VLCADD

Overview

Very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) is a disorder of long-chain fatty acid oxidation. During periods of prolonged fasting or increased energy demands (e.g., fever, stress, or gastroenteritis), energy production increasingly relies on the catabolism of fat stores. Deficiency of the enzyme, very long-chain acyl-CoA dehydrogenase (VLCAD), impairs energy production from fats and causes metabolic crisis, cardiomyopathy, muscle pain, and/or myoglobinuria. VLCAD deficiency can be classified as severe early-onset form, hepatic form - a milder form usually presenting in early childhood, or a late-onset myopathic form.

The early-onset (infantile) form, associated with a nearly complete absence of the enzyme, is characterized by dilated or hypertrophic cardiomyopathy, arrhythmia, hypotonia, hepatomegaly, hypoglycemia, and high morbidity and mortality, usually shortly after birth. The childhood form is milder, with hypoketotic hypoglycemia similar to MCAD (medium-chain acyl-CoA dehydrogenase) deficiency, with increased values of liver function tests and elevated creatine kinase. Stress usually triggers symptoms; cardiomyopathy can be seen. The mildest form is the late-onset variant, with exercise or fasting-induced rhabdomyolysis resembling the muscle form of carnitine palmitoyl transferase 2 (CPT2) deficiency. Sudden death may occur as a result of cardiac conduction abnormalities in any of the 3 types.

Other Names & Coding

ACADVL deficiency
Very long-chain acyl-CoA dehydrogenase deficiency
VLCAD deficiency
ICD-10 coding

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

Further coding details can be found at ICD-10 for Long-Chain/Very Long-Chain Acyl-CoA Dehydrogenase Deficiency (icd10data.com).

Prevalence

In the United States, the incidence is about 1:63,481. [Therrell: 2014]

Genetics

VLCADD is inherited in an autosomal recessive pattern. Genetic testing (DNA sequencing and deletion/duplication analysis) should be performed if an individual is symptomatic or if there is a positive newborn screening result. VLCADD results from mutations in the ACADVL gene, which codes for very long-chain acyl-CoA dehydrogenase, the first enzyme in the breakdown of long chain (14-20 carbons) fatty acids. Some mutations lead to a complete lack of enzyme activity, and these are associated with the infantile form. Other mutations allow for residual enzyme activity and are associated with child or adult forms. [Leslie: 2019] Prenatal DNA testing in cells obtained by amniocentesis or chorionic villous sampling (CVS) is available. [Leslie: 2019]

Prognosis

Except for infantile forms that can cause severe morbidity and mortality, the prognosis is excellent if the disease is identified before the first decompensation occurs. [Rovelli: 2019]

Practice Guidelines

Arnold GL, Van Hove J, Freedenberg D, Strauss A, Longo N, Burton B, Garganta C, Ficicioglu C, Cederbaum S, Harding C, Boles RG, Matern D, Chakraborty P, Feigenbaum A.
A Delphi clinical practice protocol for the management of very long chain acyl-CoA dehydrogenase deficiency.
Mol Genet Metab. 2009;96(3):85-90. PubMed abstract / Full Text

Roles of the Medical Home

Although all patients with VLCAD deficiency should be followed in the metabolic clinic, the medical home clinician will need to help with ongoing management and education, including:
  • Educate the family about the signs and symptoms of illness that would require urgent care.
  • Assist with the implementation of a low-fat diet supplemented with medium-chain triglycerides, if necessary.
  • Consider oral L-carnitine and medium-chain triglyceride (MCT) oil supplements.
  • Assist in the management of irreversible consequences as necessary, particularly with developmental and educational interventions.
  • Coordinate care with a dietician and pediatric geneticist when needs arise.

Clinical Assessment

Pearls & Alerts for Assessment

Upon notification of a positive screen

When the primary care clinician receives the notification of a positive newborn screen for VLCADD, the clinician should:

  1. Contact the family.
  2. Evaluate the infant for poor feeding, lethargy, hypotonia, hepatomegaly, or cardiac problems.
  3. Provide emergency treatment and referral for symptoms of hypoglycemia, arrhythmia, or cardiac decompensation.
  4. Work with the local newborn screening program to confirm the diagnosis through further testing and begin management.
VLCADD provides further immediate management information.

Normal physical exam

Unless a decompensation has occurred, the exam is entirely normal in most children.

