Unusual presentation of propionic acidaemia as isolated cardiomyopathy

Propionic acidaemia (PA) is an autosomal recessive disease that results from deficiency of propionyl-CoA carboxylase (PCC). In the majority of reported cases, the phenotype includes metabolic acidosis and/or neurological deficits. We report on a 14-year-old Asian-American male with PA who presented with isolated cardiomyopathy without any documented episodes of metabolic acidosis or evidence of any neurocognitive deficits. On routine metabolic screening, the patient was found to have urine organic acids suggestive of PA. Biochemical and genetic characterization confirmed a PCC deficiency with two novel mutations in PCCB: IVS7 + 2 T > G (c.763 + 2 T > G) and p.R410Q (c.1229 G > A). Residual enzyme activity likely explains our patient's mild phenotype. Splicing mutations tend to result in a milder phenotype as these mutations may still produce small amounts of normal enzyme. In addition, the similar p.R410W mutation has been shown to have partial residual activity. Moreover, this case illustrates that a thorough metabolic evaluation should be performed in both paediatric and adult patients with cardiomyopathy. Such an evaluation has important implications for clinical management and genetic counselling.