eMedicine Specialties > Pediatrics: Genetics and Metabolic Disease > Metabolic Diseases

Long-Chain Acyl CoA Dehydrogenase Deficiency

Fernando Scaglia, MD, FACMG, Associate Professor of Genetics, Department of Molecular and Human Genetics, Baylor College of Medicine and Texas Children's Hospital

Updated: Jul 22, 2009

Introduction

Background

Long-chain 3-hydroxy acyl-coenzyme A dehydrogenase (LCHAD) is 1 of 3 enzymatic activities that make up the trifunctional protein of the inner mitochondrial membrane. The other 2 activities of the protein are 2-enoyl coenzyme A (CoA) hydratase (LCEH) and long-chain 3-ketoacyl CoA thiolase (LCKT). The protein is an octamer composed of 4 alpha subunits that contain the LCEH and long-chain 3-hydroxy acyl-coenzyme A dehydrogenase activities, and 4 beta subunits that contain the LCKT activity. This enzyme complex metabolizes long-chain fatty acids, and the long-chain 3-hydroxy acyl-coenzyme A dehydrogenase activity is specific for compounds of C12-C16 chain length. The genes for the alpha and beta subunits have been localized to chromosome 2.

Affected infants with long-chain 3-hydroxy acyl-coenzyme A dehydrogenase deficiency, which is inherited as an autosomal recessive trait, present in infancy with acute hypoketotic hypoglycemia. These episodes typically appear for the first time after a fast, which usually occurs in the context of intercurrent illness with vomiting.

Pathophysiology

The molecular defect occurs in the mitochondrial trifunctional protein (MTP). Some patients who are deficient in all 3 enzymatic activities of the protein have been described, although most have an isolated long-chain 3-hydroxy acyl-coenzyme A dehydrogenase deficiency, which results in the inability to metabolize long-chain fatty acids. Thus, the clinical features may result from either toxicity due to long-chain acyl-CoA esters that cause cardiomyopathy and cardiac arrhythmias or from a block in long-chain fatty acid oxidation that leads to an inability to synthesize ketone bodies and/or adenosine triphosphate from long-chain fatty acids.

Schematic demonstrating mitochondrial fatty acid beta-oxidation and effects of long-chain acyl CoA dehydrogenase deficiency (LCHAD) deficiency.

Frequency

United States

Occurrence frequency of either isolated long-chain 3-hydroxy acyl-coenzyme A dehydrogenase activity deficiency or trifunctional protein deficiency is unknown in the United States.

International

Analysis of the frequency of the most common mutation (G1528C) revealed a carrier frequency of 1:240 in Finland.

Mortality/Morbidity

In most cases, the disease is severe and may lead to death during the first few months of life. The disease may also be a cause of sudden infant death, even neonatal. For those infants that are diagnosed and treated, a risk for psychomotor retardation is still noted.

Race

Patients from all ethnic groups have been reported.

Sex

No gender predilection is observed because this is an autosomal recessive disorder.

Age

Patients with long-chain 3-hydroxy acyl-coenzyme A dehydrogenase activity deficiency usually present with hypoketotic hypoglycemia, cardiomyopathy, hypotonia, and hepatomegaly at a median age of 6 months. In childhood, the presentation is myopathic. A minority of patients (up to 15%) may present during the neonatal period. A late-onset neuromuscular disease has been reported in MTP deficiency.

Clinical

History

• Acute metabolic crises precipitated by intercurrent infections usually present with hypoketotic hypoglycemia that may be accompanied by cardiomyopathy, hypotonia, and hepatomegaly. These metabolic crises occur more frequently in infancy and early childhood.
• Careful analysis of patients who presented with hypoglycemia revealed that most of them had a constellation of easily missed, nonspecific symptoms before the hypoglycemic episode.
• Many patients may present with myopathy characterized by profound weakness, which may also be accompanied by cardiomyopathy. According to a more recent retrospective study, three fourths of patients studied with trifunctional protein deficiency, including long-chain 3-hydroxy acyl-coenzyme A dehydrogenase activity (LCHAD) deficiency had long term myopathic symptoms.¹
• Some patients may present in infancy or childhood with myoglobinuria or as adults with exercise-induced muscle pains and rhabdomyolysis.
• Some patients present with peripheral sensorimotor polyneuropathy.
• Progressive visual loss has been documented in over 70% of cases with long-chain 3-hydroxy acyl-coenzyme A dehydrogenase activity deficiency.  
• Rarely, affected infants can present with acute cholestatic jaundice or massive total hepatic necrosis in infancy.

