accumulation of fatty acids in the liver and the brain. Abnormally low levels of the MCAD enzyme may also hamper or interrupt other processes associated with the metabolism of fatty acids.

In infants with MCAD deficiency, symptoms may include recurrent episodes of unusually low levels of a certain sugar (glucose) in the blood (hypoglycemia), lack of energy (lethargy), vomiting, and/or liver malfunction. These symptoms are most frequently triggered when an affected infant does not eat for an extended period of time (fasting). In some cases, a viral illness (e.g., upper respiratory infection) that limits food intake may cause the symptoms to occur. MCAD deficiency is the most common disease in a group of disorders that involve abnormalities of fatty acid metabolism (fatty acid oxidation disorders [FODs]). MCAD deficiency is inherited as an autosomal recessive trait.


The symptoms of MCAD deficiency usually begin during infancy, most frequently between three to 15 months of age. However, in extremely rare cases, onset may not be until later in childhood. Infants with MCAD Deficiency usually appear normal until they go without eating for a period of 12 to 16 hours (fasting). The symptoms often follow mild infections such as middle ear infection (otitis media) or inflammation of the digestive tract (gastroenteritis).

Extended periods of time without food leads to an episode of low levels of a certain sugar (glucose) in the blood (hypoglycemia), lack of energy (lethargy), and vomiting. In severe episodes, coma, seizures, and life-threatening complications (e.g., severe metabolic acidosis) may ensue. In some cases, affected infants may not exhibit symptoms, such as lethargy or vomiting, between episodes of more severe symptoms (i.e., those brought on by fasting).

Infants with MCAD deficiency may also exhibit an abnormal accumulation of fat in the liver and brain, unusually high levels of ammonia in the blood (hyperammonemia), an abnormally large liver (hepatomegaly), and/or improper liver function (hepatic dysfunction). In addition, affected infants may exhibit low levels of a substance (carnitine) that carries fatty acids to the energy centers of muscles (mitochondria). Deficient levels of carnitine may lead to the accumulation of acidic wastes in the blood (organic acidemia).

Some severely affected infants may also have an abnormal accumulation of fluid around the brain (cerebral edema) that may lead to brain damage (encephalopathy). In some cases, as affected individuals age, other problems may develop. These may include delays in developmental milestones, such as learning to crawl, walk, and/or speak. In addition, some affected individuals may also experience behavioral problems (e.g., attention deficit hyperactivity disorder [ADHD]). (For more information on this disorder, choose "Attention Deficit Hyperactivity" as your search term in the Rare Disease Database.)

In very rare cases, individuals with MCAD deficiency may experience loss of speech (aphasia), muscle weakness (hypotonia), and/or failure to gain weight and grow at the expected rate (failure to thrive). The range and severity of symptoms may vary greatly from case to case. Some individuals may not exhibit symptoms (asymptomatic); others, even those within the same family, may develop serious, life-threatening complications.


MCAD deficiency is inherited as an autosomal recessive trait. Genetic diseases are determined by two genes, one received from the father and one from the mother.

Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%.

Most parents of children with MCAD deficiency have about half the normal level of the medium chain acyl-CoA dehydrogenase enzyme. However, these parents do not exhibit the symptoms of this disorder. Researchers believe that these parents are heterozygotes for the defective MCAD gene. Heterozygous is a condition in which a person has two different genes at the same place on matched chromosomes. An individual who is heterozygous for a particular trait has inherited a gene for that trait from one parent and the alternative gene from the other parent. An individual heterozygous for a hereditary disorder produced by a recessive gene will not show the disease or will have a milder form of it. The offspring of a heterozygous carrier of a genetic disorder will have a fifty percent chance of inheriting the gene dominant for the trait.

The gene that is responsible for regulating the production of the enzyme medium chain acyl-CoA dehydrogenase is thought to be located on the short arm (p) of chromosome 1 (1p). Chromosomes are found in the nucleus of all body cells. They carry the genetic characteristics of each individual. Pairs of human chromosomes are numbered from 1 through 22, with an unequal 23rd pair of X and Y chromosomes for males, and two X chromosomes for females. Each chromosome has a short arm designated as "p" and a long arm identified by the letter "q".

