Glycogen Storage Diseases and Cardiomyopathy
http://www.100md.com
《新英格兰医药杂志》
To the Editor: Arad et al. (Jan. 27 issue)1 report that LAMP2 mutations (Danon's disease) are an important cause of hypertrophic cardiomyopathy. That one of their patients had an "adolescent response to cardiac disease," however, strangely misses the point that mental retardation commonly accompanies this disease. Both of the patients in the original cases described by Danon et al.2 had mental retardation, and in a series of 38 patients, described by Sugie et al.,3 70 percent of male patients (14 of 20) and 6 percent of female patients (1 of 18) had mental retardation. Lobrinus et al.4 and Sugie et al.5 have also reported that patients with Danon's disease did not reach other neurodevelopmental milestones — most with this disease did not walk until they were 18 months old and many had learning difficulties.
We recommend that patients who present with hypertrophic cardiomyopathy be asked about their educational performance. If there is a history of learning difficulties, they should be referred for further evaluation. If a diagnosis of Danon's disease is made, all first-degree relatives should be offered genetic testing and stratification of the risk of sudden death from cardiac causes.
Jonathan C.P. Roos, M.A.
Timothy M. Cox, M.D.
University of Cambridge
Cambridge CB2 2QQ, United Kingdom
References
Arad M, Maron BJ, Gorham JM, et al. Glycogen storage diseases presenting as hypertrophic cardiomyopathy. N Engl J Med 2005;352:362-372.
Danon MJ, Oh SJ, DiMauro S, et al. Lysosomal glycogen storage disease with normal acid maltase. Neurology 1981;31:51-57.
Sugie K, Yamamoto A, Murayama K, et al. Clinicopathological features of genetically confirmed Danon disease. Neurology 2002;58:1773-1778.
Lobrinus JA, Schorderet DF, Payot M, et al. Morphological, clinical and genetic aspects in a family with a novel LAMP-2 gene mutation (Danon disease). Neuromuscul Disord 2005;15:293-298.
Sugie K, Koori T, Yamamoto A, et al. Characterization of Danon disease in a male patient and his affected mother. Neuromuscul Disord 2003;13:708-711.
The authors reply: Roos and Cox "recommend that patients who present with hypertrophic cardiomyopathy be asked about their educational performance." We concur. However, our article goes further, suggesting that other clinical findings, such as preexcitation on the electrocardiogram or elevated levels of creatine kinase, should also trigger evaluation of LAMP2 and PRKAG2 genes. The central theme of our article is that whereas many LAMP2 mutations cause Danon's disease, with its associated neurologic and muscular abnormalities, some LAMP2 mutations produce primary cardiac disease that mimics hypertrophic cardiomyopathy without neuromuscular or behavioral abnormalities. Only two of the six patients in our study had even mild behavioral or psychological abnormalities — relatively common problems among adolescents with cardiac disease.1 If these patients had been cared for according to standard cardiologic practice,2 which does not include genetic testing,3 the cause of their cardiomyopathy would not have been identified.
Michael Arad, M.D.
Sheba Medical Center
Tel Hashomer 52662, Israel
Barry J. Maron, M.D.
Minneapolis Heart Institute Foundation
Minneapolis, MN 55407
J.G. Seidman, Ph.D.
Harvard Medical School
Boston, MA 02115
seidman@genetics.med.harvard.edu
References
Wray J, Long T, Radley-Smith R, Yacoub M. Returning to school after heart or heart-lung transplantation: how well do children adjust? Transplantation 2001;72:100-106.
Maron BJ, McKenna WJ, Danielson GK, et al. American College of Cardiology/European Society of Cardiology clinical expert consensus document on hypertrophic cardiomyopathy: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents and the European Society of Cardiology Committee for Practice Guidelines. J Am Coll Cardiol 2003;42:1687-1713.
Maron BJ, Seidman JG, Seidman CE. Proposal for contemporary screening strategies in families with hypertrophic cardiomyopathy. J Am Coll Cardiol 2004;44:2125-2132.
We recommend that patients who present with hypertrophic cardiomyopathy be asked about their educational performance. If there is a history of learning difficulties, they should be referred for further evaluation. If a diagnosis of Danon's disease is made, all first-degree relatives should be offered genetic testing and stratification of the risk of sudden death from cardiac causes.
Jonathan C.P. Roos, M.A.
Timothy M. Cox, M.D.
University of Cambridge
Cambridge CB2 2QQ, United Kingdom
References
Arad M, Maron BJ, Gorham JM, et al. Glycogen storage diseases presenting as hypertrophic cardiomyopathy. N Engl J Med 2005;352:362-372.
Danon MJ, Oh SJ, DiMauro S, et al. Lysosomal glycogen storage disease with normal acid maltase. Neurology 1981;31:51-57.
Sugie K, Yamamoto A, Murayama K, et al. Clinicopathological features of genetically confirmed Danon disease. Neurology 2002;58:1773-1778.
Lobrinus JA, Schorderet DF, Payot M, et al. Morphological, clinical and genetic aspects in a family with a novel LAMP-2 gene mutation (Danon disease). Neuromuscul Disord 2005;15:293-298.
Sugie K, Koori T, Yamamoto A, et al. Characterization of Danon disease in a male patient and his affected mother. Neuromuscul Disord 2003;13:708-711.
The authors reply: Roos and Cox "recommend that patients who present with hypertrophic cardiomyopathy be asked about their educational performance." We concur. However, our article goes further, suggesting that other clinical findings, such as preexcitation on the electrocardiogram or elevated levels of creatine kinase, should also trigger evaluation of LAMP2 and PRKAG2 genes. The central theme of our article is that whereas many LAMP2 mutations cause Danon's disease, with its associated neurologic and muscular abnormalities, some LAMP2 mutations produce primary cardiac disease that mimics hypertrophic cardiomyopathy without neuromuscular or behavioral abnormalities. Only two of the six patients in our study had even mild behavioral or psychological abnormalities — relatively common problems among adolescents with cardiac disease.1 If these patients had been cared for according to standard cardiologic practice,2 which does not include genetic testing,3 the cause of their cardiomyopathy would not have been identified.
Michael Arad, M.D.
Sheba Medical Center
Tel Hashomer 52662, Israel
Barry J. Maron, M.D.
Minneapolis Heart Institute Foundation
Minneapolis, MN 55407
J.G. Seidman, Ph.D.
Harvard Medical School
Boston, MA 02115
seidman@genetics.med.harvard.edu
References
Wray J, Long T, Radley-Smith R, Yacoub M. Returning to school after heart or heart-lung transplantation: how well do children adjust? Transplantation 2001;72:100-106.
Maron BJ, McKenna WJ, Danielson GK, et al. American College of Cardiology/European Society of Cardiology clinical expert consensus document on hypertrophic cardiomyopathy: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents and the European Society of Cardiology Committee for Practice Guidelines. J Am Coll Cardiol 2003;42:1687-1713.
Maron BJ, Seidman JG, Seidman CE. Proposal for contemporary screening strategies in families with hypertrophic cardiomyopathy. J Am Coll Cardiol 2004;44:2125-2132.