Long-Chain Acyl CoA Dehydrogenase Deficiency Follow-up

  • Author: Fernando Scaglia, MD, FACMG; Chief Editor: Bruce Buehler, MD   more...
 
Updated: Apr 16, 2012
 

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.
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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.
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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.
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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.
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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.
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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 infancy[5]
  • 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.
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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.
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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.
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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.

Specialty Editor Board

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: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

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

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