Emergency treatment: DO NOT provide intralipid

A patient with VLCAD should have a letter that details an individualized plan in case of emergency. The letter can recommend starting sugary fluids (4 oz Gatorade, juice, or flat soda + 1 TBSP sugar) and contact the metabolic clinic to determine the next steps. If immediate emergency management is required, call 911 or send the patient to the closest hospital to begin the emergency room protocol. DO NOT provide intralipid.

Feeding progression/starting solids

A child with VLCAD deficiency should start solid foods like any other child when showing signs of readiness. Defer the progression of solid food choices to the metabolic dietitian since the fat from foods will need to be carefully selected and precisely counted. Initial foods include fruits and vegetable purees since these are naturally low in fat.

Screening

For the Condition

Newborn screening by tandem mass spectrometry (MS/MS) identifies children with VLCADD who have elevated C14:1 +/- other long-chain acylcarnitines. The sensitivity of MS/MS is unknown, and the specificity is low. Most infants with elevated C14:1 carnitine are carriers for VLCAD deficiency. If the newborn screen is positive, a metabolic geneticist will usually order additional testing, including quantitative plasma acylcarnitine profile and mutation analysis of the VLCAD gene. In some cases, enzyme assay in fibroblasts, and additional biochemical tests are necessary to confirm the diagnosis.

A normal newborn screening result or plasma acylcarnitine profile does not exclude the diagnosis of VLCADD. An out-of-range screening result does not necessarily mean that the child has VLCADD; however, because the harmful effects of untreated VLCADD can occur soon after birth, follow-up testing must be completed as soon as possible. See the testing section, below, for details.

Of Family Members

Siblings and parents of children identified with VLCADD can be screened by mutation analyses looking for the same mutation. Positive findings may assist genetic counseling, preventive management of illnesses, and avoidance of fasting.

For Complications

After confirmation of diagnosis, initial evaluations for complications should include:
  • Measurement of baseline (serum) creatinine kinase (CK) concentration
  • Measurement of baseline liver transaminases
  • Cardiac echocardiography
  • Electrocardiogram

Presentations

Symptoms of the early form of VLCADD may begin between birth and 4 months of age. Symptoms usually include those associated with cardiomyopathy and multi-organ system involvement. The early form responds poorly to treatment. The "childhood" type may begin in later infancy or early childhood, particularly during fasting or illness. Cardiomyopathy is generally absent but can sometimes be observed. Initial signs/symptoms in the early infancy and childhood types may include:
  • Poor feeding
  • Vomiting
  • Diarrhea
  • Irritability
  • Behavior changes
  • Extreme sleepiness
  • Muscle weakness
  • Lethargy
Since these are non-specific symptoms, one should not exclude other inborn errors of metabolism.
If not treated promptly, patients may experience:
  • Hepatomegaly
  • Difficulty breathing
  • Muscle weakness with exertion
  • Arrhythmia
  • Cardiomyopathy
  • Seizures
  • Brain damage
  • Death
The adult form of VLCADD, which presents with myopathy, may begin in adolescence or adulthood and may be triggered by prolonged exercise, fasting, inadequate calorie intake, and stress. Symptoms may be mild or severe. Adult type symptoms include:
  • Muscle breakdown with exercise or prolonged fasting
  • Muscle aches
  • Weakness
  • Cramps
  • Reddish-brown urine
  • Kidney failure
For those identified after irreversible consequences, global developmental delays and/or abnormalities in the neurological exam may be evident. Sudden death has been reported even in patients with milder forms of the disease. [Coughlin: 2010]

Diagnostic Criteria

Diagnosis is usually based on a positive newborn screening result and subsequent genetic testing or genetic testing in individuals who present with typical symptoms. The ACT sheet recommendations proposed by the American College of Medical Genetics help determine further evaluation for the infant who is screen-positive for VLCAD deficiency (see Confirmatory Algorithm for C14:1 Elevated +/- Other Long-Chain Acylcarnitines (PDF Document 164 KB)).

Additional biochemical testing, guided by a metabolic geneticist, is usually performed to confirm the diagnosis.

