JIMD Reports, Volume 39

Irene C. Huffnagel, Egbert J. W. Redeker, Liesbeth Reneman, Frédéric M. Vaz, Sacha Ferdinandusse, Bwee Tien Poll-The, Huffnagel, Irene C., Redeker, Egbert J. W., Reneman, Liesbeth, Vaz, Frédéric M., Ferdinandusse, Sacha, Poll-The, Bwee Tien

We report the major diagnostic challenge in a female patient with signs and symptoms suggestive of an early-onset mitochondrial encephalopathy. Motor and cognitive development was severely delayed and brain MRI showed signal abnormalities in the putamen and caudate nuclei. Metabolic abnormalities included 3-methylglutaconic aciduria and elevated lactate levels in plasma and cerebrospinal fluid, but were transient. Whole exome sequencing at the age of 25 years finally revealed compound heterozygous mutations c.[229G>C];[563C>T], p.[Glu77Gln];[Ala188Val] in the ECHS1 gene. Activity of short-chain enoyl-CoA hydratase, a mitochondrial enzyme encoded by the ECHS1 gene, was markedly decreased in lymphocytes. Retrospective urine analysis confirms that elevated levels of S-(2-carboxypropyl)cysteamine, S-(2-carboxypropyl)cysteine, and N-acetyl-S-(2-carboxypropyl)cysteine can be a diagnostic clue in the disease spectrum of ECHS1 mutations.