Physical

• Neurological examination
  • The acute episode of hypoketotic hypoglycemic encephalopathy may begin with a seizure.
  • Most patients are hypotonic, at least in infancy.
  • Examination may reveal profound weakness, decreased movements, and a frog-leg position.
  • Deep tendon reflexes may be absent in infancy.
  • The patient may toe-walk and display an equinus deformity.
  • Extensor plantar responses have been reported.
• Cardiac: Examination of the heart may reveal cardiomegaly, poor heart sounds, and gallop rhythm.
• Abdomen
  • Most patients have hepatomegaly.
  • Jaundice may develop in infancy along with elevation of the transaminases.
• Ophthalmological examination
  • In the youngest patients, the fundus may be pale. Thereafter, aggregation of pigment has been detected in the posterior pole and macular region.
  • Progressive atrophy of the retinal pigment epithelium, choroid, neural retina, and retinal vessels follow initial pigment abnormalities. This may lead to a completely bare sclera in the central fundus.
  • Posterior staphylomas and delicate lens opacities also may be observed. Cataracts have also been reported.

Causes

• A molecular defect that affects the mitochondrial trifunctional protein (MTP) causes long-chain 3-hydroxy acyl-coenzyme A dehydrogenase activity deficiency.
• Molecular defects are responsible for the 2 types of defect of MTP (ie, long-chain 3-hydroxy acyl-coenzyme A dehydrogenase activity deficiencies, MTP deficiencies).
  • The molecular defect affects the function of the MTP, which contains the activity of long-chain 3-hydroxy acyl-coenzyme A dehydrogenase activity, 2-enoyl-CoA hydratase, and 3-oxoacyl CoA hydratase.
  • In most patients, the deficiency is isolated to long-chain 3-hydroxy acyl-coenzyme A dehydrogenase activity; yet, in some patients, defective activity of all 3 enzymes of the protein is observed.
  • In isolated long-chain 3-hydroxy acyl-coenzyme A dehydrogenase activity deficiency, most of the patients are homozygous for a guanine-to-cytosine transversion at position 1528, involving the alpha subunit of the MTP in the active site domain of the long-chain 3-hydroxy acyl-coenzyme A dehydrogenase activity encoding region. The nicotinamide adenine dinucleotide (NAD) cofactor-binding sequence resides in this region.
  • Other mutations have been described, usually in compound with G1528C.
  • MTP deficiency is caused by several mutations in either alpha or beta subunit DNA encoding regions with resulting decreased functioning of all 3 enzyme activities of long-chain 3-hydroxy acyl-coenzyme A dehydrogenase activity.

Differential Diagnoses

Acidosis, Metabolic
Cardiomyopathy, Dilated
Carnitine Deficiency
Hypoglycemia

Other Problems to Be Considered

Reye syndrome
Other disorders of very long-chain fatty acid oxidation (VLCAD)
Respiratory chain defects (complex I deficiency)

Workup

Laboratory Studies

The following studies may be indicated in long-chain 3-hydroxy acyl-coenzyme A dehydrogenase (LCHAD) deficiency:

