Novel magnetic resonance imaging findings in a patient with short chain acyl CoA dehydrogenase deficiency

Abstract

Reports on magnetic resonance imaging findings in patients with short chain acyl -Coenzyme A dehydrogenase (SCAD) deficiency, an autosomal recessive disorder caused by mutations in the acyl-Coenzyme A dehydrogenase (ACADS), are limited. Many asymptomatic carriers of ACAD variants have also been described necessitating careful evaluation of clinical and biochemical findings for an accurate diagnosis. Here we report a an infant with short chain acyl -Coenzyme A dehydrogenase (SCAD) deficiency diagnosed based on the characteristic biochemical findings and confirmed by genetic testing. He presented with refractory seizures and neuro regression at 4 months of age. His metabolic work up revealed elevated butyryl carnitine in plasma and ethyl malonic acid in urine. Magnetic resonance imaging of the brain showed cortical and basal ganglia signal changes with cortical swelling. Serial scans showed progression of the lesions resulting in cystic leukomalacia with brain atrophy. Exome sequencing revealed a novel homozygous nonsense variation, c.1146C > G (p.Y382Ter) in exon ten of ACADS which was further validated by Sanger sequencing. Both parents were heterozygous carriers. Follow up at 15 months showed gross psychomotor retardation and refractory seizures despite being on optimal doses of anti-epileptic medications, carnitine and multivitamin supplementation. This report expands the phenotypic and genotypic spectrum of SCAD deficiency.

Broadening the Picture of Short-Chain Acyl-CoA Dehydrogenase Deficiency: A Case Report with Microcephaly, Leukoencephalopathy, and Characteristic Magnetic Resonance Spectroscopic Findings

“…11 Chiplunkar et al have also recently reported an infant with hyperintensities in the white matter and basal ganglia that quickly progressed to cystic leukomalacia and atrophy. 12 Our patient's brain MRI findings indicate disturbed myelination with signs of multifocal leukoencephalopathy, which has not been reported so far at the course of the disease. Asymptomatic patients with SCADD have a very good outcome even when deleterious mutations are present.…”

Quantification of Differential Metabolites in Dried Blood Spots Using Second-Tier Testing for SCADD/IBDD Disorders Based on Large-Scale Newborn Screening in a Chinese Population

“…Previous reports of SCADD have described affected patients with multiple signs, including hypoglycemia, developmental delay, lactic acidosis, hypotonia, seizures, and cardiomyopathy, who exhibit variable responses to treatment and different outcomes (30)(31)(32). Of particular note, the most frequent autosomal recessive variant of the ACADS gene in our center was c.1031A>G (p. E344G) in exon 9.…”

Data_Sheet_1.docx

“…Previous reports of SCADD have described affected patients with multiple signs, including hypoglycemia, developmental delay, lactic acidosis, hypotonia, seizures, and cardiomyopathy, who exhibit variable responses to treatment and different outcomes (30)(31)(32). Of particular note, the most frequent autosomal recessive variant of the ACADS gene in our center was c.1031A>G (p. E344G) in exon 9.…”