The essential features for diagnosis include:
  • Elevation of C14:1 acylcarnitines (may not be present when the child is well)
  • Mutations in the ACADVL gene
  • Biochemical testing in fibroblasts if variations of unknown significance are identified through genetic sequencing

Clinical Classification

VLCADD is clinically heterogeneous, with 3 main phenotypes based on varying degrees of enzyme deficiency.
  • The early onset (infantile) form, associated with a nearly complete absence of the enzyme, is characterized by dilated or hypertrophic cardiomyopathy, arrhythmia, hypotonia, hepatomegaly, hypoglycemia, and high morbidity and mortality usually shortly after birth.
  • The childhood form is milder, with hypoketotic hypoglycemia, similar to medium-chain acyl-CoA dehydrogenase deficiency (MCADD) with increased values of liver function tests and elevated creatine kinase. Symptoms are usually triggered by stress. Cardiomyopathy is rare but can still occur.
  • The mildest form is the adult variant, with exercise or fasting-induced rhabdomyolysis and resembling the muscle form of CPT2 deficiency.

Differential Diagnosis

Early-onset VLCADD may be confused with other rare forms of cardiomyopathy, including glycogen storage disease type 2, Pompe disease, and carnitine disorders, such as carnitine palmitoyl transferase II (CPT II, the neonatal variety only) or carnitine acylcarnitine translocase (CACT) deficiency, LCHAD/TFP deficiency, multiple acyl CoA dehydrogenase deficiency (MADD), and carnitine uptake disorder. VLCADD is distinguished from other disorders through biochemical and molecular testing.

Other differential diagnoses include:
  • Other fatty acid oxidation disorders (medium-chain acyl-CoA dehydrogenase deficiency, long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency/trifunctional protein deficiency, carnitine transporter defect, multiple acyl CoA dehydrogenase, carnitine palmitoyl transferase I, and carnitine-acylcarnitine translocase deficiency). Important clinical features that may help differentiate VLCADD from the other fatty acid oxidation disorders include cardiomyopathy and/or rhabdomyolysis (seen in several but not all of the other disorders) and different metabolites in acylcarnitine and urine organic acid profiles.
  • Ketogenesis defects often present within the first few days of life, although the pattern of presentation in later childhood may be very similar to VLCADD. Vomiting, decreased sensorium, and hepatomegaly are also presenting symptoms. Although hypoketotic hypoglycemia and sometimes hyperammonemia are biochemical features of ketogenesis defects, severe ketoacidosis is the rule. Cardiomyopathy is not seen in defects of ketogenesis.
  • Organic acidurias usually can be differentiated from VLCADD by a urine organic acids and plasma acylcarnitine profile. Urine ketones can be very elevated in organic acidemia and are low or minimally increased in fatty acid oxidation defects.
  • Respiratory chain defects are variable in their presentation. Biochemically, affected individuals have lactic acidosis and ketonemia (often paradoxical – increased ketones after eating). Diagnosis is difficult, and a muscle biopsy is often necessary. Cardiomyopathy can be seen in these conditions, but hypoglycemia is not usually seen except as a result of liver involvement (mitochondrial DNA depletion syndromes).
  • Carbohydrate metabolism defects may present with hypoglycemia, significant lactic acidosis, +/- ketosis, and hepatomegaly. Acylcarnitine profile and urine organic acid profile will help differentiate these disorders from VLCADD (specific abnormalities are seen only in VLCADD and in none of the disorders of carbohydrate metabolism).
The adolescent/adult form may resemble the classic form of carnitine palmitoyl transferase II (CPT II) deficiency, mild forms of multiple acyl CoA dehydrogenase deficiency, McArdle's disease and other rarer muscle glycogen storage disorders, and lipin-1 deficiency. Plasma acylcarnitine profile and genetic tests can differentiate among these possibilities.

Comorbid & Secondary Conditions

There are generally no comorbid conditions as a result of VLCADD. Depending on the severity of the disease and the incidence of metabolic decompensation, the following may occur:
  • Hypertrophic or dilated cardiomyopathy
  • Arrhythmias
  • Respiratory failure
  • Hepatomegaly
  • Fasting and exercise intolerance
  • Muscle cramps and weakness

History & Examination

Current & Past Medical History

The medical history may be completely uninformative. However, recurrent episodes of nausea, vomiting, or listlessness associated with periods of fasting or illness suggest inadequate management. In the adolescent/adult form, there may be a history of muscle cramps and myoglobinuria, particularly with physical stress, prolonged exercise, or fasting/inadequate calorie intake.

Family History

VLCADD is a recessive condition for which consanguinity might be a factor. There may be a history of sudden infant death syndrome (SIDS) in siblings.