Symptoms of MCAD deficiency develop due to deficient levels of the enzyme medium chain acyl-CoA dehydrogenase, which is needed for the breakdown of medium chain fatty acids. Low levels of this enzyme interrupt fatty acid metabolism in the liver. Symptoms of MCAD Deficiency are triggered when an affected individual fails to eat for an extended period of time. In some cases, a viral illness (e.g., upper respiratory infection) that limits the intake of food may result in an episode of symptoms. Improper fatty acid metabolism may also lead to the abnormal accumulation of fatty acids in the liver and brain, causing these organs to function improperly.

The abnormal abundance of medium chain fatty acids may inhibit or affect several chemical processes in the body including the production of substances used by muscle and brain tissue for fuel (ketone bodies) and the formation of the blood sugar glucose (gluconeogenesis). If gluconeogenesis is hampered, it may contribute to the development of hypoglycemia. MCAD deficiency may also result in abnormally low levels of carnitine (carnitine deficiency). Carnitine deficiency may cause the accumulation of acidic wastes in the blood (organic acidemia). MCAD deficiency may also interrupt or hinder other chemical processes in the body.

There are several different allelic variants of MCAD deficiency. An allele is any of a series of two or more genes that may occupy the same position (locus) on a specific chromosome. Symptoms of these allelic variants of MCAD deficiency are essentially the same.

Affected Populations

MCAD deficiency is a rare metabolic disorder that affects males and females in equal numbers. More than 200 hundred cases have been reported in the medial literature. In the general population, it occurs in approximately 1 in 50,000 live births. In Americans of Northwestern European origin, it may occur in 1 in 6,400 to 1 in 46,000 individuals. In most cases, onset occurs during infancy, usually between the ages of 3 to 15 months. However, in some rare cases, symptoms may not become apparent until later in childhood.

Related Disorders

Symptoms of the following disorders are similar to those of MCAD deficiency. Comparisons may be useful for a differential diagnosis:

Reye syndrome is a rare childhood disorder characterized by low blood sugar (hypoglycemia), liver dysfunction, and/or brain damage (encephalopathy). Symptoms of Reye syndrome usually occur after a viral illness, such as upper respiratory infection, chickenpox, or influenza. Additional symptoms of Reye syndrome may include vomiting, lack of energy (lethargy), diarrhea, and/or an abnormally high rate of breathing. Affected infants eventually exhibit profound lethargy, confusion, irritability, and/or other behavioral changes. Severe cases may lead to seizures and, eventually, coma. In addition, infants with Reye syndrome may develop an accumulation of fluid around the brain (cerebral edema), liver dysfunction, and/or an abnormally large liver (hepatomegaly) due to the buildup of certain fats. The exact cause of Reye syndrome is not known. (For more information on this disorder, choose "Reye" as your search term in the Rare Disease Database.)

Glutaricaciduria II is an extremely rare inherited metabolic disorder. There are three forms of this type of glutaricaciduria: a severe form that is associated with defects present at birth (congenital anomalies); a milder form that does not have any major physical anomalies; and a milder form that has an onset later in life. The two forms with childhood onset are characterized by low levels of a certain sugar in the blood (hypoglycemia), abnormal accumulation of acidic wastes in the blood (organic acidemia), and/or the buildup of fat in the liver, kidney, and middle layer of the heart wall (myocardium). Congenital anomalies associated with the severe form include multiple cysts on the kidneys, diminished muscle tone (hypotonia), and/or malformation of the roof of the mouth (palate). The late-onset form of glutaricaciduria (ethylmalonic gdipicaciduria) is characterized by low levels of blood sugar (hypoglycemia), lack of energy (lethargy), diminished muscle tone (hypotonia), an abnormally large liver (hepatomegaly), and/or the abnormal accumulation of fat in the liver. In addition, this form of glutaricaciduria exhibits a buildup of certain compounds in the urine including dicarboxylic acids. All three forms of glutaricaciduria II are inherited as autosomal recessive traits. (For more information on this disorder, choose "Glutaricaciduria II" as your search term in the Rare Disease Database.)

