Rare Endocrinology News

Disease Profile

VLCAD deficiency

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 100 000

3,310 - 29,790

US Estimated

1-9 / 100 000

5,135 - 46,215

Europe Estimated

Age of onset

Infancy

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ICD-10

E71.3

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Very long-chain acyl-CoA dehydrogenase deficiency; VLCADD

Categories

Congenital and Genetic Diseases; Heart Diseases; Metabolic disorders;

Summary

VLCAD deficiency is a condition in which the body is unable to properly breakdown certain fats (called very long-chain fatty acids) into energy, particularly during periods without food (fasting). Signs and symptoms can occur during infancy, childhood or adulthood depending on the form of the condition and may include low blood sugar (hypoglycemia), lack of energy, and muscle weakness. Children affected by the most severe forms of the condition are also at risk of serious complications such as liver abnormalities and life-threatening heart problems. VLCAD deficiency is caused by changes (mutations) in the ACADVL gene and is inherited in an autosomal recessive manner. Treatment is based on the signs and symptoms present in each person.[1][2][3]

Symptoms

There are three forms of VLCAD deficiency: a severe, early-onset form; a hepatic (liver) or hypoketotic hypoglycemic form; and a later-onset episodic myopathic form.[1]

Signs and symptoms of the severe, early-onset form occur in the first few months of life and include cardiomyopathy (heart disease), pericardial effusion (fluid around the heart), heart arrhythmias (abnormal heart beat), low muscle tone, enlarged liver, and intermittent hypoglycemia (low blood sugar). The heart problems can be life threatening, but are often improved with early treatment and diet modifications.[1][2]

People affected by the hepatic or hypoketotic hypoglycemic form typically develop symptoms during early childhood. These features may include hypoketotic hypoglycemia and enlarged liver (without cardiomyopathy). "Hypoketotic" refers to a low level of ketones, which are produced during the breakdown of fats and used for energy. Hypoglycemia refers to low blood sugar. Together, these signs are called "hypoketotic hypoglycemia."[1]

The episodes of hypoglycemia seen in the early-onset form and hepatic/hypoketotic hypoglycemia form can cause a child to feel weak, shaky and/or dizzy with clammy, cold skin. If not treated, it can lead to coma, and possibly death. Periods of hypoglycemia can also occur with other symptoms as part of a metabolic crisis.[4]

Signs and symptoms of the later-onset episodic myopathic form may include intermittent rhabdomyolysis (breakdown of muscle), muscle cramps, muscle pain, and exercise intolerance. It is the most common form of VLCAD deficiency.[1]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
30%-79% of people have these symptoms
Increased circulating free fatty acid level
0030781
5%-29% of people have these symptoms
Elevated hepatic transaminase
High liver enzymes
0002910
Elevated serum creatine kinase
Elevated blood creatine phosphokinase
Elevated circulating creatine phosphokinase
Elevated creatine kinase
Elevated serum CPK
Elevated serum creatine phosphokinase
High serum creatine kinase
Increased CPK
Increased creatine kinase
Increased creatine phosphokinase
Increased serum CK
Increased serum creatine kinase
Increased serum creatine phosphokinase

[ more ]

0003236
Episodic tachypnea
0002876
Exercise-induced rhabdomyolysis
0009045
Feeding difficulties
Feeding problems
Poor feeding

[ more ]

0011968
Hepatomegaly
Enlarged liver
0002240
Hypoketotic hypoglycemia
0001985
Hypothermia
Abnormally low body temperature
0002045
Jaundice
Yellow skin
Yellowing of the skin

[ more ]

0000952
Overweight
0025502
Patent foramen ovale
0001655
Respiratory distress
Breathing difficulties
Difficulty breathing

[ more ]

0002098
Small for gestational age
Birth weight less than 10th percentile
Low birth weight

[ more ]

0001518
Ventricular septal defect
Hole in heart wall separating two lower heart chambers
0001629
1%-4% of people have these symptoms
Anteriorly placed anus
0001545
Atrioventricular block
Interruption of electrical communication between upper and lower chambers of heart
0001678
Dilated cardiomyopathy
Stretched and thinned heart muscle
0001644
Enlarged cisterna magna
0002280
Hyperammonemia
High blood ammonia levels
0001987
Hypocalcemia
Low blood calcium levels
0002901
Hypoproteinemia
Decreased protein levels in blood
0003075
Infantile muscular hypotonia
Decreased muscle tone in infant
0008947
Inflammatory abnormality of the skin
Skin inflammation
0011123
Lethargy
0001254
Macrocephaly
Increased size of skull
Large head
Large head circumference

[ more ]

