Infantile Manifestation of a Mitochondriopathy due to a Homozygous Mutation in DARS2 Gene

Case Study: The DARS2 gene encodes the mitochondrial aspartyl-tRNA synthetase 2. Mutations lead to leukoencephalopathy with brain stem and spinal cord involvement with elevated lactate peak in MR spectroscopy (LBSL).¹ We report a 2.5-year-old boy, who developed regression in motor abilities and variability of playing, irritability, forced after a respiratory infection with fever. At the age of 10 months, he showed delayed fixation, severe irritability, and no active moving with muscular hypotonia. Cerebral MRI marked symmetrical hyperdensity of the supratentorial white matter. No lactate elevation was observed in CSF or blood. The neurological state improved continually over the months. The boy shows only a slight ataxia at 2.5 years. The cerebral MRI at the age of 14 months showed an augmented alteration of the supratentorial white matter in contrast to the good clinical recovery. A homozygous mutation in the DARS2 gene (heterozygous in the consanguineous parents) is most probably the cause of the disease.

In literature, more often combined heterozygous mutations in the DARS2 gene with a common phenotype characterized by later onset and slow neurological deterioration are reported. We present an infant with primarily supratentorial leukoencephalopathy because of homozygous DARS2 mutation aggravated by a febrile infection with up to now good neurological outcome beside persisting alteration of the white matter signal.

Keywords: mitochondriopathy, leukoencephalopathy, DARSS2 mutation.

References

References

1 van Berge L et al. Leukencephalopathy with brain stem and spinal cord involvement and lactate elevaton: clinical and genetic characterization and target for. Brain 2014;1019–1029