• Blood glucose and urine ketones
  • The hallmark biochemical feature of this condition is acute hypoketotic hypoglycemia.
  • Collect urine ketones in the acute episode.
• Creatine phosphokinase, ammonia, uric acid, liver enzymes, lactic acid
  • During acute episodes, elevated levels of creatine phosphokinase are observed.
  • Hyperammonemia may be observed in acute episodes.
  • Elevation of liver transaminases is also observed.
  • A high incidence of lactic acidemia accompanies the metabolic decompensation or acute episode.
• Urine organic acids
  • Test for 3-hydroxylated dicarboxylic acids and nonhydroxylated dicarboxylic acids.
  • Nonhydroxylated dicarboxylic acids are nonspecific changes found in other beta-oxidation defects and in association with liver failure.
• Plasma carnitine levels and acylcarnitine profile
  • Plasma carnitine levels are low.
  • Long-chain acylcarnitine levels are increased with 3-hydroxydicarboxylic derivatives of the C16:0, C18:1, and C18:2 species.
  • The profile may be completely normal during asymptomatic periods.
• Serum fatty acid analyses
  • Serum fatty acid analysis may be diagnostic.
  • Look for 3-hydroxylated compounds even between exacerbations.
• Fatty acid oxidation studies and enzyme assay
  • Diagnosis may be made by study of the oxidation of the 14C-labeled myristic (C14:0) and palmitic (C16:0) acids in fibroblasts.
  • The deficient activity of long-chain 3-hydroxy acyl-coenzyme A dehydrogenase may be diagnosed in fibroblasts, as well as the other enzyme activities of the trifunctional protein.
  • The enzyme usually is measured in fibroblasts in the reverse direction, with 3-oxopalmitoyl CoA as substrate and measurement of the decrease in absorbance at 340 nm of the nicotinamide adenine dinucleotide-reduced form (NADH) electron donor.
• Fasting: In patients in whom the diagnosis has been difficult, an induced fast under strict medical supervision in a facility with expertise in the diagnosis of the inborn errors of metabolism may be considered.
• Molecular studies: Molecular studies (sequencing) to identify the common mutation, G1528C, are available. In addition, if only one mutation is identified in one allele, the presence of deletions can be checked on the other allele by oligonucleotide-based array comparative genomic hybridization (CGH).
• Prenatal diagnosis: Prenatal diagnosis using biochemical studies has been attempted. In appropriate families in whom the molecular defect is known, prenatal diagnosis is also possible by mutation analysis. Guidelines for prenatal screening have been established.²

Imaging Studies

• Chest roentgenography may reveal enlargement of the cardiac silhouette if cardiomyopathy is present.
• Echocardiography may reveal cardiac enlargement, poor contractility with decreased ejection fraction, and pericardial effusion in some cases.

Other Tests

• Abnormal nerve conduction velocities have been recorded in patients with long-chain 3-hydroxy acyl-coenzyme A dehydrogenase deficiency and peripheral neuropathy.
• ECG may reveal left ventricular hypertrophy and cardiac arrhythmias.
• Electroretinography may reveal progression of chorioretinopathy.³
• Mitochondrial enzyme studies may reveal abnormal respiratory chain function in skeletal muscle specimens. A more generalized deficiency of mitochondrial enzymes or a more selective reduction of complex I may be noted.
• If elevated C16-OH ± C18:1-OH and other long chain acylcarnitines are present on newborn screening, the pediatrician should do the following:
  • Contact the family to inform them of newborn screening results and determine clinical status and whether poor feeding, vomiting, and lethargy are present
  • Contact pediatric metabolic specialist
  • Evaluate infant for hepatomegaly, signs of hypoglycemia and metabolic acidosis and cardiomyopathy
  • Evaluate family history to determine whether a history of sudden death in a sibling and whether maternal liver disease was noted during pregnancy
  • Educate family about signs and symptoms of hypoglycemia and metabolic acidosis
• A metabolic specialist needs to confirm or exclude diagnosis of long-chain 3-hydroxy acyl-coenzyme A dehydrogenase deficiency by requesting an acylcarnitine profile and urine organic acid analysis. If carnitine levels are low, consider carnitine supplementation. In addition, an evaluation should be done to exclude hypoglycemia, elevated liver transaminases, bilirubin, lactate, ammonia, and creatine phosphokinase, which could be suggestive of long-chain 3-hydroxy acyl-coenzyme A dehydrogenase and trifunctional protein deficiencies. In addition, sequencing of the gene that encodes long-chain 3-hydroxy acyl-coenzyme A dehydrogenase is clinically available for molecular confirmation. If only one mutation is found in one allele, a possible deletion should be screened in the other allele by using oligonucleotide-based array CGH.

