RESUMO
We describe a new type of cardiomyopathy caused by a mutation in the glycogenin-1 gene (GYG1). Three unrelated male patients aged 34 to 52 years with cardiomyopathy and abnormal glycogen storage on endomyocardial biopsy were homozygous for the missense mutation p.Asp102His in GYG1. The mutated glycogenin-1 protein was expressed in cardiac tissue but had lost its ability to autoglucosylate as demonstrated by an in vitro assay and western blot analysis. It was therefore unable to form the primer for normal glycogen synthesis. Two of the patients showed similar patterns of heart dilatation, reduced ejection fraction and extensive late gadolinium enhancement on cardiac magnetic resonance imaging. These two patients were severely affected, necessitating cardiac transplantation. The cardiomyocyte storage material was characterized by large inclusions of periodic acid and Schiff positive material that was partly resistant to alpha-amylase treatment consistent with polyglucosan. The storage material had, unlike normal glycogen, a partly fibrillar structure by electron microscopy. None of the patients showed signs or symptoms of muscle weakness but a skeletal muscle biopsy in one case revealed muscle fibres with abnormal glycogen storage. Glycogenin-1 deficiency is known as a rare cause of skeletal muscle glycogen storage disease, usually without cardiomyopathy. We demonstrate that it may also be the cause of severe cardiomyopathy and cardiac failure without skeletal muscle weakness. GYG1 should be included in cardiomyopathy gene panels.
Assuntos
Cardiomiopatias/genética , Glucosiltransferases/deficiência , Glucosiltransferases/genética , Glicoproteínas/deficiência , Glicoproteínas/genética , Mutação de Sentido Incorreto/genética , Adulto , Biópsia , Glucanos/genética , Glicogênio/genética , Doença de Depósito de Glicogênio/genética , Homozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/metabolismoRESUMO
BACKGROUND: The utility of three-dimensional echocardiography (3DE) for right ventricular (RV) assessment is uncertain in older children and adults with congenital heart disease (CHD), in whom the right ventricle is often dilated and dysfunction is common. METHODS: RV assessments using 3DE were compared with manual tracing and automated border detection (ABD) with magnetic resonance imaging (MRI) as the reference method. Twenty-eight of 54 consecutive patients (52%; median age, 17 years) with CHD had adequate three-dimensional echocardiographic data sets for analysis. RESULTS: There were wide ranges of RV size (mean RV end-diastolic volume index, 143 +/- 43 mL/m(2)) and function (mean RV ejection fraction [EF], 48 +/- 10%) on MRI. End-diastolic volume was underestimated on 3DE by 20% (P < .001) and to a greater degree in larger ventricles (P < .001). There was no significant difference in EF measurements between 3DE methods and MRI except for ABD (-2.6 +/- 6, P = .03). The mean analysis time for ABD was 5 minutes, compared with 19 minutes for manual tracing (P < .0001). CONCLUSION: Approximately half the patients with CHD had adequate three-dimensional echocardiographic images. Three-dimensional echocardiography accurately estimated EF but underestimated volume, particularly when the right ventricle was dilated. ABD minimally underestimated EF but offered a significant reduction in analysis time.