Leukoencephalopathy with cysts and hyperglycinemia may result from NFU1 deficiency
Résumé
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.
Mots clés
Humans
Female
Europe
Protein Processing
Post-Translational
Child
Preschool
Fibroblasts/enzymology
Carrier Proteins/*genetics
Cerebrospinal Fluid/chemistry
Cysts/*genetics
Lactates/analysis
Leukoencephalopathies/*genetics
Mitochondrial Diseases/metabolism
Plasma/chemistry
Propionic Acidemia/*genetics
Proteins/chemistry
Pyruvate Dehydrogenase Complex Deficiency Disease/metabolism
Urine/chemistry