Marcu Andreea Sorina, Vătăşescu Radu, Onciul Sebastian, Rădoi Viorica, Jurcuţ Ruxandra
Expert Center for Genetic Cardiovascular Diseases, Emergency Institute for Cardiovascular Diseases, 258 Fundeni Street, 022328 Bucharest, Romania.
Cardiology Department, Emergency Clinical County Hospital Craiova, 1 Tabaci Street, 200642 Craiova, Romania.
Life (Basel). 2022 Dec 18;12(12):2136. doi: 10.3390/life12122136.
PRKAG2 syndrome (PS) is a rare, early-onset autosomal dominant phenocopy of sarcomeric hypertrophic cardiomyopathy (HCM), that mainly presents with ventricular pre-excitation, cardiac hypertrophy and progressive conduction system degeneration. Its natural course, treatment and prognosis are significantly different from sarcomeric HCM. The clinical phenotypes of PRKAG2 syndrome often overlap with HCM due to sarcomere protein mutations, causing this condition to be frequently misdiagnosed. The syndrome is caused by mutations in the gene encoding for the γ2 regulatory subunit (PRKAG2) of 5′ Adenosine Monophosphate-Activated Protein Kinase (AMPK), an enzyme that modulates glucose uptake and glycolysis. PRKAG2 mutations (OMIM#602743) are responsible for structural changes of AMPK, leading to an impaired myocyte glucidic uptake, and finally causing storage cardiomyopathy. We describe the clinical and investigative findings in a family with several affected members (NM_016203.4:c.905G>A or p.(Arg302Gln), heterozygous), highlighting the various phenotypes even in the same family, and the utility of genetic testing in diagnosing PS. The particularity of this family case is represented by the fact that the index patient was diagnosed at age 16 with cardiac hypertrophy and ventricular pre-excitation while his mother, by age 42, only had Wolff−Parkinson−White syndrome, without left ventricle hypertrophy. Both the grandmother and the great-grandmother underwent pacemaker implantation at a young age because of conduction abnormalities. Making the distinction between PS and sarcomeric HCM is actionable, given the early-onset of the disease, the numerous life-threatening consequences and the high rate of conduction disorders. In patients who exhibit cardiac hypertrophy coexisting with ventricular pre-excitation, genetic screening for PRKAG2 mutations should be considered.
PRKAG2综合征（PS）是一种罕见的、早发性的常染色体显性遗传的肌节性肥厚型心肌病（HCM）表型模拟症，主要表现为心室预激、心脏肥大和进行性传导系统退变。其自然病程、治疗和预后与肌节性HCM显著不同。由于肌节蛋白突变，PRKAG2综合征的临床表型常与HCM重叠，导致该病经常被误诊。该综合征由5′-单磷酸腺苷激活蛋白激酶（AMPK）的γ2调节亚基（PRKAG2）编码基因的突变引起，AMPK是一种调节葡萄糖摄取和糖酵解的酶。PRKAG2突变（OMIM#602743）导致AMPK结构改变，导致心肌细胞葡萄糖摄取受损，最终引起贮积性心肌病。我们描述了一个有多个患病成员（NM_016203.4:c.905G>A或p.(Arg302Gln)，杂合子）的家庭的临床和检查结果，强调了即使在同一个家庭中也存在各种表型，以及基因检测在诊断PS中的作用。这个家庭病例的特殊性在于，索引患者16岁时被诊断为心脏肥大和心室预激，而他的母亲42岁时仅患有 Wolff-Parkinson-White综合征，无左心室肥大。祖母和曾祖母都因传导异常在年轻时接受了起搏器植入。鉴于该疾病的早发性、众多危及生命的后果和高传导障碍发生率，区分PS和肌节性HCM是可行的。对于表现为心脏肥大与心室预激并存的患者，应考虑进行PRKAG2突变的基因筛查。
