OBJECTIVEThe gamma(2) subunit of AMP-activated protein kinase (PRKAG2) located in chromosome 7 plays an important role in regulating metabolic pathways, and patients with PRKAG2 mutations are associated with familial ventricular pre-excitation, hypertrophic cardiomyopathy and AV block. We observed the difference on the phenotypes in a large family with same PRKAG2 mutation.

METHODDirect DNA sequence was performed to screen the exons and exon-intron boundaries of PRKAG2 gene in a large family with 13 affected persons detected by electrocardiography (ECG).

RESULTSSinus bradycardia, short PR interval, right bundle bunch block (RBBB), complete AV block, atrial flutter, atrial fibrillation and sudden cardiac death were identified in this family. Hypertrophic cardiomyopathy was found in one family member. Genetic analysis revealed a missense mutation (Arg302Glu) in all affected family members. This mutation was previous described in patients with Wolff-Parkinson-White (WPW) syndrome and hypertrophic cardiomyopathy.

CONCLUSIONSBesides WPW syndrome and hypertrophic cardiomyopathy, PRKAG2 mutations are responsible also for a diverse phenotypes. PRKAG2 gene mutation should be suspected with familial occurrence of RBBB, sinus bradycardia, and short PR interval.

AMP-Activated Protein Kinases ; genetics ; Arrhythmias, Cardiac ; genetics ; Brazil ; Female ; Genotype ; Humans ; Male ; Mutation ; Pedigree ; Phenotype ; Pre-Excitation Syndromes ; etiology

Objective: To review the clinical data of 7 patients with Danon disease and analyze their clinical characteristics. Methods: The medical records of 7 patients with Danon disease, who were hospitalized in Peking Union Medical College Hospital of Chinese Academy of Medical Sciences from April 2008 to July 2021, were reviewed and summarized, of which 6 cases were diagnosed as Danon disease by lysosomal-associated membrane protein-2 (LAMP-2) gene mutation detection and 1 case was diagnosed by clinicopathological features. Clinical manifestations, biochemical indexes, electrocardiogram, echocardiography, skeletal muscle and myocardial biopsy and gene detection results were analyzed, and patients received clinical follow-up after discharge. Results: Six patients were male and average age was (15.4±3.5) years and the average follow-up time was (27.7±17.0) months. The main clinical manifestations were myocardial hypertrophy (6/7), decreased myodynamia (2/7) and poor academic performance (3/7). Electrocardiogram features included pre-excitation syndrome (6/7) and left ventricular hypertrophy (7/7). Echocardiography examination evidenced myocardial hypertrophy (6/7), and left ventricular dilatation and systolic dysfunction during the disease course (1/7). The results of skeletal muscle biopsy in 6 patients were consistent with autophagy vacuolar myopathy. Subendocardial myocardial biopsy was performed in 3 patients, and a large amount of glycogen deposition with autophagosome formation was found in cardiomyocytes. LAMP-2 gene was detected in 6 patients, and missense mutations were found in all these patients. During the follow-up period, implantable cardioverter defibrillator implantation was performed in 1 patient because of high atrioventricular block 4 years after diagnosis, and there was no death or hospitalization for cardiovascular events in the other patients. Conclusion: The main clinical manifestations of Danon disease are cardiomyopathy, myopathy and mental retardation. Pre-excitation syndrome is a common electrocardiographic manifestation. Autophagy vacuoles can be seen in skeletal muscle and myocardial pathological biopsies. LAMP-2 gene mutation analysis is helpful in the diagnose of this disease.
Adolescent ; Child ; Female ; Humans ; Male ; Cardiomyopathies/etiology* ; Glycogen Storage Disease Type IIb/complications* ; Hypertrophy, Left Ventricular/etiology* ; Lysosomal-Associated Membrane Protein 2/genetics* ; Pre-Excitation Syndromes/genetics*