MCADD

Other Names

Medium chain acyl-CoA dehydrogenase deficiency

ACADM

MCADH

Diagnosis Coding

E71.311, medium chain acyl CoA dehydrogenase deficiency

Disorder Category

A fatty acid oxidation disorder

Screening

Finding

Elevated C8 (octanoylcarnitine) with lesser elevations of C6 (hexanoylglycine) and C10:1 (decenoyl carnitine)

Tested By

Tandem mass spectrometry (MS/MS); sensitivity=100%; specificity=99.98% [Schulze: 2003]

Overview

Medium chain acyl-CoA dehydrogenase deficiency (MCADD) is one of several enzymes involved in the beta-oxidation of fatty acids within mitochondria. MCADD impairs hepatic ketogenesis, resulting in hypoketotic hypoglycemia during periods of prolonged fasting or increased energy demands (e.g., during acute illness or fever).

Prevalence

Prevalence is about 1:17,759 live births; it is most common in northern Europeans and US Caucasians. [Therrell: 2014]

Inheritance

Autosomal recessive

Prenatal Testing

Amniocentesis or chorionic villous sampling (CVS) for DNA testing

Clinical Characteristics

With treatment, prognosis is excellent. Without treatment, episodes of hypoketotic hypoglycemic accompanied by lethargy and vomiting may lead to seizures, coma, cardiac arrest, and death. Symptoms can appear shortly after birth (sometimes just after hospital discharge) or at time of acute illness, which prevents the child from eating or causes increasing energy expenditure (fever). Some affected individuals do not present until adulthood.

Initial symptoms/signs may include:
  • Poor feeding
  • Vomiting
  • Lethargy progressing to coma
  • Lab findings:
    • Hyperammonemia
    • Hypoglycemia
    • Elevated ALT and AST
Subsequent symptoms/signs may include:
  • Hepatomegaly
  • Liver dysfunction
  • Seizures
  • Encephalopathy
  • Sudden death

Follow-up Testing after Positive Screen

Quantitative plasma acylcarnitine profile, urine acylglycine (increased hexanoylglycine), urine organic acids - diagnosis is confirmed by DNA analysis

Primary Care Management

Upon Notification of the + Screen

  • Contact the family and evaluate the infant for related symptoms.
  • Provide emergency treatment and referral for symptoms of hypoglycemia, lethargy, and feeding problems.
  • Make sure the child eats at regular intervals (every 3 to 4 hours) and formula is available to the family in case breastfeeding becomes insufficient.
  • Confirm the diagnosis, work with the following service(s): see all Newborn Screening Programs services providers (3) in our database.
  • Evaluate and continue ongoing collaborative management, consult the following service(s): Pediatric Medical Genetics , (801-213-3599); See also Services below.

If the Diagnosis is Confirmed

  • Educate the family about signs, symptoms, the need for frequent feedings, and the need for urgent care if the infant becomes ill. (See MCADD - Information for Parents (STAR-G) for additional information.)
  • Provide an "emergency" letter guiding caregivers in the appropriate response to acute illness and a medical ID bracelet for older kids and adults.
  • Consider a heart-healthy diet for affected children after 1 year of age.
  • Consider oral L-carnitine, which may be recommended in case of deficiency.
  • Assist in management of irreversible consequences as necessary, particularly with developmental and educational interventions.
  • See the Portal’s diagnosis and management module for MCADD.

Specialty Care Collaboration

A dietician may work with the family to devise an optimal approach to dietary management.

Resources

Information & Support

For Professionals

MCADD - Information for Professionals (STAR-G)
Structured list of information about the condition and links to more information; Screening, Technology, and Research in Genetics.

MCADD (GeneReviews)
Excellent review of MCADD that includes a clinical description, differential diagnoses, management information, and molecular genetic information; by Detrich Matern, MD and Piero Rinaldo, MD, PhD - sponsored by the U.S. National Library of Medicine.

Utah Newborn Screening Program (UDOH)
Provides information about the program, related legislation, training for practices, and newborn conditions; Utah Department of Health.

Genetics in Primary Care Institute (AAP)
The goal of this site is to increase collaboration in the care of children with known or suspected genetic disorders. Includes health supervision guidelines and other useful resources; a collaboration among the Health Resources & Services Administration, the Maternal and Child Health Bureau, and the American Academy of Pediatrics.

For Parents and Patients

MCADD - Information for Parents (STAR-G)
A fact sheet, written by a genetic counselor and reviewed by metabolic and genetic specialists, for families who have received an initial diagnosis of this newborn disorder; Screening, Technology and Research in Genetics.

MCADD (Genetics Home Reference)
Excellent, detailed review of MCADD for patients and families; sponsored by the U.S. National Library of Medicine.

MCADD: A Guide for Parents (PacNoRGG) (PDF Document 618 KB)
Eight-page guide that includes an overview, social concerns, sample treatment plan, glossary, regional resources, and references; sponsored by the Pacific Northwest Regional Genetics Group.

MCADD: A Guide for Parents (PacNoRGG) (Spanish) (PDF Document 202 KB)
Spanish translation of an 8-page guide that includes an overview, social concerns, sample treatment plan, glossary, regional resources, and references; sponsored by the Pacific Northwest Regional Genetics Group.

Fatty Oxidation Disorders (FOD) Family Support Group
Information for families about fatty acid oxidation disorders, support groups, coping, finances, and links to other sites.

Newborn Screening Information for Clinicians (NNSGRC)
Fact sheets, data reports, publications ,and information for clinicians about genetic screening that includes links to state genetic contacts; National Newborn Screening & Global Resource Center.

Tools

ACT Sheet for MCADD (ACMG) (PDF Document 348 KB)
Contains short-term recommendations for clinical follow-up of the newborn who has screened positive; American College of Medical Genetics.

Confirmatory Algorithm for MCADD (ACMG) (PDF Document 63 KB)
Resource for clinicians to help confirm diagnosis; American College of Medical Genetics.

MCADD Acute Illness Protocol (NECMP) (PDF Document 17 KB)
Guideline for clinicians treating the sick infant or child who has MCADD; developed under the direction of Dr. Harvey Levy, Senior Associate in Medicine/Genetics at Children’s Hospital Boston, and Professor of Pediatrics at Harvard Medical School, for the New England Consortium of Metabolic Programs. Click pdf to view the complete protocol.

Services

Genetics-related clinical services throughout the world can be found through Genetics Clinic Directory (GeneTests).

Newborn Screening Programs

See all Newborn Screening Programs services providers (3) in our database.

Pediatric Genetics

See all Pediatric Genetics services providers (5) in our database.

For other services related to this condition, browse our Services categories or search our database.

Helpful Articles

PubMed search for MCADD in children, last 3 years.

Leonard JV, Dezateux C.
Newborn screening for medium chain acyl CoA dehydrogenase deficiency.
Arch Dis Child. 2009;94(3):235-8. PubMed abstract

Authors

Author: Nicola Longo, MD, PhD - 12/2015
Content Last Updated: 12/2015

Page Bibliography

Schulze A, Lindner M, Kohlmuller D, Olgemoller K, Mayatepek E, Hoffmann GF.
Expanded newborn screening for inborn errors of metabolism by electrospray ionization-tandem mass spectrometry: results, outcome, and implications.
Pediatrics. 2003;111(6 Pt 1):1399-406. PubMed abstract

Therrell BL Jr, Lloyd-Puryear MA, Camp KM, Mann MY.
Inborn errors of metabolism identified via newborn screening: Ten-year incidence data and costs of nutritional interventions for research agenda planning.
Mol Genet Metab. 2014;113(1-2):14-26. PubMed abstract / Full Text