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