Fatty acid oxidation disorders (FODs) are a group of genetic metabolic disorders that are characterized by the abnormal accumulation of fatty acids in the body. In these disorders, the body fails to break down (metabolize) complex molecules into simpler molecules. As a result, affected individuals cannot use fats for energy. Stored fat is the secondary energy source for the body (the first is glucose). When glucose runs out, the body converts stored fat for energy. The inability to break down fatty acids results in their abnormal accumulation within the body, potentially affecting any organ system of the body. Thus, the symptoms of FODs vary widely even among members of the same family. The FODs encompass many different disorders including MCAD, very long chain acyl-CoA dehydrogenase (VLCAD), short chain acyl-coA dehydrogenase (SCAD) deficiency, and the primary carnitine defiency syndromes. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)

Very-long-chain acyl-CoA dehydrogenase deficiency (VLCAD) is yet another rare inherited metabolic disorder of fat metabolism, or FOD. It affects infants and is caused by a deficiency of the enzyme known as very-long-chain CoA dehydrogenase. The symptoms of this disorder are similar to, but more severe than, those of medium-chain acyl-CoA dehydrogenase deficiency (MCAD). Characteristic signs usually appear shortly after birth and include recurrent episodes of low blood glucose levels (hypoglycemia), vomiting, and/or coma after periods of low food consumption. Muscle weakness, heart disease due to enlargement of the muscles of the heart (hypertrophic cardiomyopathy), and/or an enlarged liver (hepatomegaly) may also occur. Other symptoms may include abnormally high levels of acids in the urine, abnormally low levels of the amino acid carnitine in muscle tissue (secondary carnitine deficiency), and/or abnormal liver function test results.

Primary carnitine deficiency syndromes are a rare group of disorders characterized by abnormally low levels of a substance (carnitine) that carries fatty acids to the energy centers of muscles (mitochondria). Symptoms of these disorders may include extreme muscle weakness, abnormally low levels of a certain sugar (glucose) in the blood (hypoglycemia), and/or liver, heart, and/or central nervous system complications. In addition, affected individuals may experience vomiting, confusion, lack of energy (lethargy), and, in severe cases, coma. Carnitine deficiency may cause an abnormal accumulation of acidic wastes in the blood (organic acidemia). (For more information on these disorders, choose "Carnitine Deficiency Syndromes" as your search terms in the Rare Disease Database.)

Standard Therapies

MCAD deficiency may be diagnosed before birth (prenatally) by a specialized test called amniocentesis. During amniocentesis, a sample of the fluid around the fetus is removed and studied. Such studies can reveal dramatically reduced activity of the medium chain acyl-CoA dehydrogenase enzyme.

An acylcarnitine profile test is often used to diagnose infants with MCAD deficiency. During this test, blood or tissue samples are taken and studied to detect and analyze acylcarnitine, a substance that builds up in individuals with fatty acid oxidation disorders such as MCAD deficiency. Each FOD has a unique acylcarnitine profile.

Additional diagnostic tests include enzyme tests (assays) on cultured white blood cells (leukocytes), blood plasma, and certain connective tissue cells (fibroblasts) that may reveal reduced activity of the medium chain acyl-CoA dehydrogenase enzyme. Another diagnostic procedure is urinary analysis, which may reveal excess levels of certain compounds (e.g., suberylglycine and phenylpropionylglycine) in the urine as well as abnormally high levels of dicarboxylic acid, especially during a hypoglycemic episode. Amplication refractory mutation system (ARMS) along with organic acid analysis may also be used to diagnose MCAD Deficiency.

The earlier the diagnosis is made and treatment initiated, the lower the chances become that an infant with MCAD Deficiency will exhibit developmental disabilities. In addition, all siblings of children with MCAD deficiency should be tested immediately to determine whether they have the disorder.

