Cor Vasa 2023, 65(3):538-544 | DOI: 10.33678/cor.2022.116

(PRKAG2 syndrome as a highly arrhythmogenic eventuality in the differential diagnosis of hypertrophic cardiomyopathy - an example of two families with a confirmed causative DNA variant)

Markéta Hodboďová^a, Alice Krebsová^{b, e}, Petra Peldová^{d, f}, Rostislav Polášek^{a, c}, Tomáš Roubíček^{a, b, c}

^a Kardiocentrum, Krajská nemocnice Liberec, a.s., Liberec

^b Centrum dědičných kardiovaskulárních onemocnění, Klinika kardiologie, Institut klinické a experimentální medicíny, Praha

^c Fakulta zdravotnických studií, Technická univerzita Liberec, Liberec

^d Ústav biologie a lékařské genetiky, Fakultní nemocnice Motol, Praha

^e Member of the European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart (ERN GUARD- -Heart), Praha

^f Member of the European Reference Network on Intellectual Disability and Congenital Malformation (ITHAKA), Praha

Hypertrophic cardiomyopathy (HCM) affects 0.2% of the population and is the most common form of hereditary heart muscle disease in adults. The most frequent cause of HCM are changes in the genes encoding sarcomere proteins. However, up to 10% of patients are affected by another type of systemic genetic dis- ease that has myocardial hypertrophy as only one of its multi-organ manifestations. Among these diseases is PRKAG2 glycogenosis, a rare metabolic storage disorder caused by an inherited defect in the γ2 regulatory subunit of adenosine monophosphate-activated protein kinase (AMPK). In addition to skeletal muscle myopathy, it causes HCMP with a high risk of malignant ventricular and supraventricular arrhythmias and several conduction disorders. Thanks to close collaboration of several departments, we diagnosed two families with a causative DNA variant in the PRKAG2 gene. On the basis of the presented case studies, we document highly variable manifestations of PRKAG2 syndrome and thus highlight the pitfalls in its clinical diagnosis and therapy.

Keywords: Conduction disease, Hypertrophic cardiomyopathy, Pre-excitation, PRKAG2 syndrome, Sudden cardiac death, Supraventricular arrhythmias

Received: September 15, 2022; Revised: October 19, 2022; Accepted: November 7, 2022; Published: June 20, 2023  Show citation