A LATE PRIMARY CARNITINE DEFICIENCY DIAGNOSIS IN ADULTHOOD DURING ARRHYTHMIC RISK REASSESSMENT IN HYPERTROPHIC CARDIOMYOPATHY

Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease, typically caused by mutations in cardiac sarcomere protein genes. Inborn errors of metabolism are a rare cause of this condition, usually diagnosed in infancy due to severe heart failure and concurrent extracardiac manifestations.

A 36–year–old female patient, diagnosed with non–obstructive HCM at the age of 9 due to heart failure, was treated with beta–blockers and ACE inhibitors. During the follow up she remained stable in NYHA class I, family screening was positive but genetic analysis has never been performed due to parents and patient’s refusal. At the latest echocardiographic evaluation (August 2023), a slight reduction in ejection fraction (from 50% to 40%) was observed, with akinesia of the IVS and the inferior wall, in the presence of known asymmetric hypertrophy. Based on this finding, a CMR was performed, which compared to the previous one conducted 3 years earlier, confirmed the reduction in ejection fraction and showed an increase in left ventricular volumes and a significant worsening of LGE areas. Additionally, a cardiopulmonary exercise test was performed, revealing a reduced VO2max of 15 l/min. To assess the risk of sudden cardiac death, an HCM Risk–SCD calculation was performed, yielding a result indicating a mild risk (3.19%). Considering the rapid disease progression, a family history of sudden cardiac death, and increased isolated ventricular extrasystoles from recent Holter monitoring, a S–ICD was implanted. Simultaneously, the patient agreed to genetic testing, revealing an exon 5 SLC22A5 gene mutation, suggesting autosomal recessive primary carnitine deficiency, a rare metabolic disorder usually causing early heart failure and several extracardiac manifestation, none of which the patient exhibited. In our case, uncovering this finding leads to two significant therapeutic implications: a major appropriateness of implanting an ICD, as the HCM Risk–SCD is not applicable in metabolic forms of HCM, and the need to initiate oral carnitine supplementation therapy to halt the progression of the disease. This evidence underscores the importance of personalised arrhythmic risk assessment in HCM patient evaluations and the necessity to exclude atypical metabolic causes of HCM, even if unlikely, given the significant therapeutic implications that may arise.