Leukoencephalopathy with cysts and hyperglycinemia may result from NFU1 deficiency.
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.
Reference Center of Inherited Metabolic Diseases, University Paris Descartes, Hospital Necker Enfants Malades, APHP, Paris, France.
Mathilde
M
Nizon
Department of Biochemistry, Hospital Bicêtre, Le Kremlin Bicêtre, France.
Audrey
A
Boutron
Department of Pediatric Radiology, University Paris Descartes, Hospital Necker Enfants Malades, Paris, France.
Nathalie
N
Boddaert
Department of Biochemistry, Hospital Bicêtre, Le Kremlin Bicêtre, France.
Abdelhamid
A
Slama
Department of Molecular Genetics, CNRS UMR 5535, Montpellier, France.
Hélène
H
Delpech
Department of Molecular Genetics, CNRS UMR 5535, Montpellier, France.
Claude
C
Sardet
Reference Center of Inherited Metabolic Diseases, University Paris Descartes, Hospital Necker Enfants Malades, APHP, Paris, France.
Anaïs
A
Brassier
Reference Center of Inherited Metabolic Diseases, University Paris Descartes, Hospital Necker Enfants Malades, APHP, Paris, France; Department of Biochemistry, University Paris Descartes, Hospital Necker Enfants Malades, Paris, France.
Florence
F
Habarou
Paris-Sud University, CNRS-UMR8621, Genetics and Microbiology Institute, Orsay, France.
Agnès
A
Delahodde
Department of Biochemistry, Hospital Bicêtre, Le Kremlin Bicêtre, France.
Isabelle
I
Correia
Reference Center of Inherited Metabolic Diseases, University Paris Descartes, Hospital Necker Enfants Malades, APHP, Paris, France; Department of Biochemistry, University Paris Descartes, Hospital Necker Enfants Malades, Paris, France.
Chris
C
Ottolenghi
Reference Center of Inherited Metabolic Diseases, University Paris Descartes, Hospital Necker Enfants Malades, APHP, Paris, France. Electronic address: pascale.delonlay@nck.aphp.fr.
Pascale
P
de Lonlay
D002352:Carrier Proteins / Q000235:genetics*; D002555:Cerebrospinal Fluid / Q000737:chemistry; D002675:Child, Preschool; D003560:Cysts / Q000235:genetics*; D005060:Europe; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D007773:Lactates / Q000032:analysis; D056784:Leukoencephalopathies / Q000235:genetics*; D028361:Mitochondrial Diseases / Q000378:metabolism; D010949:Plasma / Q000737:chemistry; D056693:Propionic Acidemia / Q000235:genetics*; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000737:chemistry; D015325:Pyruvate Dehydrogenase Complex Deficiency Disease / Q000378:metabolism; D014556:Urine / Q000737:chemistry
D002352:Carrier Proteins; D007773:Lactates; C426067:NFU1 protein, human; D011506:Proteins
Hyperglycinemia; Leucoencephalopathy with cysts; Lipoic acid; NFU1; Pyruvate dehydrogenase deficiency