Pregnancy/Perinatal History

No pregnancy-related abnormalities are associated with carrying a child with VLCADD.

Developmental & Educational Progress

Developmental milestones and school performance may be affected by severe episodes of decompensation. Progress should be monitored closely and referrals to appropriate services provided as needed.

Schools should be provided with a copy of the emergency metabolic protocol in case of an emergency. See Example of a Letter for Emergency Treatment of VLCADD (Word Document 16 KB).

Schools should be counseled by parents and/or healthcare providers about appropriate meals and snacks, as well as any supplements like medium-chain triglycerides and L-carnitine. The metabolic clinic can provide a letter of medical necessity and prescriptions for the school. See Sample School Letter for Severe VLCADD (University of Utah Metabolic Clinic) (Word Document 21 KB).

Social & Family Functioning

The family's ability to identify and manage episodes of illness and avoid fasting is important to ensure good outcomes.

Physical Exam

General

The physical examination of a well-child with VLCADD is usually normal unless sequelae are present from a previous acute episode. During acute episodes, vomiting, decreased levels of consciousness, and somnolence may be noted.

Vital Signs

Usually normal, unless the child is decompensating.

Growth Parameters

With proper management, children should grow appropriately. It is essential to maintain a healthy body weight in patients with VLCAD deficiency because weight loss can be dangerous. Prevention is key.

Skin

If the patient is deficient in essential fatty acids, the skin may be affected. With proper management, there should be no signs of essential fatty acid deficiency. The metabolic dietitian should ensure that the patient is meeting needs through specific formulas and/or essential fatty acid supplements.

HEENT/Oral

Normal - Since the diet may be high in simple sugars, dental health should be monitored and regular dental cleanings maintained. Fasting precautions should be implemented if the child requires sedation for a dental procedure.

Chest

Normal

Heart

Signs of heart failure may be present in a patient with the infant/early-onset form.

Abdomen

Hepatomegaly may be present during an acute decompensation.

Testing

After a positive newborn screening test, the American College of Medical Genetics recommends measuring a repeat acylcarnitine profile in plasma and obtaining DNA testing. The plasma acylcarnitine profile can be completely normal if the child is well compensated. If abnormal, it can indicate the need to start dietary therapy immediately. With DNA testing, if 2 mutations are identified, parental testing should be considered to determine if the mutations are on 2 different chromosomes (each parent is a carrier of 1 mutation). Diagnosis is confirmed if 2 known pathogenic variants are identified. If only 1 pathogenic variant is identified, functional studies in fibroblasts (acylcarnitine profiling, fatty acid oxidation probe) might be obtained. DNA testing fails to identify about 10% of mutations, and functional studies might be considered if the diagnosis is still uncertain after DNA testing. See Confirmatory Algorithm for C14:1 Elevated +/- Other Long-Chain Acylcarnitines (PDF Document 164 KB).

Laboratory Testing

Baseline testing:
  • Liver function tests
  • Creatine kinase (CK)
When illness occurs:
  • Basic metabolic panel (BMP), including glucose level
  • Ammonia
  • Liver function tests
At tertiary care facilities:
  • Acylcarnitine profile including free/total carnitine
  • Urine organic acids
  • Essential fatty acids, if on a fat-restricted diet with MCT (usually every 6-12 months)
Initial laboratory findings in the early and childhood types may include metabolic acidosis and hypoglycemia.

Genetic Testing

A DNA sequence analysis looking for mutations and deletions/duplications in the ACADVL gene is performed. VLCADD (Genetic Testing Registry) provides a list of labs.

Other Testing

A baseline cardiac echocardiography and EKG should be obtained if clinically indicated.

Analysis of fatty-acid beta-oxidation in cultured fibroblasts or VLCADD enzyme activity in leukocytes, fibroblasts, liver, heart, or skeletal muscle can be used to confirm the diagnosis if it remains in question. This testing is usually ordered by a metabolic geneticist.

Elevated fatty acid levels may be present with hypoglycemia and can help in distinguishing VLCADD and other fatty acid oxidation defects from hyperinsulinemia.

Specialty Collaborations & Other Services

Newborn Screening Services (see NM providers [2])

Many children with VLCADD will be diagnosed by newborn screening. The primary care clinician should collaborate with the newborn screening program to coordinate the initial diagnosis.

