Discussion

Paediatric hypertrophic cardiomyopathy is distinguished from adult hypertrophic cardiomyopathy in terms of several aspects. The incidence of paediatric hypertrophic cardiomyopathy is relatively low. Moreover, its aetiology is limited to idiopathic conditions, and its signs and symptoms are relatively vague.^{Reference Seok and Oh2} In a Korean study, the prevalence of hypertrophic cardiomyopathy was 0.51/100,000 children aged younger than 15 years, and the survival rates of children aged over 9 years was 90.3%.^{Reference Oh, Hong and Choi5} In the infantile period, the prognosis of hypertrophic cardiomyopathy is relatively poor, with a mortality or transplantation rate of approximately 30%.^{Reference Seok and Oh2}

Hypertrophic cardiomyopathy is frequently observed among neonates born to mothers with diabetes mellitus.^{Reference Hornberger1} However, most infants with hypertrophic cardiomyopathy are clinically asymptomatic, and the condition spontaneously regresses within a few months and resolves at 1 year of age.^{Reference Hornberger1} In our case, the patient underwent echocardiography due to a history of maternal diabetes mellitus and found the progressive left ventricular hypertrophy. Thus, genetic surveillance was performed to assess other genetic causes and found m.3243A>G mutation in a mitochondrial tRNA leucine 1 gene.

The m.3243A>G mutation in a mitochondrial tRNA leucine 1 gene, located at seven base pairs away from the D loop of the tRNA^Leu(UUR) molecule, was the well-characterized pathogenic gene of mitochondrial cardiomyopathy. The m.3243A>G mutation is found in approximately 80% of patients with MELAS syndrome, and it is commonly a maternally transmitted mutation.^{Reference Brambilla, Favilli and Olivotto4} Up to 56–75% of adult patients with mitochondriopathy associated with m.3243A>G presented with hypertrophic cardiomyopathy.^{Reference Holmgren, Wåhlander, Eriksson, Oldfors, Holme and Tulinius6} In paediatric patients with mitochondrial disease, cardiomyopathy is observed in approximately 20% and its onset and severity remarkably vary. That is, some patients die at an early postnatal age, and others show gradual progression during the adolescent period. The paediatric-onset cardiomyopathy is associated with poor prognosis, with 10-year survival rates of 67%.^{Reference Imai-Okazaki, Kishita and Kohda7,Reference Wortmann, Rodenburg, Backx, Schmitt, Smeitink and Morava8} In our case, hypertrophic cardiomyopathy was related with m.3243A>G mutation. However, the patient was not definitely diagnosed with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like syndrome as he died before presenting with other clinical manifestations, such as developmental delay, muscle weakness, and epilepsy. The hypertrophic cardiomyopathy was the initial and only clinical presentation of his mitochondrial cardiomyopathy.

In conclusion, hypertrophic cardiomyopathy associated with m.3243A>G mutation in a mitochondrial tRNA leucine 1 gene is extremely rare among neonates. Nevertheless, due to cardiac involvement, the condition has a poor prognosis. Therefore, in patients diagnosed with neonatal hypertrophic cardiomyopathy, special surveillance must be performed for genetic diagnosis, and active intervention is required, even though the patient was born to a diabetic mother.