Malonyl Coenzyme A Decarboxylase Deficiency: Early Dietary Restriction and Time Course of Cardiomyopathy
ABSTRACT Malonyl coenzyme A (CoA) decarboxylase (MCD) deficiency is a rare autosomal recessive organic acidemia characterized by varying degrees of organ involvement and severity. MCD regulates fatty acid biosynthesis and converts malonyl-CoA to acetyl-CoA. Cardiomyopathy is 1 of the leading causes of morbidity and mortality in this disorder. It is unknown if diet alone prevents cardiomyopathy development based in published literature. We report a 10-month-old infant girl identified by newborn screening and confirmed MCD deficiency with a novel homozygous MLYCD mutation. She had normal echocardiogram measurements before transition to high medium-chain triglycerides and low long-chain triglycerides diet. Left ventricular noncompaction development was not prevented by dietary interventions. Further restriction of long-chain triglycerides and medium-chain triglycerides supplementation in combination with angiotensin-converting enzyme inhibitors helped to improve echocardiogram findings. Patient remained asymptomatic, with normal development and growth. Our case emphasizes the need for ongoing cardiac disease screening in patients with MCD deficiency and the benefits and limitations of current dietary interventions.
- International journal of cardiology 02/2013; 168(1). DOI:10.1016/j.ijcard.2013.01.221 · 6.18 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Background: Malonyl-CoA decarboxylase (MLYCD, EC 126.96.36.199) 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.Brain & development 01/2014; 37(1). DOI:10.1016/j.braindev.2014.02.001 · 1.54 Impact Factor
- International journal of cardiology 03/2014; 173(3). DOI:10.1016/j.ijcard.2014.03.025 · 6.18 Impact Factor