Pediatric Metabolics (see NM providers [0])

Refer for collaboration and counseling for parents, as well as ongoing management.

Nutrition, Metabolic (see NM providers [5])

Refer for the formulation of an appropriate low-fat diet and for guidance on the intake of necessary fats, carbohydrates, proteins, vitamins, minerals, and cofactors to support growth and development.

Developmental - Behavioral Pediatrics (see NM providers [2])

Refer if there are any concerns related to sequelae following decompensation or developmental deficits.

Treatment & Management

Pearls & Alerts for Treatment & Management

Avoid factors causing physical stress

Physical stress caused by illness, dehydration, fatigue, and, in some cases, high-fat diets can lead to acute decompensation.

Avoid low-carbohydrate, high-fat, calorie-restricted diets

Avoid these diets. If weight loss is necessary, the metabolic nutritionist should be consulted.

Avoid fasting

Although fasting tolerance improves with age, prolonged fasting in an affected individual can lead to coma and death at any age.

Procedures requiring fasting

Patients with VLCADD are unable to fast before procedures (follow their individualized fasting precautions). Recommend scheduling the first available appointment in the morning. IV glucose should be started (using ER protocol) at the end of the appropriate fasting period and should continue until the individual eats/drinks after the procedure. The metabolic team should communicate this plan with the appropriate individual/team prior to the procedure.

Vaccinations

Vaccinations should be given according to appropriate vaccination protocol. Consider acetaminophen with the first set and ibuprofen (10 mg/kg per dose) from 4 months on. Ibuprofen prevents fever and controls pain allowing the child to eat better.

How should common problems be managed differently in children with VLCADD?

Growth or Weight Gain

In infancy and childhood, slowed growth may be a sign that there is a deficiency (calories or essential fats) or that supplementation with MCT should be increased. If there are concerns about slow growth, work with the metabolic team to monitor growth and adjust the diet. Rapid weight gain should be avoided as weight loss can be dangerous and lead to metabolic decompensation.

Development (Cognitive, Motor, Language, Social-Emotional)

Patients who have experienced metabolic decompensation may have delays in development. Refer to appropriate therapies, such as physical, occupational, speech, or feeding therapy.

Viral Infections

The metabolic clinic should be alerted to any illness that includes a fever or inadequate calorie intake. Treat symptomatically and admit to the hospital if unable to eat or vomiting.

Bacterial Infections

During illness, energy demands are increased and oral intake decreases placing these patients at high risk for metabolic decompensation. Any illness requires management of the underlying etiology and careful monitoring for adequate intake and signs of symptoms of metabolic decompensation. The metabolic clinic should be notified of any illness they can help in direct management and determine when a referral to a tertiary care center is needed. Parents should be encouraged to offer foods and drinks at regular intervals that are high in carbohydrates and low in fat. You may recommend sugary beverages (4 oz juice, Gatorade, or flat soda + 1 TBSP sugar). Pedialyte is too low in calories for these patients.

Common Complaints

Food refusal - In general, children refuse food when sick. Families should have a thermometer at home to check temperature when in doubt. Picky eating or poor eating can be seen in patients with VLCAD deficiency. Usually, it is not a problem as long as the child is growing well. The family should be connected with the metabolic team to provide suggestions and should follow fasting guidelines. If poor eating is a chronic issue, referral to feeding/speech therapy may be necessary.

Other

Patients with VLCADD need early evaluation and treatment for illness. There should be a low threshold for providing interventions, such as IV glucose.

Systems

Endocrine/Metabolism

The overall goal of treatment is to avoid decompensation brought about by physical stressors, such as illness, dehydration, fasting, and in some cases, high-fat foods.

The medical home clinician should ensure that a plan is in place during times of acute illness. The usual treatment is 10% glucose with adequate salts (half or normal saline - depending on age and weight - with 20 mEq/L of potassium chloride) at 1.5-times maintenance, keeping in mind that this treatment does not provide all the needed calories.

Identify and treat the cause for acute decompensation if possible. Oral feedings should be restarted as soon as possible.

