Very-long-chain Acyl-CoA Dehydrogenase Deficiency (VLCADD)

Introduction

Very long chain fatty acids (VLCFA) have aliphatic tails of 22 or more carbon atoms, and VLCAD has a chain-length substrate specificity ranging from C12 to C20.

Incidence

VLCADD is estimated to affect 1 in 30,000 to 120,000 newborns.

Genetic inheritance

VLCADD with autosomal recessive inheritance. The defect affects the very long-chain Acyl-CoA dehydrogenase (ACADVL) gene, which has been mapped to chromosome 17p13.1.

Clinical aspects

Three different phenotypes of VLCADD can be distinguished, which mainly depend on the residual VLCAD activity. The severe, early-onset form presents already in the first month of life with a high mortality from cardiac failure (secondary to hypertrophic or dilated cardiomyopathy, pericardial effusion, and/or arrhythmias) and multi-organ failure with hepatomegaly, hypotonia, and intermittent hypoglycemia. The milder, hypoketotic hypoglycemic (or hepatic) form with onset most often in early childhood is associated with low mortality, hypoketotic hypoglycemia, and hepatomegaly, but lacks cardiomyopathy. Finally, the adult form is usually triggered by exercise or fasting and presents with isolated skeletal muscle involvement, intermittent rhabdomyolysis, muscle pain and/or cramps, muscular exercise intolerance, myoglobinuria, and typically normoglycemia. Acute renal failure has been described secondary to rhabdomyolysis. Patients suffering from the more severe forms of VLCADD are typically placed on a diet low in long- and very-long-chain triglycerides, but rich in medium-chain triglycerides and glucose to provide calories. Carnitine supplementation has been controversial. With diet modifications and early-onset thorough care, cardiac dysfunction has been shown to be reversible (occasionally even including extra-corporeal membrane oxygenation as a bridge to recovery).

Precautions before anesthesia

Whenever possible, touch base with a metabolic specialist to discuss the best approach to these patients. Given the high risk of cardiac problems in this population, preoperative workup should include a thorough physical examination, an ECG, and an echocardiography. Blood work to assess kidney and liver function, a (venous) blood gas analysis, serum lactate, electrolytes, urea, creatinine, creatine kinase, and blood glucose.

Anesthetic considerations

Fasting times should be kept as short as possible. Administration of intravenous fluids with high dextrose content (eg, 10% dextrose [in 0.45-0.9% saline or a balanced, lactate-free, isotonic electrolyte solution] at a rate to deliver 8-10 mg/kg/min of glucose) is crucial if vomiting and/or diarrhea prevent oral intake of calories and fluids. Some clinicians even opt to use insulin to help stop catabolism. However, if these patients are otherwise healthy preoperatively (for elective surgery) and can be encouraged to drink reasonable amounts of dextrose-containing (eg, a glucose polymer) clear fluids until 2 hours before induction of anesthesia, then the intravenous dextrose-supplementation can be started once the patient is in the operating room (do not delay the start of anesthesia!). Frequent blood glucose measurements to avoid significant hyper- or hypoglycemia are recommended. While it is important to provide ...