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

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

During prolonged fasting or increased energy demands (e.g., fever, stress, or lack of sleep), energy production increasingly relies on fat metabolism. Deficiency of very long-chain acyl-CoA dehydrogenase (VLCAD) impairs energy production from fats and causes metabolic crisis, cardiomyopathy, muscle pain, or myoglobinuria. Phenotypes of VLCAD deficiency include "early," "childhood," and "adult." Sudden infant deaths may occur as a result of cardiac dysfunction or arrhythmia.

Clinical Characteristics

With treatment of VLCADD, risk of sudden death appears to be reduced.

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 may begin in adolescence or adulthood and may be triggered by prolonged exercise. Symptoms may be mild or severe.
  • Symptom onset <12 months of age
  • Muscle weakness and hypotonia
  • Hypertrophic cardiomyopathy
  • Respiratory distress
  • FTT/Feeding difficulties
Initial signs/symptoms of VLCADD in the early and childhood types may include:
  • Poor feeding
  • Vomiting
  • Diarrhea
  • Irritability
  • Behavior changes
  • Extreme sleepiness
  • Muscle weakness
  • Lethargy
  • Lab findings:
    • Metabolic acidosis
    • Hypoglycemia
If not treated promptly, patients may experience:
  • Hepatomegaly
  • Difficulty breathing
  • Muscle weakness with exertion
  • Arrhythmia
  • Cardiomyopathy
  • Seizures
  • Brain damage
  • Death
Adult type symptoms may include:
  • Muscle breakdown with exercise or prolonged fasting
  • Muscle aches
  • Weakness
  • Cramps
  • Reddish-brown urine
  • Kidney failure

Incidence

In the U.S., the incidence is about 1:63,000. [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.
  • Recommend frequent feeding (every 3 to 4 hours in infants), including at night.
  • Provide emergency treatment and referral for symptoms of hypoglycemia, arrhythmia, or cardiac decompensation.

Confirming the Diagnosis

  • To confirm the diagnosis of VLCADD, work with Newborn Screening Services (see RI providers [2]).
  • Follow-up testing may include quantitative plasma acylcarnitine profile, urine organic acids, mutation analysis of the VLCAD gene, enzyme assay in fibroblasts, and additional biochemical, genetic tests.

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.

Fatty Acid Oxidation Disorders (MCADD, LCHADD, VLCADD) (FAQ)
Answers to questions families often have about caring for their child with VLCADD.

After a Diagnosis or Problem is Identified
Families can face a big change when their baby tests positive for a newborn condition. Find information about A New Diagnosis - You Are Not Alone; Caring for Children with Special Health Care Needs; Assistance in Choosing Providers; Partnering with Healthcare Providers; Top Ten Things to Do After a Diagnosis.

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) (PDF Document 289 KB)
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

Support

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

General

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

ACT Sheet for VLCAD Deficiency (ACMG) (PDF Document 347 KB)
Contains short-term recommendations for clinical follow-up of the newborn who has screened positive; American College of Medical Genetics.

Confirmatory Algorithm for VLCAD Deficiency (ACMG) (PDF Document 45 KB)
https://www.acmg.net/PDFLibrary/C14-1-Elevated-Algorithm.pdf

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.

Authors & Reviewers

Initial publication: March 2007; last update/revision: December 2015
Current Authors and Reviewers:
Author: Nicola Longo, MD, Ph.D.

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

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