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Very Long-Chain Acyl-CoA Dehydrogenase Deficiency (VLCADD)

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Guidance for primary care clinicians receiving a positive newborn screen result

Other Names

ACADVL deficiency
VLCAD deficiency

ICD-10 Coding

E71.310, Long chain/very long chain acyl CoA dehydrogenase deficiency

Disorder Category

A fatty acid oxidation disorder

Screening

Abnormal Finding

Elevated C14:1 +/- (acylcarnitine)

Tested By

Tandem mass spectrometry (MS/MS); sensitivity and specificity unknown [Ficicioglu: 2010]

Description

Very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) impairs energy production from fat sources within the body. Metabolic stress, when energy production relies on fat metabolism, can cause a metabolic crisis, presenting with rhabdomyolysis, hypoketotic hypoglycemia, and cardiomyopathy. Common triggers include prolonged fasting, infectious illnesses, fever, or excessive physical activity. There is considerable variability in severity recognized with VLCAD deficiency, ranging from a severe early-onset form with neonatal multiorgan failure to the later-onset form with isolated episodic myopathy. Sudden infant deaths may occur as a result of cardiac dysfunction or arrhythmia.

Clinical Characteristics

With treatment of VLCADD, the risk of sudden death is reduced. Additionally, a fat-restricted diet and medium-chain triglyceride supplementation can reduce the risk of metabolic crises and preserve cardiac and muscle strength.
Without treatment, sudden cardiac death is common in the early childhood form. Symptoms of VLCADD with early onset may begin between birth and 4 months of age. Childhood onset may begin in later infancy or early childhood, especially after fasting or illness. Adult onset, beginning from adolescence to late adulthood, is often triggered by prolonged physical activity. Symptoms may be mild or severe. Initial signs and symptoms depend on the subtype/severity.
Severe early-onset:
  • Symptom onset <12 months of age
  • Muscle weakness and hypotonia
  • Hypertrophic or dilated cardiomyopathy
  • Arrhythmias
  • Failure to thrive
  • Poor feeding/vomiting
  • Hypoketotic hypoglycemia
  • Lethargy
  • Multiorgan failure
Childhood-onset:
  • Hypoketotic hypoglycemia
  • Hepatomegaly
  • Muscle weakness
  • Arrhythmia
Late-onset:
  • Exercise intolerance
  • Muscle cramps
  • Intermittent rhabdomyolysis
  • Reddish-brown urine (myoglobinuria)
  • Acute kidney injury

Incidence

The incidence of VLCAD has risen since it was incorporated into newborn screening programs, with the identification of milder cases. More recent estimates suggest an incidence of 1:30,000 to 1:100,000 births. [Leslie: 2019] [Therrell: 2014]

Inheritance

Autosomal recessive

Primary Care Management

Next Steps After a Positive Screen

  • Contact the family and evaluate the infant for poor feeding, lethargy, hypotonia, hepatomegaly, or cardiac problems. Even mildly ill infants should receive immediate interventions including IV glucose.
  • Provide emergency treatment and referral for symptoms of hypoglycemia, arrhythmia, or cardiac decompensation.
  • Recommend frequent feeding (at least every 3 hours in newborns), including at night.

Confirming the Diagnosis

If the Diagnosis is Confirmed

Resources

Information & Support

Related Portal Content
VLCADD
Assessment and management information for the primary care clinician caring for the child with VLCAD deficiency.

For Professionals

VLCADD (GeneReviews)
Clinical characteristics, diagnosis/testing, management, genetic counseling, and molecular pathogenesis; from the University of Washington and the National Library of Medicine.

VLCADD (OMIM)
Information about clinical features, diagnosis, management, and molecular and population genetics; Online Mendelian Inheritance in Man, authored and edited at the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine

Communicating Newborn Screening Results to Families (ACHDNC)
One-page guide to help clinicians effectively communicate positive newborn screening results to parents; Advisory Committee on Heritable Disorders in Newborns and Children.

For Parents and Patients

VLCADD - 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 a newborn disorder; Screening, Technology and Research in Genetics.

Very long-chain acyl-CoA dehydrogenase deficiency (MedlinePlus)
Information for families that includes description, frequency, causes, inheritance, other names, and additional resources; from the National Library of Medicine.

Resources for VLCAD Deficiency (Disease InfoSearch)
Compilation of information, articles, research, case studies, and genetics links; from Genetic Alliance.

Tools

RI ACT Sheet for VLCADD (PDF Document 139 KB)
Provides recommendations for clinical and laboratory follow-up of the newborn with out-of-range screening results, along with national and local resources for clinicians and families; American College of Medical Genetics.

Confirmatory Algorithm for VLCADD (ACMG) (PDF Document 164 KB)
An algorithm of the basic steps involved in determining the final diagnosis of an infant with a positive newborn screen; American College of Medical Genetics.; American College of Medical Genetics.

Very Long Chain Acyl-CoA Dehydrogenase Deficiency (VLCADD) (NECMP)
A guideline for health care professionals treating the sick infant or child with VLCADD; 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.

Services for Patients & Families in Rhode Island (RI)

For services not listed above, browse our Services categories or search our database.

* number of provider listings may vary by how states categorize services, whether providers are listed by organization or individual, how services are organized in the state, and other factors; Nationwide (NW) providers are generally limited to web-based services, provider locator services, and organizations that serve children from across the nation.

Studies

Very Long Chain Acyl-CoA Dehydrogenase Deficiency (birth-17 years) (ClinicalTrials.gov)
Studies looking at better understanding, diagnosing, and treating this condition; from the National Library of Medicine.

Helpful Articles

PubMed search for VLCADD and neonatal screening, last 5 years.

Authors & Reviewers

Initial publication: March 2007; last update/revision: November 2023
Current Authors and Reviewers:
Author: Brian J. Shayota, MD, MPH
Reviewer: Nancy C. Rose, MD
Authoring history
2023: update: Brian J. Shayota, MD, MPHA
2023: update: Brian J. Shayota, MD, MPHA
2015: first version: Nicola Longo, MD, Ph.D.A
AAuthor; CAContributing Author; SASenior Author; RReviewer

Page Bibliography

Ficicioglu C, Coughlin CR 2nd, Bennett MJ, Yudkoff M.
Very long-chain acyl-CoA dehydrogenase deficiency in a patient with normal newborn screening by tandem mass spectrometry.
J Pediatr. 2010;156(3):492-4. PubMed abstract

Leslie ND, Valencia CA, Strauss AW, Zhang K.
Very Long-Chain Acyl-Coenzyme A Dehydrogenase Deficiency.
GeneReviews®. 2019. 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