Malonyl-CoA decarboxylase deficiency: long-term follow-up of a patient new clinical features and novel mutations

Brain Dev. 2015 Jan;37(1):107-13. doi: 10.1016/j.braindev.2014.02.001. Epub 2014 Mar 7.


Background: Malonyl-CoA decarboxylase (MLYCD, EC 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.

Conclusion: 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.

Keywords: Low fat diet therapy; Malonyl CoA decarboxylase; Mental retardation; Mitochondrial disorder; Rheumatoid arthritis.

Publication types

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

MeSH terms

  • Adolescent
  • Age of Onset
  • Base Sequence
  • Blotting, Western
  • Carboxy-Lyases / deficiency*
  • Carboxy-Lyases / genetics
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Female
  • Humans
  • Immunohistochemistry
  • Infant
  • Malonyl Coenzyme A / genetics
  • Metabolism, Inborn Errors / genetics*
  • Metabolism, Inborn Errors / physiopathology
  • Methylmalonic Acid
  • Molecular Sequence Data
  • Mutation
  • Polymerase Chain Reaction


  • Malonyl Coenzyme A
  • Methylmalonic Acid
  • Carboxy-Lyases
  • malonyl-CoA decarboxylase

Supplementary concepts

  • Malonic aciduria