Carnitine Deficiency Follow-up

Admit patients with carnitine deficiency for medical management of acute metabolic decompensation.

Prescribe 10% dextrose in water at rates of 10 mg/kg/min or higher to achieve normal glucose concentrations. If the rate of glucose infusion is based on blood glucose level alone, it may underestimate carbohydrate demand because tissues are depleted of glycogen stores.

Provide intravenous (IV) carnitine if the patient is known to have carnitine deficiency and a defect affecting the oxidation of long chain fatty acids has been excluded.

Carefully monitor adequate carnitine dose in primary and secondary carnitine deficiencies by evaluating plasma carnitine levels during follow-up visits. Carefully review diet compliance in secondary carnitine deficiency, considering avoidance of fasting, intake of fat-restricted, high-carbohydrate diet, and other dietary supplements that may be needed, such as riboflavin or glycine. Treat infections aggressively.

Medications include carnitine for primary and secondary carnitine deficiency, as well as other cofactors that may be needed for different conditions associated with secondary carnitine deficiency (eg, riboflavin, coenzyme Q, biotin, hydroxocobalamin, betaine, glycine). If a seizure disorder has developed secondary to a past episode of hypoglycemia, valproic acid should not be used as an anticonvulsant.

Patients may require transfer to a tertiary care center in which a more specialized metabolic workup for further diagnostic evaluation can be performed.

The following are indicated in patients with carnitine deficiency:

• Prevent fasting with frequent feedings to avoid triggering episodes of hypoglycemia.
• Treat infections aggressively to prevent a catabolic state.
• Snacks and liquids should be consumed before exercise.
• Avoid exercise and dehydration with warm temperatures because attacks of rhabdomyolysis may occur with certain conditions that cause secondary carnitine deficiency.
• For fatty acid oxidation disorders, follow a fat-restricted diet with high carbohydrate content.
• Ensure uninterrupted carnitine supplementation.

The following complications may occur:

• Dilated cardiomyopathy with congestive heart failure and pericardial effusion
• Sudden infant death syndrome (SIDS)
• Rhabdomyolysis with myoglobinuria and secondary renal failure
• Hypotonia
• Hypochromic microcytic anemia
• Failure to thrive
• GI dysmotility
• Pigmentary retinopathy
• Peripheral neuropathy
• CNS dysfunction with developmental delay, pyramidal signs, and athetoid movements

The prognosis of patients with carnitine deficiency is as follows:

• Primary carnitine deficiency

  • Patients with primary carnitine deficiency have excellent prognosis with oral carnitine supplementation.
  • If the disorder is unrecognized, mortality may occur from cardiac failure, arrhythmias, or sudden death.
  • Lifelong treatment with L-carnitine and avoidance of fasting are required. Hypoglycemia or sudden deaths from arrhythmias (even without cardiomyopathy) have been reported in patients who stop their carnitine supplementation against medical advice.
• Secondary carnitine deficiency

  • Prognosis of secondary carnitine deficiency depends on the nature of the disorder.
  • Translocase deficiency and the infantile form of carnitine palmitoyltransferase II (CPT-II) deficiency have very poor prognosis regardless of treatment.^[9]
  • In general, disorders of fatty acid oxidation require lifelong prevention of fasting and diet modification.
  • Other metabolic disorders that cause secondary carnitine deficiency, such as organic acidemias, require lifelong diet modification and nutritional supplements.

Patient education should involve the following:

• Family members should receive education once the work-up initiated after newborn screening results suggests primary carnitine deficiency in the newborn or in the mother.
• Family members should receive cardiopulmonary resuscitation (CPR) training (cases of apnea or near-miss SIDS).
• Family members should be taught to recognize early signs and symptoms of hypoglycemia and should be instructed to provide either glucose gel or glucagon injection while waiting for emergency aid.
• Educate family members about frequent feedings and avoidance of fasting in general. If oral intake is decreased or poor, the child should be seen immediately at pediatrician's office or rushed to the emergency room.
• Educate family members about the importance of continuing carnitine supplementation.
• Educate family members about adhering to fat-restricted diet in fatty acid oxidation disorders or special protein-restricted diet in organic acidemias causing secondary carnitine deficiency.
• Refer parents for genetic counseling and discussion of recurrence risk for future pregnancies.
• Educate family members about the possibility of prenatal diagnosis. If the molecular defect has been established in the proband (primary carnitine deficiency or medium-chain acyl-CoA dehydrogenase [MCAD] deficiency), molecular analysis can be performed.