Procedures

• Skin biopsy to obtain cultures of skin fibroblasts for fatty acid oxidation studies or specific enzyme assay is necessary for confirmation of diagnosis.
• Muscle biopsy, although not necessary for diagnosis, may be performed because lactic acidosis present in this condition may suggest a respiratory chain defect.

Histologic Findings

• Pathological evaluation has revealed microvesicular and macrovesicular accumulation of fat in skeletal muscle, heart, and liver. Necrotic myopathy without steatosis has been described, as well as degeneration of muscle fibers. Hepatic cirrhosis has also been observed.
• Ultrastructurally, the mitochondria appear to be increased in size and number with swollen appearance. Condensation of the mitochondrial matrix and irregular cristae is noted.

Treatment

Medical Care

• Evaluation for long-chain 3-hydroxy acyl-coenzyme A dehydrogenase (LCHAD) deficiency may be performed on an outpatient basis with acylcarnitine profile, serum free fatty acids, and urine organic acids; however, patients who are asymptomatic at the time of evaluation may not show abnormalities. If high index of suspicion exists on the basis of the history, a skin biopsy could be performed for fatty acid oxidation studies in fibroblasts. However, the availability of DNA studies (eg, sequencing and oligonucleotide-based array comparative genomic hybridization [CGH]) may supersede the need to start with fatty acid oxidation studies in cultured fibroblasts.
• In cases of acute decompensation with unconfirmed diagnosis, collect samples during the acute episode while the hypoglycemia is corrected.
• If the patient presents with acute hypoketotic hypoglycemic encephalopathy, the main goal is to secure sufficient energy intake by infusions of intravenous glucose.
• The management of affected patients is directed at the avoidance of fasting. Most patients also are provided with uncooked cornstarch and medium-chain triglyceride (MCT) oil supplementation to further decrease exposure to fasting. Oral supplementation with docosahexanoic acid ethyl ester (DHA) may be considered to improve visual function. Consider carnitine supplementation if hypocarnitinemia is present; however, carnitine should not be used during acute decompensation.

Consultations

• Genetic metabolic services
• Nutritionist
• Cardiologist
• Ophthalmologist
• Neurologist

Diet

• A low-fat, high-carbohydrate diet with limited long-chain fatty acid intake (10% of total energy) is beneficial.
• Addition of MCT-oil treatment (providing 10-20% of energy requirements) is reported to be beneficial with improvement in dicarboxylic aciduria and a normalization of the plasma level of long-chain acylcarnitines.
• Coordinating MCT supplementation (0.5 g per kg of lean body mass) with periods of increased activity may improve the metabolic control of children with long-chain 3-hydroxy acyl-coenzyme A dehydrogenase and trifunctional protein deficiency following exercise.   
• The use of uncooked cornstarch (2 g/kg/dose) at bedtime prevents early morning hypoglycemia after the overnight fast.
• Supplementation with vegetable oils, as part of the 10% total long-chain fatty acid intake, provides essential fatty acids (ie, linoleic acid, linolenic acid) and prevents retinal disease, peripheral neuropathy, growth restriction, and dermatitis. Use of flax/walnut oils (containing the least amount of nonessential fatty acids) when compared to canola oil may reduce the accumulation of disease specific acyl-CoA intermediates, preventing peripheral neuropathy.
• Prevention of fasting with frequent feeds is crucial.
• DHA supplementation (100 mg/d) as some reports have demonstrated improvements of visual function with supplementation.
• A daily multivitamin and mineral supplement that includes all fat-soluble vitamins is required.
• Supplementation with heptanoate (C7) triglyceride has been evaluated for other long-chain fatty acid oxidation defects and has been suggested to be potentially useful for long-chain 3-hydroxy acyl-coenzyme A dehydrogenase deficiency; however, this advantage has not been clearly documented.
• Because the incidence of obesity and overweight is increasing among children with long-chain 3-hydroxy acyl-coenzyme A dehydrogenase or trifunctional protein deficiency, a diet higher in protein and lower in carbohydrates may help to lower total energy intake and maintaining good metabolic control. However, long-term studies are needed in order to determine whether higher protein diets reduce risks of overweight and obesity.

