title: Malonyl-CoA decarboxylase deficiency: long-term follow-up of a patient new clinical features and novel mutations.
abstract: BACKGROUND
  Malonyl-CoA decarboxylase (MLYCD, EC 4.1.1.9) deficiency is a rare autosomal recessive disorder that is widely diagnosed by neonatal screening.
  
  
  METHODS
  We report long term follow up of a patient with MLYCD deficiency showing signs of neonatal hypoglycemia, mental retardation, developmental delay and rheumatoid arthritis. Brain MRI revealed patchy, symmetrical hyperintensity of the deep white matter with periventricular white matter and subcortical arcuate fibers being spared. MLCYD gene sequence analysis was done to identify possible mutations. Expression analyses at mRNA and protein levels were also performed. Further, immunocytochemical studies were implemented to check for its subcellular localization.
  
  
  RESULTS
  MLYCD gene sequencing identified a novel compound heterozygous mutation (c.22 T>A, p.M1K, c.454 C>A; pH152N) in our patient and a heterozygous mutation in the healthy mother c.22 T>A; pM1K. Reduced expression of RNA and protein levels was observed. Immunocytochemical analysis showed diffused staining across the cytoplasm with apparent signs of intracellular mislocalization to the nucleus. RESULTS also indicated subcellular colocalization of MLCYD with mitochondria was scant compared to control.
  
  
  CONCLUSIONS
  Our patient was identified with a novel compound heterozygous MLYCD mutation at the N-terminal helical domain. This study indicates that protein mislocalization is a characteristic feature of MLYCD deficiency in our patient.
authors.affiliation: Research Program of Molecular Neurology, Biomedicum 1, University of Helsinki, Helsinki, Finland. Electronic address: padmini.polinati@helsinki.fi.
authors.forename: Padmini P
authors.initials: PP
authors.lastname: Polinati
authors.affiliation: Children Hospital, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Leena
authors.initials: L
authors.lastname: Valanne
authors.affiliation: Research Program of Molecular Neurology, Biomedicum 1, University of Helsinki, Helsinki, Finland; Children Hospital, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Tiina
authors.initials: T
authors.lastname: Tyni
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D001483:Base Sequence; D015153:Blotting, Western; D002262:Carboxy-Lyases / Q000172:deficiency* / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008316:Malonyl Coenzyme A / Q000235:genetics; D008661:Metabolism, Inborn Errors / Q000235:genetics* / Q000503:physiopathology; D008764:Methylmalonic Acid; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction
chemical_list: D008316:Malonyl Coenzyme A; D008764:Methylmalonic Acid; D002262:Carboxy-Lyases; C021532:malonyl-CoA decarboxylase
keywords: Low fat diet therapy; Malonyl CoA decarboxylase; Mental retardation; Mitochondrial disorder; Rheumatoid arthritis