Handbook of Genetic Counseling/Medium-chain acyl-coenzyme A dehydrogenase Deficiency
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Medium-chain acyl-coenzyme A dehydrogenase Deficiency
- Medium-chain acyl-coenzyme A dehydrogenase (MCAD) is an enzyme involved in mitochondrial fatty acid b-oxidation (FAO). Fatty acid oxidation provides energy for peripheral tissues when glycogen is depleted through hepatic ketogenesis. A defect in the MCAD enzyme causes accumulation of medium-chain fatty acids, metabolized to glycine- and carnitine-esters and dicarboxylic acids, and hypoketonia.
- MCAD deficiency is caused by a mutation in the ACADM gene
- Chromosomal locus 1p31
- 31 known disease causing mutations
- 1 common mutation, K304E, accounts for 76% of alleles
- Common in Caucasians, especially with Northern European ancestry
- Disease incidence 1:4,900 to 1:17,000
- Carrier frequency 1:40 to 1:100
- Less common among Hispanics
- Rare in African-American, and Native-American populations
- Metabolic testing
- Symptomatic individuals should have plasma acylcarnitines, plasma fatty acids, urine organic acids, and urine acylclycines analyzed and interpreted.
- Enzymatic testing
- MCAD enzyme activity should be measured in fibroblasts or other tissues to confirm diagnosis
- Molecular testing
- Molecular genetic testing by mutation analysis (for K204E) or sequence analysis of the ACADM gene can confirm diagnosis
- Newborn screening
- MCAD is part of the newborn screening panel in 9 states (IA, ME, MA, NC, OH, SC, SD, WI, WY).
- Prenatal testing
- Enzymatic or molecular testing can be performed prenatally; however, there is limited benefit to prenatal vs. newborn testing.
- Carrier testing
- Only molecular testing can determine carrier status.
Clinical Features 
- Typical presentation includes hypoketotic hypoglycemia, vomiting, lethargy,
seizures, and coma precipitated by prolonged fasting or common illness.
- Hepatomegaly and acute liver disease may also be present.
- Sudden, unexplained death may be first symptom (18%).
Natural History 
- Typically normal at birth following uneventful pregnancy
- Most present with symptoms between 3 and 24 months in response to prolonged fasting or infection
- Initial presentation in adulthood also possible
- Affected individuals may lose developmental milestones or acquire aphasia or ADD as a result of acute metabolic event
- Individuals identified as newborns typically develop normally under treatment
- MCAD deficiency is an autosomal recessive disorder.
- Enzymatic and Molecular testing can confirm diagnosis.
- Both mutation and sequence analysis are available on a clinical basis.
Management & Treatment 
- MCAD is a highly treatable condition- good prognosis when managed
- Avoidance of fasting is key-
- Infants should be fed frequently
- Toddlers should be given 2 g/kg uncooked cornstarch before bed
- Low-fat diet and carnitine supplementation may be beneficial
Differential Diagnosis 
- Other disorders of acyl-CoA dehydrogenase (ACAD) gene family
- Other disorders of fatty acid b-oxidation
- Parental guilt over allowing too long of time between feedings which triggered onset of symptoms
- Parental guilt over passing gene to child
- When presenting symptom is sudden death, loss of seemingly healthy child can be devastating
- Parent or sibling may be identified as a homozygote during carrier testing
- Family planning- risk for future offspring/siblings of affected individual
Patient Resources 
- FOD (Fatty Oxidation Disorder) Family Support Group
- 805 Montrose Drive
- Greensboro, NC 27410
- Phone: (336) 547-8682
- Email: email@example.com
- Web: www.fodsupport.org
- Organic Acidemia Association
- 13210 35th Avenue North
- Plymouth, MN 55441
- Phone; (763) 556-1797
- Email: OAANews@aol.com
- Web: www.oaanews.org
- United Mitochondrial Disease Foundation
- 8085 Saltsburg Road, Suite 201
- Pittsburgh, PA 15239
- Phone: (412) 793-8077
- Email: firstname.lastname@example.org
- Web: www.umdf.org
The informaiton in this outline was last updated in Feb 2003.