Activity

• Advise tempered activity when increased risk for rhabdomyolysis and myoglobinuria exists.
• Advise avoidance of strenuous exercise activity and maintenance of adequate fluid intake to prevent dehydration with physical activity.
• Advise restriction of activity when cardiomyopathy is present.

Medication

Try carnitine supplementation in patients with evident hypocarnitinemia and continue if symptoms improve; however, start carnitine supplementation with caution during acute fulminant symptoms because of the potential risk of cardiac arrhythmias.

Dietary supplements

L-carnitine at high doses corrects the metabolic abnormalities and hypocarnitinemia present in cases of long-chain 3-hydroxy acyl-coenzyme A dehydrogenase (LCHAD) deficiency. It may be important for the conjugation and excretion of fatty acids, for the enhancement of the excretion of toxic metabolites, and to generate free CoA; however, use with extreme caution during acute metabolic crises.

Levocarnitine (Carnitor)

An amino acid derivative synthesized from methionine and lysine, required in energy metabolism. Can promote excretion of excess fatty acids in patients with defects in fatty acid metabolism or specific organic acidopathies, which bioaccumulate acyl CoA esters. Normal levels occur in liver, and mild level increases occur in skeletal muscle.
High doses are able to restore the level of free carnitine in plasma to normal, and many patients improve with this therapy; however, the concentration of long-chain acyl-carnitines increases, which can be detrimental and cause serious cardiac arrhythmias in fulminant crises.
Use in long-chain fatty acid oxidation disorders (eg, LCHAD deficiency, MTP deficiency) is a matter of continued debate, mainly during acute fulminant crises when it enhances the formation of long-chain acylcarnitines, which may cause ventricular arrhythmogenesis.

Dosing

Adult

1 g/dose PO/IV tid; not to exceed 3 g/d

Pediatric

100-200 mg/kg/d PO divided bid/tid; not to exceed 3 g/d

Interactions

None known

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Do not use in acute metabolic crises; monitor blood chemistries, vital signs, plasma carnitine concentrations and overall clinical condition; in secondary carnitine deficiency, numerous metabolic disorders must be diagnosed correctly before initiation of carnitine supplementation; use in long-chain fatty acid oxidation defects (eg, LCHAD deficiency, trifunctional protein deficiency, VLCAD deficiency) may enhance formation of long-chain acylcarnitines, which may cause ventricular arrhythmogenesis; adverse effects with toxic doses are nausea, vomiting, diarrhea, and a fish odor derived from a metabolite of carnitine (trimethylamine)

Follow-up

Further Inpatient Care

• Admit patients with long-chain 3-hydroxy acyl-coenzyme A dehydrogenase (LCHAD) deficiency for medical management of acute hypoketotic hypoglycemic encephalopathy.
  • Dextrose (10%) at rates of 10 mg/kg/min or greater may be required to achieve normoglycemia. Do not estimate rate of intravenous (IV) glucose infusion on blood glucose levels alone.
  • In principle, use IV carnitine only in cases of documented severe secondary carnitine deficiency. Carnitine therapy in long-chain fatty acid oxidation disorders is in question because it promotes long-chain acylcarnitine formation, and these acylcarnitines may cause ventricular arrhythmogenesis.
  • Carefully monitor liver transaminases because acute hepatic dysfunction may accompany the metabolic crises.
• Admit patient for management of rapidly evolving cardiomyopathy that may or may not be associated with the hypoglycemic crises.
• Admit patient for management of severe rhabdomyolysis and myoglobinuria to prevent renal failure.

Further Outpatient Care

• Aggressively treat infections and fever to prevent a catabolic state.
• Carefully review diet compliance regarding avoidance of fasting, compliance with fat-restricted diet, supplementation of uncooked cornstarch, and intake of medium-chain triglyceride (MCT) oil.
• Monitor carnitine levels and determine if carnitine supplementation is required.
• Refer patient for ophthalmological evaluation for possible pigmentary retinopathy. All of these subjects should have a baseline ophthalmological evaluation within the first month of diagnosis and annual follow-ups. Fundus photography and repeated electroretinography examinations should be performed.
• Conduct a neurological evaluation with nerve conduction studies to assess for possible peripheral neuropathy.

