Long-chain Acyl-CoA Dehydrogenase Deficiency (LCADD)

Introduction

Long-chain fatty acids (LCFA) are fatty acids with aliphatic tails of 13 to 21 carbon atoms and LCAD has a chain-length substrate specificity ranging from C12 to C20.

Incidence

Unknown, but the carrier frequency in Finland has been estimated to be 1 in 240.

Genetic inheritance

Autosomal recessive. The defect affects the long-chain Acyl-CoA dehydrogenase (ACADL) gene, which has been mapped to chromosome 2q34. Only limited information is available for this disorder.

Diagnosis

Previous episodes of lethargy, hypoglycemia, and/or metabolic acidosis prior to the diagnosis are common and are often triggered by minor (viral) infections or fasting.

Clinical aspects

Untreated, episodes of lethargy, hypoglycemia, and/or metabolic acidosis are common and often triggered by minor (viral) infections or fasting. Other presenting symptoms may include seizures, coma, cardiomegaly, muscular hypotonia and weakness, vomiting, respiratory arrest, and jaundice. Compared to MCADD patients, LCADD patients usually present at an earlier age (first 6 months of life) with episodes of hypoglycemia, coma, and more profound cardiorespiratory depression. Developmental delay seems a common finding in LCADD patients. The hypoglycemic episodes are usually not associated with accumulation of ketone bodies (hypoketotic hypoglycemia). LACD is also involved in surfactant production in alveolar Type II pneumocytes and LCADD seems to result in reduced pulmonary compliance and increased permeability of the alveolar epithelium. In fact, two infants with sudden death were found to be LACD-deficient in their lungs. However, its clinical significance for LCADD patients in general remains to be determined.

Precautions before anesthesia

Whenever possible, touch base with a metabolic specialist to discuss the best approach to these patients.

Anesthetic considerations

There are no reports with regards to anesthesia in these patients. However, in general the same anesthetic considerations that have been described for VLCADD should also apply to these patients. Abnormal surfactant with respiratory symptoms may indicate the need for a preoperative chest radiograph and make perioperative atelectasis prevention crucial, which may require postoperative invasive or noninvasive ventilation (eg, CPAP/BiPAP) and/or physiotherapy. In patients with a history of seizures, epileptogenic drugs (eg, meperidine/pethidine) should be avoided. Anticonvulsant therapy should be continued until the morning of surgery and resumed as soon as possible postoperatively and given intravenously if oral intake is not possible. Chronic anti-seizure treatment may interfere with the metabolism and elimination of other drugs that share the same metabolic pathways.