title: Familial very long chain acyl-CoA dehydrogenase deficiency as a cause of neonatal sudden infant death: improved survival by prompt diagnosis.
abstract: 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.
authors.affiliation: Division of Pediatric Neurology, Department of Pediatrics, Centre Hospitalier de Luxembourg, Luxembourg City, Luxembourg.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Scalais
authors.forename: Jean
authors.initials: J
authors.lastname: Bottu
authors.forename: Ronald J A
authors.initials: RJ
authors.lastname: Wanders
authors.forename: Sacha
authors.initials: S
authors.lastname: Ferdinandusse
authors.forename: Hans R
authors.initials: HR
authors.lastname: Waterham
authors.forename: Linda
authors.initials: L
authors.lastname: De Meirleir
mesh_terms: D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000172:deficiency*; D002331:Carnitine / Q000031:analogs & derivatives / Q000378:metabolism; D002648:Child; D005190:Family; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008052:Lipid Metabolism, Inborn Errors / Q000150:complications*; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D010084:Oxidation-Reduction; D010168:Palmitates / Q000378:metabolism; D066087:Perinatal Death / Q000209:etiology*; D035781:Siblings; D013398:Sudden Infant Death / Q000175:diagnosis*; D016019:Survival Analysis
chemical_list: D010168:Palmitates; C116917:acylcarnitine; D044942:Acyl-CoA Dehydrogenase, Long-Chain; D002331:Carnitine
keywords: fatty acid oxidation defects; rhabdomyolysis; riboflavin; sudden neonatal infant death; very-long chain acyl-CoA dehydrogenase