A Korean child diagnosed with malonic aciduria harboring a novel start codon mutation following presentation with dilated cardiomyopathy

Background Malonic aciduria (MA, OMIM#248360) is an extremely rare inherited metabolic disorder caused by the deficiency of malonyl‐CoA decarboxylase. The phenotype exhibited by patients with MA is variable, but may include symptoms, such as developmental delay in early childhood, seizures, vomiting, metabolic acidosis, hypoglycemia, ketosis, and cardiomyopathy. We describe the first case of a Korean child with MA who presented with dilated cardiomyopathy (DCMP) at the age of 3 months. Methods and Results A 3‐month‐old Korean boy visited our hospital for diagnosis and management of cardiomegaly. Newborn screening for inherited metabolic diseases showed a normal result; therefore, DCMP management was initiated. Biochemical and the MLYCD gene analyses subsequently confirmed diagnosis of MA. Elevated plasma C3DC level and excessive excretion of urinary malonate were observed, and two pathogenic variants, including a novel start codon mutation (c.1A>G), were identified in MLYCD. A low long‐chain fat diet with middle‐chain triglyceride formula and L‐carnitine supplementation was initiated. The patient is now 5 years old and exhibits considerably improved cardiac function. Conclusions MA can be diagnosed using newborn screening; however, negative results do not exclude the possibility of disease. Metabolic screening for differential diagnosis of infantile DCMP is recommended to rule out rare, but manageable, metabolic cardiomyopathies. This is the first report of MA diagnosed in a patient following presentation with infantile‐onset dilated cardiomyopathy following negative malonylcarnitine measurement results in a newborn screening program. The disease was successfully managed with a combination of medical therapy and dietary intervention.