Preventive measures should be taken to ensure that affected individuals do not go without food for extended periods of time (12 to 16 hours). These measures may include awakening a child at night for feeding (e.g., intravenous or parental). A low-fat diet may be of benefit to some people with MCAD deficiency. During periods of fasting, oral cornstarch may be used to prevent hypoglycemia. During episodes of hypoglycemia, intravenous fluids containing 10 percent dextrose should be administered promptly. Glycine or oral carnitine may also be administered to build up carnitine levels in the body.

Genetic counseling will be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive. A team approach for infants with this disorder may be of benefit and may include special social support and other medical services.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov.

For information about clinical trials sponsored by private sources, contact:

Medium Chain Acyl CoA Dehydrogenase Deficiency Resources

NORD Member Organizations:

(To become a member of NORD, an organization must meet established criteria and be approved by the NORD Board of Directors. If you're interested in becoming a member, please contact Susan Olivo, Membership Manager, at solivo@rarediseases.org.)

Other Organizations:


Roe CR. Medium-Chain Acyl-CoA Dehydrogenase Deficiency. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:437-8.

Behrman RE., ed. Nelson Textbook of Pediatrics, 15th ed. Philadelphia, PA: W.B. Saunders Company; 1996: 336.

Scriver CR, et al., eds. The Metabolic and Molecular Basis of Inherited Disease. 7th Ed. New York, NY; McGraw-Hill Companies, Inc; 19951515-22.

Menkes JH., au., Pine JW, et al., eds. Textbook of Child Neurology, 5th ed. Baltimore, MD: Williams & Wilkins; 1995:71.

Buyce ML., ed. Birth Defects Encyclopedia. Dover, MA: Blackwell Scientific Publications; For: The Center for Birth Defects Information Services Inc; 1990:53-5.

Lee PJ, et al., L-carnitine and exercise tolerance in medium-chain acyl-coenzyme A dehydrogenase defiency (MCAD) deficieny: a pilot study. J Inherit Metab Dis. 2005;28:141-52.

Solis JO, Singh RH. Management of fatty acid oxidation disorders: a survey of current treatment strategies. J Am Diet Assoc. 2002;102:1800-3.

Felliet F, et al., Adult presentation of MCAD deficiency revealed by coma and severe arrhythmias. Intensive Care Med. 2003;29:1594-7.

Christodoulou J, et al., Neonatal onset of medium-chain acyl-coenzyme A dehydrogenase deficiency with confusing biochemical features. J Pediatr. 1995;126:65-8.

Iafolla AK, et al., Medium-chain acyl-coenzyme A dehydrogenase deficiency: clinical course in 120 affected children. J Pediatr. 1994;124:409-15.

Rinaldo P, et al. Effect of treatment with glycine and L-carnitine in medium-chain acyl-coenzyme A dehydrogenase deficiency. J Pediatr. 1993;122:580-4.

Smith Jr. ET, et al., Medium-chain acylcoenzyme-A dehydrogenase deficiency. Not just another Reye syndrome. Am J Forensic Med Pathol. 1993;14:313-8.

Van Hove JL, et al., Medium-chain acyl-CoA dehydrogenase (mcad) deficiency: diagnosis by acylcarnitine analysis in blood. Am J Hum Genet. 1993;52:958-66.

Wilcken B, et al., Neonatal symptoms in medium-chain acyl coenzyme A dehydrogenase deficiency. Arch Dis Child. 1993;69:292-4.

Tsai MY, et al., Laboratory diagnosis of medium-chain acyl-coenzyme A dehydrogenase deficiency by the amplication refractory mutation system. Clin Chem. 1993;39:280-3.

McKusick VA., ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:607008; Last Update:7/29/2003. Available at: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=607008 Accessed On: May 20, 2005.

Roth KS. Medium-Chain Acyl-CoA Dehydrogenase Defiency. eMedicine Journal. 2002;3:9pp. Available at:
http://www.emedicine.com/ped/topic1392.htm Accessed On: May 20, 2005

Report last updated: 2008/04/11 00:00:00 GMT+0