Leukoencephalopathy with cysts and hyperglycinemia may result from NFU1 deficiency

Mitochondrion. 2014 Mar;15:59-64. doi: 10.1016/j.mito.2014.01.003. Epub 2014 Jan 22.


Lipoic acid metabolism defects are new metabolic disorders that cause neurological, cardiomuscular or pulmonary impairment. We report on a patient that presented with progressive neurological regression suggestive of an energetic disease, involving leukoencephalopathy with cysts. Elevated levels of glycine in plasma, urine and CSF associated with intermittent increases of lactate were consistent with a defect in lipoic acid metabolism. Support for the diagnosis was provided by pyruvate dehydrogenase deficiency and multiple mitochondrial respiratory chain deficiency in skin fibroblasts, as well as no lipoylated protein by western blot. Two mutations in the NFU1 gene confirmed the diagnosis. The p.Gly208Cys mutation has previously been reported suggesting a founder effect in Europe.

Keywords: Hyperglycinemia; Leucoencephalopathy with cysts; Lipoic acid; NFU1; Pyruvate dehydrogenase deficiency.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins / genetics*
  • Cerebrospinal Fluid / chemistry
  • Child, Preschool
  • Cysts / genetics*
  • Europe
  • Female
  • Fibroblasts / enzymology
  • Humans
  • Lactates / analysis
  • Leukoencephalopathies / genetics*
  • Mitochondrial Diseases / metabolism
  • Plasma / chemistry
  • Propionic Acidemia / genetics*
  • Protein Processing, Post-Translational
  • Proteins / chemistry
  • Pyruvate Dehydrogenase Complex Deficiency Disease / metabolism
  • Urine / chemistry


  • Carrier Proteins
  • Lactates
  • NFU1 protein, human
  • Proteins