Clinical phenotype and gene mutation of short-chain acyl-coenzyme A dehydrogenase deficiency in a Chinese family

Abstract

Objective To analyze the clinical phenotype and genetic characteristics of short-chain acyl-coenzyme A dehydrogenase deficiency (SCADD). Methods and Results The proband was one month and 14 days old girl, who presented mental and motor retardation, hypotonia and epileptic seizures (convulsive seizures and generalized tonic seizures). Physical examination showed café-au-lait-spot on her left face and left upper abdomen. Ethylmalonic acid and methylsuccinic acid in urine and butyryl carnitine in whole blood were elevated. Inter-ictal discharges in video electroencephalogram (VEEG) showed burst- suppression wave. Cranial MRI demonstrated multiple cortical malformations in the left cerebral hemisphere and right frontal lobe. Genetic test showed the patient had c.795 + 1G > A homozygous mutation of ACADS gene inherited from asymptomatic parents who carried heterozygous mutations in the same locus. The patient was clearly diagnosed as SCADD, and her family was diagnosed as SCADD pedigree. The patient was treated by prednisone [4 mg/(kg·d)] and levetiracetam [30 mg/(kg·d)], and then oral vitamin B2 [10 mg/(kg·d)] was added. No seizures recurred as yet. Conclusions Clinical manifestations of SCADD include mental and motor retardation, hypotonia, early-onset epileptic encephalopathy, elevated ethylmalonic acid, methylsuccinic acid in urine and butyryl carnitine in whole blood, and it might result in cortical malformations. The homozygous mutation c.795 + 1G > A of ACADS gene was pathogenetic, and was reported for the first time.

Keywords

• Amino acid metabolism, inborn errors
• Phenotype
• Genes
• Mutation
• Pedigree