Very-long-chain Acyl-CoA dehydrogenase (VLCAD) deficiency is characterized by 2 phenotypes: hypoketotic hypoglycemia without cardiac involvement or hypoketotic hypoglycemia in the neonatal period with onset of lethal hypertrophic cardiomyopathy with pericardial effusion at 3-5 months. In both phenotypes, the membrane bound VLCAD is deficient. We describe 3 families in which VLCAD deficiency was documented. The first was detected by blood spot acylcarnitine analysis at birth promoted by a previous SIDS sibling. Enzyme analysis of fibroblasts confirmed the diagnosis. At 2½ years, he has only had hypoglycemia. The second family lost a previous child with sudden onset of cardio-respiratory failure. Prenatal diagnosis of the next pregnancy was accomplished by in vitro probe of the pathway in amniocytes and confirmed by direct enzyme assay. Diagnosis was reconfirmed by acylcarnitine analysis and fibroblast enzyme assays at birth. At 10 months, he has suffered only hypoglycemia while cardiac status remains normal. The third family had no prior history and the child presented at 3 months with cardiomegaly, hepatomegaly, hypoglycemia and respiratory arrest. VLCAD deficiency was verified by both acylcarnitine analysis and fibroblast enzyme analysis. All three affected children have responded well to Portagen formula (high MCT content) and L-Carnitine supplement, with reversal of the acute life threatening illness in the last patient.

VLCAD deficiency should be identified when hypoglycemia, with or without hypertrophic cardiomyopathy, presents during the neonatal period or between 3-5 months. Rapid (18 hrs) diagnosis can be achieved neonatally, subsequently, or even post-mortem by acylcarnitine analysis of whole blood on Guthrie cards. Prenatal diagnosis in families known to be affected can also be achieved, allowing early intervention.