Inpatient & Outpatient Medications

• Medications include L-carnitine, which should be tried in patients with evident hypocarnitinemia and should be continued if it ameliorates the symptoms. Use with caution during acute episodes because L-carnitine could potentially trigger cardiac arrhythmias.

Transfer

• If diagnosis of long-chain 3-hydroxy acyl-coenzyme A dehydrogenase deficiency is suspected but workup facilities are inadequate and no metabolic specialists are available, transfer of patient to a tertiary care hospital for further workup and management may be necessary.

Deterrence/Prevention

• Prevent fasting with frequent feeds and use of uncooked cornstarch to avoid episodes of hypoglycemia.
• Aggressively treat infections and fever to prevent a catabolic state.
• Advise a fat-restricted diet with high-carbohydrate content. Triacylglycerols should provide less than 10-15% of the patient's total energy supply. Supplementation of dietary fat with medium-chain fatty acids is necessary.
• Use docosahexanoic acid to prevent retinal degeneration.
• Ensure carnitine supplementation in patients with documented secondary carnitine deficiency, especially if it contributes to alleviation of symptoms.
• Advise avoidance of exercise and dehydration with hot temperatures because rhabdomyolysis and myoglobinuria may occur with long-chain 3-hydroxy acyl-coenzyme A dehydrogenase deficiency.
• Screening for long-chain 3-hydroxy acyl-coenzyme A dehydrogenase deficiency should be performed in newborns from mothers with hepatic complications during pregnancy such as acute fatty liver of pregnancy or severe hemolytic anemia, elevated liver enzymes, low platelet count (HELLP) syndrome.

Complications

• Psychomotor retardation and seizures derived from episodes of hypoketotic hypoglycemic encephalopathy
• Hypotonia and delayed motor development that may be permanent or transient after symptomatic periods
• Hepatic dysfunction that may be as severe as massive total hepatic necrosis in infancy
• Dilated cardiomyopathy that may present as a rapidly fatal cardiomyopathy in infancy⁴
• Peripheral neuropathy
• Pigmentary retinopathy
• Pregnancy: Pregnancy complications reported in long-chain 3-hydroxy acyl-coenzyme A dehydrogenase deficiency carriers (with a long-chain 3-hydroxy acyl-coenzyme A dehydrogenase deficient fetus), include HELLP syndrome and acute fatty liver of pregnancy.

Prognosis

• In long-chain 3-hydroxy acyl-coenzyme A dehydrogenase deficiency, the fulminant acute symptoms may be difficult to manage and resistant to therapeutic attempts (with high mortality) because the presentations may involve a lethal acute liver failure, a rapidly evolving cardiomyopathy, or hypoketotic hypoglycemic encephalopathy. However, treatment may improve the long-term prognosis.
• Conventional therapy may not be sufficient to prevent ophthalmological changes; however, early diagnosis and adequate therapy may delay the progression of retinal complications.

Patient Education

• Advise family members to learn cardiopulmonary resuscitation (CPR).
• Teach family members to recognize signs and symptoms of hypoglycemia and instruct them to provide oral sources of glucose, glucose gel, or glucagon injection while waiting for emergency aid.
• Educate family members about frequent feeds and avoidance of fasting in general. If decreased oral intake occurs, the child should be seen immediately at the pediatrician's office or rushed to the emergency department.
• Educate the family about the importance of a fat-restricted high-carbohydrate diet with MCT oil supplementation and use of uncooked cornstarch to prevent episodes of hypoglycemia (see Diet).
• Provide education about routine ophthalmological follow-up care to screen for the onset of pigmentary retinopathy.
• Educate the family about pregnancy complications mainly described in heterozygous mothers giving birth to affected fetuses (eg, HELLP syndrome, acute fatty liver of pregnancy).
• Arrange for genetic counseling and discussion of recurrence risk for future pregnancies.
• Educate about the possibility of prenatal diagnosis, which may be performed by measuring acylcarnitine profiles, measuring the activity of specific enzymes, or by searching for identified mutations (G1528C) from amniocytes or chorionic villus cells.
• Provide education about carnitine supplementation if significant hypocarnitinemia during the asymptomatic state is documented.

