Discussion

Dilated cardiomyopathy) can be the consequence of clearly defined external aetiologic factors, such as viral infections, toxins, drugs, and genetic metabolic disorders. At least 30–40% of cases have a prevalent genetic origin, and in the remaining part, genetics may still play an important role. DCM is the most common form of childhood cardiomyopathy and the most frequent reason for cardiac transplantation. With the expansion of clinical genetic testing, genetic causes of DCM have been increasingly identified. Metabolic screening for the differential diagnosis of childhood DCM is recommended to rule out rare, but treatable reasons for inherited metabolic disorders as malonic aciduria.^{Reference Jammal Addin, Young, McCarrison and Hunter4}

Malonic aciduria (OMIM 248,360), or malonyl coenzyme A decarboxylase deficiency, is a rare autosomal recessive inborn error of fatty acid metabolism characterised by developmental delay, excretion of excess malonic and methylmalonic acids in urine, metabolic acidosis, hypoglycaemia, seizure disorder, and cardiomyopathy. Increased malonyl-CoA levels potently inhibit long-chain carnitine acyltransferases. It has been demonstrated that malonic aciduria is due to deficiency of malonyl-CoA decarboxylase that catalyses the decarboxylation of malonyl-CoA to acetyl-CoA.^{Reference Polinati, Valanne and Tyni5} Malonyl-CoA represents the first committed step in fatty acid biosynthesis and serves as an important regulatory role through inhibition of carnitine palmitoyltransferase-I.^{Reference Peng, Wu, Zhou, Zhong and Yin6} Accumulation of malonyl-CoA caused by MCD deficiency prevents entry of cytoplasmic acyl-CoA into mitochondria and peroxisomes by inhibiting CPT-I, thus decreasing β-oxidation of fatty acids and thus decrease β-oxidation of fatty acids in both mitochondria and peroxisomes. MLYCD has a tissue-specific expression pattern^{Reference Prada, Jefferies and Grenier7} with the highest message levels in heart muscle, skeletal muscle, brain, small intestine, liver, kidney, and pancreas. MLYCD is routinely screened for in 50% of NBS state programmes; malonyl carnitine (C3-DC) measurement is possible and will allow neonatal diagnosis of patients with MCD deficiency.^{Reference Baertling, Mayatepek and Thimm8}

Nearly 50 different molecular mutations in the MLYCD gene have been identified so far according to the ClinVar database. These mutations are generally deletions, frameshift, and nonsense mutations that seriously alter the protein structure. We also detected a novel nonsense mutation in the 1st exon of the MLYCD gene.^{Reference Lee, Ko, Song, Song and Park3}

A recent report suggests that cardiomyopathy occurs in approximately 40% of cases and the phenotypic similarity with fatty acid oxidation defects is highlighted by other authors. Biochemically, it is characterised by elevated urinary excretion of malonic and methylmalonic acids and raised malonylcarnitine in blood. MCD catalyses the conversion of malonyl-CoA to acetyl-CoA and regulates the intracellular concentration of malonyl-CoA. As malonyl-CoA inhibits carnitine palmitoyltransferase 1, MCD indirectly inhibits mitochondrial fatty acid oxidation.^{Reference Lee, Ko, Song, Song and Park3,Reference Xue, Peng and Zhou9,Reference Ersoy, Akyol, Ceylaner and Çakır Biçer10} We observed the improvement in cardiac function, as shown by serial echocardiography, following the introduction of a dietary therapy and L-carnitine. The diet is similarly high in carbohydrates. Several children have been treated with a low-fat, high-MCT, and high-carbohydrate diet with improvement in the clinical condition when the diet was modified before significant disease symptoms. Our findings also expand the number of reported cases and provide additional information towards the MLCYD mutation database.