ALPK3-associated Cardiomyopathy (QF_FR_108)

A 37-year-old male patient presented for chest pain with ST-elevations in V2-V5. He was taken emergently to the cath lab where coronary angiography revealed an anomalous origin of the right coronary artery from the left sinus of Valsalva, but otherwise unremarkable coronaries. An echocardiogram was performed which revealed moderate concentric left ventricular hypertrophy. A patch ECG monitor showed paroxysmal atrial fibrillation. Given his young age, the patient was sent for genetic testing which showed a heterozygous variant of unknown significance in the ALPK3 gene (c.2195G >A). As mutations in ALPK3 can be associated with hypertrophic cardiomyopathy and dilated cardiomyopathy, he was sent for cardiac MRI for further workup.

Diagnostic Techniques and Their Most Important Findings:

Cardiac MRI showed a mild biventricular dilation with normal biventricular systolic function. There was mild asymmetric septal left ventricular hypertrophy (LVH) measuring up to 12 mm in the basal anteroseptal wall at end-diastole. There was no evidence of left ventricular outflow tract obstruction at rest. T1 and T2 relaxation times were within normal limits. There was patchy subepicardial/mid-myocardial late gadolinium enhancement (LGE) along the apical inferior, apical anterior, apical septal, and apical lateral walls. There were additional small foci of LGE noted in the mid-basal anteroseptal and inferoseptal walls. Review of case reports of ALPK3-associated cardiomyopathy showed a similar, though more prominent, pattern of LGE, raising the suspicion that our patient may have an early manifestation of this newer entity.

Learning Points from this Case:

The ALPK3 gene encodes alpha-kinase 3, a cardiomyocyte specific protein. Mutations in ALPK3 have been been shown to cause both dilated cardiomyopathy and hypertrophic cardiomyopathy. We present a case of a young patient with an ALPK3 mutation with findings of atrial fibrillation, anomalous origin of the right coronary artery, mild asymmetric septal LVH, biventricular dilation, and patchy subepicardial/mid-myocardial LGE along the apical and septal walls.