Clinical outcome and phenotypic expression in LAMP2 cardiomyopathy.
Clinical outcome and phenotypic expression in LAMP2 cardiomyopathy.
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DOI：
10.1001/jama.2009.371
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发表时间：
2009-03-25
影响因子：
120.7
通讯作者：
Seidman, Christine E.
中科院分区：
文献类型：
--
作者：
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.
X连锁溶酶体相关膜蛋白基因（LAMP 2; Danon病）突变在年轻患者中产生心肌病，临床上类似于肌节蛋白突变引起的肥厚型心肌病（HCM）。然而，这种新认识的疾病的自然史和表型表达是不完全解决，它的鉴定可能具有重要的临床意义。确定LAMP 2心肌病的临床后果以及诊断和管理策略的有效性。在我们实验室从诊断时间（7-17岁;中位数14）至2008年10月之前确定的7名年轻LAMP 2患者（6名男性）中前瞻性评估临床病程和结局。这种疾病的表型表达进行了评估，临床和尸检。植入式心脏起搏器、心脏活性药物和心脏移植。进行性心力衰竭/心源性死亡和移植。在7.3 ± 3（SD）年的随访中，在12至24岁时，研究患者发生LV收缩功能障碍（射血分数25 ± 7[SD]%）和腔扩大，以及特别不良的临床后果，包括：进行性难治性心力衰竭和死亡（n = 4）、猝死（n = 1）、心脏骤停（n = 1）或心脏移植（n = 1）。LV肥大特别明显（最大室间隔，29-65 mm;平均值44±15[SD]），包括2例患者，年龄分别为23岁和15岁，厚度分别为60 mm和65 mm。在6例患者中，在进入研究时，心室预激模式与最大R波或S波（40-145 mm;平均74± 38 mm）的电压显著增加和深度倒置T波相关。尸检结果包括与储存病一致的组织病理学特征的组合（即，空泡化的肌细胞簇），但也是由于肌节蛋白突变引起的典型HCM（即，肌细胞紊乱、小血管疾病、心肌瘢痕形成）。LAMP 2心肌病是一种严重的疾病过程，其特征在于快速临床恶化，导致< 25岁的年轻患者的心源性死亡。这些观察结果强调了及时的分子诊断对预测预后和早期考虑心脏移植的重要性。
Mutations in X-linked lysosome-associated membrane protein gene (LAMP2; Danon disease) produce a cardiomyopathy in young patients that clinically mimics 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 of LAMP2 cardiomyopathy and the efficacy of diagnostic and management strategies. Clinical course and outcome were assessed prospectively in 7 young LAMP2 patients (6 males) previously identified in our laboratory from the time of diagnosis (ages 7–17; median 14) to October 2008. Phenotypic expression of this disease was assessed both clinically and at autopsy. Implantable defibrillators, cardioactive medications, and heart transplantation. Progressive heart failure/cardiac death, and transplant. Over 7.3 ± 3 (SD) years of follow-up, and by 12 to 24 years of age, the study patients developed LV systolic dysfunction (ejection fraction 25 ± 7[SD]%) 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). LV hypertrophy was particularly marked (maximum ventricular septum, 29–65 mm; mean 44±15[SD]) including 2 patients with massive thickness of 60 mm and 65 mm at ages 23 and 15 years, respectively. In 6 patients, at study entry a ventricular pre-excitation pattern was associated with markedly increased voltages for maximum R- or S-wave (40–145 mm; mean 74±38mm), and deeply inverted T-waves. Autopsy findings included a combination of histopathologic features consistent with a storage disease (i.e., clusters of vacuolated myocytes), but also typical of HCM due to sarcomere protein mutations (i.e., myocyte disarray, small vessel disease, myocardial scarring). LAMP2 cardiomyopathy is a profound disease process characterized by rapid clinical deterioration leading 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.
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影响因子：
2.8
作者：
Varnava, AM;Elliott, PM;McKenna, WJ
通讯作者：
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影响因子：
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作者：
Harris, Kevin M.;Spirito, Paolo;Maron, Barry J.
通讯作者：
Maron, Barry J.
影响因子：
37.8
作者：
MARON, BJ;ROBERTS, WC
通讯作者：
ROBERTS, WC
影响因子：
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作者：
Van Driest, SL;Ackerman, MJ;Gersh, BJ
通讯作者：
Gersh, BJ
DOI：
10.1016/s0735-1097(03)00855-6
发表时间：
2003-09-03
影响因子：
24
作者：
Maron, BJ;Casey, SA;Aeppli, DM
通讯作者：
Aeppli, DM