Ongoing treatment to prevent complications may include:
  • Fasting avoidance
  • A low-fat diet supplemented with essential fatty acids
  • Medium-chain triglycerides, which do not require the VLCAD enzyme for break-down
  • Cornstarch supplements, sometimes required in children with the childhood form of the disease
  • Low-dose (25 mg/kg per day) carnitine, only used when individuals are carnitine deficient (monitored through laboratory studies)

Specialty Collaborations & Other Services

Nutrition, Metabolic (see NM providers [5])

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

Genetics

Ongoing management, particularly for the child with recurrent decompensations, should involve collaboration with a metabolic geneticist who can offer new research findings and experience, as well as genetic counseling for the family and the patient as he/she nears puberty.

Specialty Collaborations & Other Services

Pediatric Metabolics (see NM providers [0])

Periodic visits are essential to monitor for problems, support families, and provide needed education.

Nutrition/Growth/Bone

Depending on the severity of the enzyme deficiency, children may need restriction of dietary fat and supplementation by medium-chain triglycerides (MCT). This will be determined by the metabolic dietitian who will monitor growth and supplement as necessary. See Commonly Used Medical Foods for VLCADD (University of Utah Metabolic Clinic) (Word Document 60 KB).

Development (general)

In children who have experienced decompensation, developmental delay and/or neurologic symptoms may be present. The medical home clinician should monitor development and educational progress, and if impaired, make referrals as necessary.

Specialty Collaborations & Other Services

Developmental Assessments (see NM providers [236])

May be performed by a child psychologist or, often, with a team-based approach.

Developmental - Behavioral Pediatrics (see NM providers [2])

May be helpful, particularly as part of an evaluation team.

Issues Related to VLCADD

No Related Issues were found for this diagnosis.

Ask the Specialist

How often should an infant with VLCAD deficiency eat?

The appropriate fasting interval is typically weight-based with allowed fasting up to 1 hr per kg body weight (ex: 3.5 kg infant can fast 3.5 hours). The maximum fasting interval for the first year is 8 hours.

Should parents be checking blood sugars using a glucometer?

No, hypoglycemia is a late sign of metabolic decompensation and should not be used. Parents should monitor for signs of decompensation and have a low threshold for contacting their primary care clinician/metabolic team, especially during illness.

Are there any considerations for giving vaccines?

Children with VLCADD should be vaccinated according to a typical vaccination schedule. To avoid fever or poor feeding with vaccines, consider recommending that parents give acetaminophen or ibuprofen.

A child with VLCADD is refusing to eat. What should I do?

Children with VLCADD cannot exceed their maximum fasting interval. If food refusal occurs (without illness), encourage parents to offer a favorite food (within fat goal) or offer a beverage, such as skim milk or a sugary beverage (4 oz juice, Gatorade) + 1 TBSP sugar. Have the family connect with a metabolic dietitian for further suggestions. If food refusal occurs (with illness), recommend sugary beverages and contacting the metabolic clinic to determine next steps. If immediate emergency management required, call 911 or send the patient to the closest hospital to begin the emergency protocol.

Resources for Clinicians

On the Web

VLCADD Nutrition Management Guidelines (Genetics Metabolic Dietitian International)
Guidelines intended for use by metabolic dietitians, physicians, others of the health care team and researchers who collaborate to provide care and advice for individuals with VLCADD.

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

VLCADD (OMIM)
Extensive literature review organized by description, clinical features, genetics, diagnosis, differential diagnosis, management, nomenclature, history, and animal models; Online Mendelian Inheritance in Man.

VLCADD (GeneReviews)
An expert-authored, peer-reviewed, current disease description that applies genetic testing to diagnosis and management information for the condition; U.S. National Library of Medicine.

Helpful Articles

PubMed search for VLCADD in children, last 5 years.

Hesse J, Braun C, Behringer S, Matysiak U, Spiekerkoetter U, Tucci S.
The diagnostic challenge in very-long chain acyl-CoA dehydrogenase deficiency (VLCADD).
J Inherit Metab Dis. 2018;41(6):1169-1178. PubMed abstract

Rovelli V, Manzoni F, Viau K, Pasquali M, Longo N.
Clinical and biochemical outcome of patients with very long-chain acyl-CoA dehydrogenase deficiency.
Mol Genet Metab. 2019;127(1):64-73. PubMed abstract

Spiekerkoetter U, Lindner M, Santer R, Grotzke M, Baumgartner MR, Boehles H, Das A, Haase C, Hennermann JB, Karall D, de Klerk H, Knerr I, Koch HG, Plecko B, Röschinger W, Schwab KO, Scheible D, Wijburg FA, Zschocke J, Mayatepek E, Wendel U.
Treatment recommendations in long-chain fatty acid oxidation defects: consensus from a workshop.
J Inherit Metab Dis. 2009;32(4):498-505. PubMed abstract

Yamada K, Taketani T.
Management and diagnosis of mitochondrial fatty acid oxidation disorders: focus on very-long-chain acyl-CoA dehydrogenase deficiency.
J Hum Genet. 2019;64(2):73-85. PubMed abstract

Clinical Tools

Care Processes & Protocols

ACT Sheet for VLCADD (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 C14:1 Elevated +/- Other Long-Chain Acylcarnitines (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.

