Early-onset leukoencephalopathy due to a homozygous missense mutation in the DARS2 gene.
Mutations in the DARS2 gene are known to cause leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL), a rare autosomal recessive neurological disorder. It was originally described as juvenile-onset slowly progressive ataxia and spasticity, but recent reports suggest a broader clinical spectrum. Most patients were found to carry compound heterozygous DARS2 mutations, and only very few patients with homozygous mutations have been described so far. We present here an 8-month-old boy carrying a homozygous missense mutation in DARS2 who clinically showed severe neurological deterioration after a respiratory tract infection, followed by an almost complete remission of symptoms. This report further extends the knowledge about the clinical and molecular genetic spectrum of LBSL.
Department of Neuropediatrics, University Children's Hospital, Ruhr-University Bochum, Germany. Electronic address: c.koehler@klinikum-bochum.de.
Cornelia
C
Köhler
Institute of Pediatric Radiology, University Children's Hospital, Ruhr-University Bochum, Germany.
Christoph
C
Heyer
Department of Human Genetics, Ruhr-University Bochum, Germany.
Sabine
S
Hoffjan
Department of Human Genetics, Ruhr-University Bochum, Germany.
Susanne
S
Stemmler
Department of Neuropediatrics, University Children's Hospital, Ruhr-University Bochum, Germany.
Thomas
T
Lücke
Department of Neuropediatrics, University Children's Hospital, Ruhr-University Bochum, Germany.
Charlotte
C
Thiels
University Medical Center Hamburg, Germany.
Alfried
A
Kohlschütter
Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Ulrike
U
Löbel
Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Newcastle Upon Tyne, Great Britain, UK.
Rita
R
Horvath
Medical Genetics Centre, Munich, Germany.
Stephanie
S
Kleinle
Medical Genetics Centre, Munich, Germany.
Anna
A
Benet-Pages
Medical Genetics Centre, Munich, Germany.
Angela
A
Abicht
D017668:Age of Onset; D001226:Aspartate-tRNA Ligase / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D007223:Infant; D056784:Leukoencephalopathies / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D017422:Sequence Analysis, DNA
D001226:Aspartate-tRNA Ligase; C558608:DARS2 protein, human
DARS2; LBSL; Leukoencephalopathy; Magnetic resonance imaging; Mitochondriopathy