Familial X-linked cardiomyopathy (Danon disease): diagnostic confirmation by mutation analysis of the LAMP2gene

Balmer, Christian; Ballhausen, Diana; Bosshard, Nils U.; Steinmann, Beat; Boltshauser, Eugen; Bauersfeld, Urs; Superti‐Furga, Andrea

doi:10.1007/s00431-005-1678-z

Cited by 44 publications

(42 citation statements)

References 24 publications

(30 reference statements)

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“…Maron et al 9 reported that six of seven Danon disease patients were boys with a median age of 14 years, and six patients were with WPW syndrome and deeply inverted T-waves at diagnosis. Furthermore, all the three patients had markedly elevated serum hepatic enzymes and CK concentrations, consistent with previous studies by Yang et al, 7 Maron et al, 9 Cottinet et al, 10 Balmer et al, 11 and Morisawa et al…”

Section: Discussionsupporting

confidence: 80%

Danon disease as a cause of concentric left ventricular hypertrophy in patients who underwent endomyocardial biopsy

Cheng¹,

Cui

Tian³

et al. 2011

European Heart Journal

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Section: Discussionsupporting

confidence: 80%

Danon disease as a cause of concentric left ventricular hypertrophy in patients who underwent endomyocardial biopsy

Cheng¹,

Cui

Tian³

et al. 2011

European Heart Journal

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“…The clinical features, including hypertrophic cardiomyopathy, skeletal myopathy and developmental delay, were of various degree between the affected individuals, in spite of the same LAMP-2 mutation. This observation highlights that, in this context of heterogeneous presentation with generally private mutations (Balmer et al 2005;Maron et al 2009;Sugie et al 2002), morphological and immunohistochemistry examination of muscle biopsy can provide key elements for orienting the etiologic investigations and must be recommended.…”

Section: Discussionmentioning

confidence: 95%

Danon disease: intrafamilial phenotypic variability related to a novel LAMP‐2 mutation

Cottinet

Bergemer-Fouquet

Toutain

et al. 2010

J of Inher Metab Disea

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Danon disease is an X-linked lysosomal disorder, characterized by hypertrophic cardiomyopathy, skeletal myopathy and mental retardation. We report a family with a novel mutation, in which the mother and her three sons were affected with various clinical presentations. A massive hypertrophy of the left ventricle was the predominant feature in the three male patients, with different degrees of severity of cardiac symptoms, from isolated palpitations to cardiac failure and sudden death. Muscle pain and weakness were also variable, but constantly associated with increased plasma CK levels. Finally, the male patients had variable degree of a mental retardation. The mother had an attenuated phenotype, limited to a mild hypertrophic cardiomyopathy with premature ventricular contractions diagnosed during her 40's. Microscopy examination of skeletal muscle biopsy, performed in the youngest patient, demonstrated atrophic myofibers with intracytoplasmic vacuoles suggesting lysosomal glycogen storage disease. Immunohistochemistry analyses in muscle specimen showed no detectable Lysosomal-Associated Membrane Protein-2 (LAMP-2), in keeping with the diagnosis of Danon disease. However, a very low expression of a shortened LAMP-2 protein could be evidenced by Western-blot in the patient's fibroblasts. Molecular investigations identified a novel splicing mutation (IVS6 + 1delG) in the LAMP-2 gene. This case report highlights the intrafamilial variability of Danon disease phenotype. In this case, morphological examination of muscle biopsy, showing lysosomal storage myopathy, and immunohistochemistry analyses can provide key elements for orienting etiologic investigations.

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“…LAMP2 deficiency, also referred to as Danon disease, is a lysosomal storage disease with normal acid maltase, and X-linked vacuolar cardiomyopathy and mental retardation [12]. Clinical and pathological signs, as well as the genetics (mutation of Lamp-2 gene only present in Danon disease), differ for these two disorders and even though TEM could confirm for both the presence of similar ultrastructural abnormalities as disrupted lysosomes, deleterious effect on the myofibrillar contents, and exocitosis, the accurate ultrastructural observation of autophagic vacuoles, it is important in distinguishing Danon disease from AMD [17][18][19][20][21]. In fact, only in Danon disease do some of these autophagic vacuoles have basal lamina on the luminal side, which probably indicates a sarcolemmal origin [19].…”

Section: Discussionmentioning

confidence: 97%

The Role of Ultrastructural Examination in Storage Diseases

Papa

Tarantino

Preda

et al. 2010

Ultrastructural Pathology

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Storage diseases (SDs) are rare metabolic disorders characterized by the intra- or extralysosomal accumulation of unmetabolized compounds. Different causes determine the buildup of undigested material, resulting in typical histochemical and ultrastructural changes. Ultrastructural examination of tissue from patients with clinically suspected SDs may disclose pathognomonic alterations or suggest a differential diagnosis even in the absence of clinically evident involvement of the biopsied tissue. Accurate diagnosis of SDs requires a continuous integration of clinical, biochemical, ultrastructural, and, when available, molecular data. It is also important for the pathologist to be familiar with the morphological variability characterizing each SD, because some morphologies are often the early stages of undeveloped forms and morphologically similar diseases are easily confused. The major advantages of transmission electron microscopy (TEM) techniques are discussed, emphasizing the current role of TEM as a rapid, cost-effective, and efficient diagnostic tool.

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Familial X-linked cardiomyopathy (Danon disease): diagnostic confirmation by mutation analysis of the LAMP2gene

Abstract: Early diagnosis of Danon disease is important for genetic counselling and timely cardiac transplantation, the only effective therapeutic option.

Cited by 44 publications

References 24 publications

Danon disease as a cause of concentric left ventricular hypertrophy in patients who underwent endomyocardial biopsy

Danon disease as a cause of concentric left ventricular hypertrophy in patients who underwent endomyocardial biopsy

Danon disease: intrafamilial phenotypic variability related to a novel LAMP‐2 mutation

The Role of Ultrastructural Examination in Storage Diseases

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