0000256
Metabolic acidosis
0001942
Muscle spasm
0003394
Obesity
Having too much body fat
0001513
Pain
0012531
Pericardial effusion
Fluid around heart
0001698
Pneumonia
0002090
Prolonged QT interval
0001657
Ventricular fibrillation
0001663
Ventricular tachycardia
0004756
Vomiting
Throwing up
0002013

Cause

VLCAD deficiency is caused by changes (mutations) in the ACADVL gene. This gene encodes an enzyme that is required for the proper break down (metabolism) of a certain group of fats called very long-chain fatty acids. Mutations in the ACADVL gene lead to reduced levels of this enzyme which prevents the proper metabolism of these fats. Because very long-chain fatty acids are an important source of energy, particularly for the heart and muscles, this may result in certain symptoms such as lethargy and hypoglycemia. Fats that are not properly broken down can also build-up and damage tissues such as the heart, liver, and muscles, which can cause the other features seen in people with VLCAD deficiency.[3][1][4]

Diagnosis

A diagnosis of VLCAD deficiency may be suspected based on an abnormal newborn screen or the presence of characteristic signs and symptoms. In both of these cases, additional testing can then be ordered to further investigate the diagnosis. This testing may include specialized tests performed on a sample of blood, urine, skin cells, muscle, and/or liver tissue. Genetic testing for changes (mutations) in the ACADVL gene can confirm the diagnosis.[1][2]

GeneReview's Web site offers more specific information about the diagnosis of VLCAD deficiency. Please click on the link to access this resource.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Newborn Screening

    • An ACTion (ACT) sheet is available for this condition that describes the short-term actions a health professional should follow when an infant has a positive newborn screening result. ACT sheets were developed by experts in collaboration with the American College of Medical Genetics.
    • An Algorithm flowchart is available for this condition for determining the final diagnosis in an infant with a positive newborn screening result. Algorithms are developed by experts in collaboration with the American College of Medical Genetics.
    • Baby's First Test is the nation's newborn screening education center for families and providers. This site provides information and resources about screening at the local, state, and national levels and serves as the Clearinghouse for newborn screening information.
    • National Newborn Screening and Global Resource Center (NNSGRC) provides information and resources in the area of newborn screening and genetics to benefit health professionals, the public health community, consumers and government officials.

      Treatment

      Management of VLCAD deficiency depends on many factors, including the form of the condition and the specific signs and symptoms present. For example, people affected by the severe forms of the condition are typically placed on a low-fat, high-carbohydrate diet with frequent meals. Supplemental calories may be provided through medium-chain triglycerides (MCT oil). If hospitalization is necessary for acute episodes of hypoglycemia and/or metabolic crisis, intravenous glucose may be administered as an energy source. Periods of rhabdomyolysis may be treated with hydration and alkalization of the urine (decreasing the amount of acid you take in) to protect kidney function and to prevent acute kidney failure. Affected people are generally advised to avoid fasting, dehydration, and a high-fat diet.[1][2]

      Management Guidelines

      • Orphanet Emergency Guidelines is an article which is expert-authored and peer-reviewed that is intended to guide health care professionals in emergency situations involving this condition.

        Organizations

        Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

        Organizations Supporting this Disease

          Organizations Providing General Support

            Learn more

            These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

            Where to Start

            • Genetics Home Reference (GHR) contains information on VLCAD deficiency. This website is maintained by the National Library of Medicine.
            • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.
            • The Screening, Technology And Research in Genetics (STAR-G) Project has a fact sheet on this condition, which was written specifically for families that have received a diagnosis as a result of newborn screening. This fact sheet provides general information about the condition and answers questions that are of particular concern to parents.

              In-Depth Information

              • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
              • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
              • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
              • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
              • PubMed is a searchable database of medical literature and lists journal articles that discuss VLCAD deficiency. Click on the link to view a sample search on this topic.

                References

                1. Nancy D Leslie, MD, C Alexander Valencia, PhD, Arnold W Strauss, MD, Jessica Connor, MS, and Kejian Zhang, MD, MBA. Very Long-Chain Acyl-Coenzyme A Dehydrogenase Deficiency. GeneReviews. September 2014; https://www.ncbi.nlm.nih.gov/books/NBK6816/.
                2. Very Long Chain Acyl CoA Dehydrogenase Deficiency (LCAD). NORD. 2013; https://rarediseases.org/rare-diseases/very-long-chain-acyl-coa-dehydrogenase-deficiency-lcad/.
                3. VLCAD deficiency. Genetics Home Reference Web site. 11/2009; https://ghr.nlm.nih.gov/condition/very-long-chain-acyl-coa-dehydrogenase-deficiency.
                4. Very long chain acyl-CoA dehydrogenase. STAR-G. July 2013; https://www.newbornscreening.info/Parents/fattyaciddisorders/VLCADD.html#3.

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