CLINICAL OUTCOME AND PHENOTYPIC EXPRESSION IN LAMP2 CARDIOMYOPATHY
| Autor: | Maron, Barry J., Roberts, William C., Arad, Michael, Haas, Tammy S., Spirito, Paolo, Wright, Gregory B., Almquist, Adrian K., Baffa, Jeanne M., Saul, J. Philip, Ho, Carolyn Y., Seidman, Jonathan, Seidman, Christine E. |
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| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Heart Failure
Male Sarcomeres Adolescent Lysosome-Associated Membrane Glycoproteins Cardiomyopathy Hypertrophic Article Glycogen Storage Disease Type IIb Electrocardiography Young Adult Death Sudden Cardiac Phenotype Echocardiography Lysosomal-Associated Membrane Protein 2 Mutation Disease Progression Heart Transplantation Humans Female Hypertrophy Left Ventricular Autopsy Child Follow-Up Studies |
| Popis: | Mutations in X-linked lysosome-associated membrane protein gene (LAMP2; Danon disease) produce a cardiomyopathy in young patients that clinically mimics severe hypertrophic cardiomyopathy (HCM) due to sarcomere protein mutations. However, the natural history and phenotypic expression of this newly recognized disease is incompletely resolved and its identification may have important clinical implications.To determine the clinical consequences, outcome, and phenotypic expression of LAMP2 cardiomyopathy associated with diagnostic and management strategies.Clinical course and outcome were assessed prospectively in 7 young patients (6 boys) with defined LAMP2 mutations from the time of diagnosis (age 7-17 years; median, 14 years) to October 2008. Phenotypic expression of this disease was assessed both clinically and at autopsy.Progressive heart failure, cardiac death, and transplant.Over a mean (SD) follow-up of 8.6 (2.6) years, and by age 14 to 24 years, the study patients developed left ventricular systolic dysfunction (mean [SD] ejection fraction, 25% [7%]) and cavity enlargement, as well as particularly adverse clinical consequences, including progressive refractory heart failure and death (n = 4), sudden death (n = 1), aborted cardiac arrest (n = 1), or heart transplantation (n = 1). Left ventricular hypertrophy was particularly marked (maximum thickness, 29-65 mm; mean [SD], 44 [15] mm), including 2 patients with massive ventricular septal thickness of 60 mm and 65 mm at ages 23 and 14 years, respectively. In 6 patients, a ventricular pre-excitation pattern at study entry was associated with markedly increased voltages of R-wave or S-wave (15-145 mm; mean [SD], 69 [39] mm), and deeply inverted T-waves. Autopsy findings included a combination of histopathologic features that were consistent with a lysosomal storage disease (ie, clusters of vacuolated myocytes) but also typical of HCM due to sarcomere protein mutations (ie, myocyte disarray, small vessel disease, myocardial scarring).LAMP2 cardiomyopathy is a profound disease process characterized by progressive clinical deterioration leading rapidly to cardiac death in young patients (25 years). These observations underscore the importance of timely molecular diagnosis for predicting prognosis and early consideration of heart transplantation. |
| Databáze: | OpenAIRE |
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