In neonates,
very long chain acyl-CoA dehydrogenase (
VLCAD) deficiency is often characterized by
cardiomyopathy,
hepatic encephalopathy, or severe hypoketotic
hypoglycemia, or a combination thereof. The purpose of this study was to further elucidate a familial
VLCAD deficiency in three patients, two of whom died in the neonatal period. We report on a family with
VLCAD deficiency. Acyl-
carnitine profiles were obtained from dried blood spot and/or from oxidation of (13) C-
palmitate by cultured skin fibroblasts. In the index patient,
VLCAD deficiency was ascertained by
enzyme activity measurement in fibroblasts and by molecular analysis of
ACADVL. At 30 hr of life, the proband was diagnosed with
hypoglycemia (1.77 mmol/L),
rhabdomyolysis (CK: 12966 IU/L) and hyperlactacidemia (10.6 mmol/L).
Acylcarnitine profile performed at 31 hr of life was consistent with
VLCAD deficiency and confirmed by cultured skin fibroblast
enzyme activity measurement. Molecular analysis of
ACADVL revealed a homozygous splice-site mutation (1077 + 2T>C). The acyl-
carnitine profile obtained from the sibling's original newborn screening cards demonstrated a similar, but less pronounced abnormal profile. In the proband, the initial metabolic crisis was controlled with 10%
dextrose solution and oral
riboflavin followed by specific diet (Basic-F and medium chain
triglyceride (MCT). This clinical report demonstrates a familial history of repeated
neonatal deaths explained by
VLCAD deficiency, and the clinical evolution of the latest affected, surviving sibling. It shows that very early metabolic screening is an effective approach to avoid sudden unexpected death.