ABSTRACT
BACKGROUND: Dilated cardiomyopathy with ataxia syndrome (DCMA) or 3-methylglutaconic aciduria type V is a rare global autosomal recessive mitochondrial syndrome that is clinically and genetically heterogeneous. It is characterized by early-onset dilated cardiomyopathy and increased urinary excretion of 3-methylglutaconic acid. As a result, some patients die due to cardiac failure, while others manifest with growth retardation, microcytic anemia, mild ataxia, and mild muscle weakness. DCMA is caused by variants in the DnaJ heat shock protein family (Hsp40) member C19 gene (DNAJC19), which plays an important role in mitochondrial protein import machinery in the inner mitochondrial membrane. METHODS: We describe a single affected family member who presented with cardiomyopathy, global developmental delay, chest infection, seizures, elevated excretion of 3-methylglutaconic acid, and 3-methylglutaric acid in the urine. RESULTS: Whole-exome sequencing followed by Sanger sequencing revealed a homozygous frameshift variant in the reading frame starting at codon 54 in exon 4 in the DNAJC19 gene (c.159del [Phe54Leufs*5]), which results in a stop codon four positions downstream. Quantitative gene expression analysis revealed that DNAJC19 mRNA expression in this patient was substantially reduced compared to the control. CONCLUSIONS: We present a novel variant in the DNAJC19 gene that causes rare autosomal recessive mitochondrial 3-methylglutaconic aciduria type V. By comparing the current case with previously reported ones, we conclude that the disease is extremely heterogeneous for reasons that are still unknown.
