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

Long-Chain Acyl CoA Dehydrogenase Deficiency: Follow-up

Author: Fernando Scaglia, MD, FACMG, Associate Professor of Genetics, Department of Molecular and Human Genetics, Baylor College of Medicine and Texas Children's Hospital
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Updated: Jul 22, 2009

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.

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