A novel mutation in ACADVL causing very long-chain acyl-coenzyme-A dehydrogenase deficiency in a South Asian pediatric patient: a case report and review of the literature

Abstract

Background Very long-chain acyl-coenzyme-A dehydrogenase deficiency is a rare, severe life-threatening metabolic disorder of mitochondrial fatty acid oxidation, caused by mutations in ACADVL gene. Here we present a genetically confirmed case of a South Asian baby girl with severe, early-onset form of very long-chain acyl-coenzyme-A dehydrogenase deficiency due to a novel mutation in ACADVL gene. Case presentation Index case was the second baby girl of second-degree consanguineous South Asian parents. She had an uncomplicated antenatal period and was born by spontaneous vaginal delivery at term with a birth weight of 2910 g. She had been noted to have fair skin complexion, hypotonia, and 3 cm firm hepatomegaly. Since birth, the baby developed grunting, poor feeding, and recurrent episodes of symptomatic hypoglycemia and convulsions with multiple semiology. Her septic screening and urine ketone bodies were negative. The baby had high anion gap metabolic acidosis and elevated transaminases and serum creatine phosphokinase levels. Echocardiogram at 4 months revealed bilateral ventricular hypertrophy. Acylcarnitine profile revealed elevated concentrations of tetradecanoylcarnitine (C14), tetradecanoylcarnitine C14:1, and C14:1/C16. Unfortunately, the baby died due to intercurrent respiratory illness at 4 months of age. Sequence analysis of ACADVL gene in perimortem blood sample revealed homozygous frame shift novel variant NM_001270447.1, c.711_712del p.(Phe237Leufs*38), which confirmed the diagnosis of very long-chain acyl-coenzyme-A dehydrogenase deficiency. Conclusions This case demonstrates the importance of early diagnosis and management of very long-chain acyl-coenzyme-A dehydrogenase deficiency in improving the outcome of the patients. Implementation of newborn screening using tandem mass spectrometry in Sri Lanka will be beneficial to reduce the morbidity and mortality of treatable disorders of inborn errors.

Alfalfa Xeno-miR168b Target CPT1A to Regulate Milk Fat Synthesis in Bovine Mammary Epithelial Cells

“…ACADL plays an important role in the β oxidation of long-chain fatty acids, and its deficiency or deletion will cause mitochondrial dysfunction and then affect lipid metabolism [ 41 ]. ACADVL and ACADM genes can participate in biological processes related to lipid metabolism, affect the synthesis and decomposition of fatty acids and glycerol, and play a vital role in lipid metabolism [ 42 , 43 , 44 ]. The low expression of CPT1A affects the fatty acid metabolism of BMECs and inhibits the synthesis and accumulation of cellular lipids, which is also consistent with the result that the overexpression of xeno-miR168b inhibits fatty acid production.…”

Postmortem diagnosis of very long chain acyl‐CoA dehydrogenase (VLCAD) deficiency in a neonate with sudden cardiac death

“…Due to an acute clinical presentation prior to availability of screening results, or lack of newborn screening in some reported cases, it may not be possible to implement intervention. 17 , 18 , 19 However, intervention with dextrose containing intravenous fluids and MCTs may alter the prognosis if initiated early enough postnatally. 16 Scalais et al reported a family in which the first two children died of sudden unexplained cardiopulmonary arrest at less than 36 hours of age.…”