VLCADD Acute Illness Protocol (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.

Example of a Letter for Emergency Treatment of VLCADD (Word Document 16 KB)
A sample of a letter for a child with VLCADD who is unable to eat or has high fever/vomiting and needs emergency treatment.

Questionnaires/Diaries/Data Tools

MyFitnessPal
To monitor diet, families can try using MyFitnessPal (free with membership) or another online app that tracks grams of fat.

Other

Sample School Letter for Severe VLCADD (University of Utah Metabolic Clinic) (Word Document 21 KB)
An example of a 1-page letter to a child's school that explains severe VLCADD and the need for modified meals and snacks at schools.

Example of a Travel Letter for VLCADD (Word Document 22 KB)
A sample letter explaining what medications and supplements a person with VLCADD may need to fly with.

Example of Feeding Guidelines for Infant with VLCADD (Word Document 28 KB)
A sample of a modifiable hand out with information about breast and formula feeding the infant with VLCADD.

Patient Education & Instructions

Power Packing and VLCADD (University of Utah Metabolic Clinic) (PDF Document 118 KB)
One-page, printable handout with ideas for calorie-dense snacks for children with fatty oxidation disorders, such as VLCADD.

Baby's First Test: VLCADD (Genetic Alliance)
Information about early signs, follow-up testing, treatment, accessing care, and expected outcomes. Provides links to support services.

Parents' Guide to VLCADD (California Dept. of Health) (PDF Document 203 KB)
A 28-page booklet explaining treatment, inheritance, and testing.

Resources for Patients & Families

Information on the Web

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.

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

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

National & Local 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.

Services for Patients & Families in New Mexico (NM)

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

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.

Authors & Reviewers

Initial publication: January 2011; last update/revision: March 2020
Current Authors and Reviewers:
Author: Chelsea Norman, BS, RDN, CD
Reviewer: Nicola Longo, MD, Ph.D.
Authoring history
2010: first version: Nicola Longo, MD, Ph.D.A
AAuthor; CAContributing Author; SASenior Author; RReviewer

Bibliography

Arnold GL, Van Hove J, Freedenberg D, Strauss A, Longo N, Burton B, Garganta C, Ficicioglu C, Cederbaum S, Harding C, Boles RG, Matern D, Chakraborty P, Feigenbaum A.
A Delphi clinical practice protocol for the management of very long chain acyl-CoA dehydrogenase deficiency.
Mol Genet Metab. 2009;96(3):85-90. PubMed abstract / Full Text

Coughlin CR 2nd, Ficicioglu C.
Genotype-phenotype correlations: sudden death in an infant with very-long-chain acyl-CoA dehydrogenase deficiency.
J Inherit Metab Dis. 2010. PubMed abstract

Hesse J, Braun C, Behringer S, Matysiak U, Spiekerkoetter U, Tucci S.
The diagnostic challenge in very-long chain acyl-CoA dehydrogenase deficiency (VLCADD).
J Inherit Metab Dis. 2018;41(6):1169-1178. PubMed abstract

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

Rovelli V, Manzoni F, Viau K, Pasquali M, Longo N.
Clinical and biochemical outcome of patients with very long-chain acyl-CoA dehydrogenase deficiency.
Mol Genet Metab. 2019;127(1):64-73. PubMed abstract

Spiekerkoetter U, Lindner M, Santer R, Grotzke M, Baumgartner MR, Boehles H, Das A, Haase C, Hennermann JB, Karall D, de Klerk H, Knerr I, Koch HG, Plecko B, Röschinger W, Schwab KO, Scheible D, Wijburg FA, Zschocke J, Mayatepek E, Wendel U.
Treatment recommendations in long-chain fatty acid oxidation defects: consensus from a workshop.
J Inherit Metab Dis. 2009;32(4):498-505. 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.
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