Very long chain Acyl-CoA dehydrogenase deficiency (VLCADD) is an inherited metabolic disease caused by deleterious mutations in the ACADVL gene [1]. In this communication, we describe two novel mutations in a patient with VLCADD and his parents, and suggest a phenotype-genotype correlation.

The full term male infant had uneventful antenatal and perinatal history. His newborn screening was performed at 7 days of age in our facility. Analysis of blood acylcarnitine profile indicated markedly increased levels of long chain acylcarnitines, with significantly elevated C14:1 level of 2.17 µM. Blood samples from the infant and his parents were collected for genetic studies and mutation analysis, after informed consent. Genetic analysis of the infant’s sample showed two heterozygous mutations in the ACADVL gene. Two novel missense mutations ACADVL NW_001270447: c.1768C>T (p.Arg590Trp) and ACADVL NW_001270447: c.1865A>G (p.Glu622Gly) were detected. The father was heterozygous for c.1768C>T (p.Arg590Trp) and the mother was heterozygous for c.1865A>G (p.Glu622Gly). Blood glucose, creatine kinase and alanine aminotransferase levels in the infant were normal, and the baby had no symptom or sign associated with VLCADD. As recommended [1], the parents were instructed to feed the baby boy every 3 h, to avoid fasting, and to seek immediate medical care in case of prolonged febrile disease or decreased food intake.

The boy was asymptomatic until 6 months of age when he presented with poor feeding, vomiting and drowsiness. Investigations revealed hypoglycemia (blood glucose 34 mg/dL), and an elevated serum level of creatine kinase (2126 U/L) and alanine aminotransferase (174 U/L). Blood gases showed metabolic acidosis (pH 7.3, HCO3 15.2 mmol/L, base excess -11 mmol/L). He was treated with intravenous infusions of 10% glucose, sodium bicarbonate, creatine phosphate sodium, caleium dibulyryl cyclic adenosine monophate and mono-ammonium　glycyrrhizinate. He was subsequently fed with medium-chain-triglyceride-enriched formula. After 9 days, he was discharged from the hospital following clinical and laboratory improvement; the levels of creatine kinase (267 U/L) and alanine aminotransferase (42 U/L) returned to normal range. No obvious abnormality was observed at the last follow-up at 9 months of age.

Several studies have addressed the possible genotype-phenotype correlations in VLCADD [2]. According the clinical features of the patient in this report, there was a certain correlation between the genotype and the phenotype. A deeper insight of the correlation may be obtained by functional studies of the novel mutations in the ACADVL gene. The earlier diagnosis is critical to the improvement the prognosis of the patients.

1. Bertrand C,　Largillière C,　Zabot MT,　Mathieu M,　Vianey-Saban C. Very long chain acyl-CoA dehydrogenase deficiency: Identification of a new inborn error of mitochondrial fatty acid oxidation in fibroblasts. Biochim Biophys Acta.　1993;1180:327-9.