Miscellaneous

Medicolegal Pitfalls

• Failure to investigate long-chain 3-hydroxy acyl-coenzyme A dehydrogenase (LCHAD) deficiency as a cause of dilated cardiomyopathy may cause delays in treatment and unnecessary evaluation for cardiac transplantation.
• Failure to recognize long-chain 3-hydroxy acyl-coenzyme A dehydrogenase deficiency and to obtain adequate samples during a critical episode of hypoketotic hypoglycemic encephalopathy may put the patient at further risk of CNS dysfunction or death.
• Failure to inform the family about special diet requirements (eg, low fat, high carbohydrates) might place the patient at risk for another episode of hypoketotic hypoglycemia.
• Failure to evaluate for other complications, such as pigmentary retinopathy and progressive sensorimotor neuropathy, is a potential medical/legal pitfall.
• Failure to recognize hemolytic anemia, elevated liver enzymes, low platelet count (HELLP) syndrome or acute fatty liver of pregnancy as possible complications from long-chain 3-hydroxy acyl-coenzyme A dehydrogenase deficiency in carrier females is a potential pitfall.
• Failure to screen for long-chain 3-hydroxy acyl-coenzyme A dehydrogenase deficiency in the newborn from mothers with hepatic complications during pregnancy such as acute fatty liver of pregnancy or severe HELLP syndrome is a potential medical/legal pitfall.
• Failure to follow-up on abnormal newborn screening results with elevated C16-OH ± C18:1-OH suggestive of long-chain 3-hydroxy acyl-coenzyme A dehydrogenase deficiency.

Special Concerns

• AFLP and HELLP syndrome are serious conditions that may occur during pregnancy in heterozygous women whose fetuses later are found to have an LCHAD deficiency. In either of these cases, rule out LCHAD deficiency in the fetus or in the newborn baby.

Multimedia

Media file 1: Schematic demonstrating mitochondrial fatty acid beta-oxidation and effects of long-chain acyl CoA dehydrogenase deficiency (LCHAD) deficiency.

References

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Keywords

long-chain acyl CoA dehydrogenase deficiency, LCHAD deficiency, trifunctional protein deficiency, hypoketotic hypoglycemia, vomiting, hypotonia, cardiomyopathy, sudden infant death, hepatic necrosis, cholestatic jaundice, hepatomegaly, cardiomegaly, cataracts, treatment, diagnosis

Contributor Information and Disclosures

Author

Fernando Scaglia, MD, FACMG, Associate Professor of Genetics, Department of Molecular and Human Genetics, Baylor College of Medicine and Texas Children's Hospital
Fernando Scaglia, MD, FACMG is a member of the following medical societies: American College of Medical Genetics, American Society of Human Genetics, Society for Inherited Metabolic Disorders, and Society for the Study of Inborn Errors of Metabolism
Disclosure: Nothing to disclose.

Medical Editor

Karl S Roth, MD, Professor and Chair, Department of Pediatrics, Creighton University School of Medicine
Karl S Roth, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American College of Nutrition, American Pediatric Society, American Society for Clinical Nutrition, American Society of Nephrology, Association of American Medical Colleges, Medical Society of Virginia, New York Academy of Sciences, Sigma Xi, Society for Pediatric Research, and Southern Society for Pediatric Research
Disclosure: MDS Pharma Salary Employment

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Margaret M McGovern, MD, PhD, Professor and Chair of Pediatrics, Stony Brook University, New York
Margaret M McGovern, MD, PhD is a member of the following medical societies: American Academy of Pediatrics and American Society of Human Genetics
Disclosure: Genzyme Grant/research funds PI

CME Editor

Paul D Petry, DO, FACOP, FAAP, Consulting Staff, Freeman Pediatric Care, Freeman Health System
Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association
Disclosure: Nothing to disclose.

Chief Editor

Bruce Buehler, MD, Professor, Department of Pediatrics, Pathology and Microbiology, Executive Director, Hattie B Munroe Center for Human Genetics, University of Nebraska Medical Center
Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association
Disclosure: Nothing to disclose.

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