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

J Med Case Rep. 2021 Sep 1;15(1):441. doi: 10.1186/s13256-021-03013-y.

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.

Keywords: ACADVL; Convulsions; High anion gap metabolic acidosis; Hypoketonemic hypoglycemia; Very long-chain acyl-CoA dehydrogenase deficiency.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Acyl-CoA Dehydrogenase, Long-Chain / genetics
  • Child
  • Coenzymes
  • Congenital Bone Marrow Failure Syndromes
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Lipid Metabolism, Inborn Errors* / genetics
  • Mitochondrial Diseases
  • Muscular Diseases
  • Mutation
  • Pregnancy

Substances

  • Coenzymes
  • Acyl-CoA Dehydrogenase, Long-Chain

Supplementary concepts

  • VLCAD deficiency