Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

"Lysosomal glycogen storage disease with normal acid maltase" which was originally described by Danon et al., is characterized clinically by cardiomyopathy, myopathy and variable mental retardation. The pathological hallmark of the disease is intracytoplasmic vacuoles containing autophagic material and glycogen in skeletal and cardiac muscle cells. Sarcolemmal proteins and basal lamina are associated with the vacuolar membranes. Here we report ten unrelated patients, including one of the patients from the original case report, who have primary deficiencies of LAMP-2, a principal lysosomal membrane protein. From these results and the finding that LAMP-2-deficient mice manifest a similar vacuolar cardioskeletal myopathy, we conclude that primary LAMP-2 deficiency is the cause of Danon disease. To our knowledge this is the first example of human cardiopathy-myopathy that is caused by mutations in a lysosomal structural protein rather than an enzymatic protein.
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PMID:Primary LAMP-2 deficiency causes X-linked vacuolar cardiomyopathy and myopathy (Danon disease). 1097 94

Danon disease ('lysosomal glycogen storage disease with normal acid maltase') is characterized by a cardiomyopathy, myopathy and variable mental retardation. Mutations in the coding sequence of the lysosomal-associated membrane protein 2 (LAMP-2) were shown to cause a LAMP-2 deficiency in patients with Danon disease. LAMP-2 deficient mice manifest a similar vacuolar cardioskeletal myopathy. In addition to the patient reports LAMP-2 deficiency in mice causes pancreatic, hepatocytic, endothelial and leucocyte vacuolation. LAMP-2 deficient mice represent a valuable animal model of Danon disease. They will further be used to study the exact role of LAMP-2 in autophagy and to analyse the consequences of an impaired autophagic pathway in various tissues.
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PMID:Disease model: LAMP-2 enlightens Danon disease. 1142 88

Herein, we report a new case of Danon's disease in a 41-year-old Frenchman. This patient displays the typical clinical triad, with cardiomyopathy, mental retardation and myopathy, and a vacuolar myopathy without acid alpha-glucosidase deficiency. He has also developed a diffuse chorio-capillary ocular atrophy, and represents the second case of successful heart transplantation in this lysosomal disease. Interestingly, analysis of LAMP-2 protein expression in cultured fibroblasts revealed a primary deficiency of this lysosomal membrane protein. This defect resulted from a yet undescribed deletion in exon 7 of lamp-2 gene.
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PMID:Danon's disease (X-linked vacuolar cardiomyopathy and myopathy): a case with a novel Lamp-2 gene mutation. 1239 43

Lysosome-associated membrane protein-2 deficiency (LAMP-2 deficiency), or Danon disease, is a rare X-linked lysosomal disease characterized by cardiomyopathy, vacuolar myopathy, and mental retardation. Less than 20 families with mutations of the Lamp-2 gene have been reported. We describe a family from Sardinia with eight affected patients (4 females and 4 males) and a novel mutation in exon 2 of the Lamp-2 gene (c.102_103delAG). Females developed isolated cardiomyopathy in adulthood, whereas males presented with cardiomyopathy, myopathy, and mental retardation before the age of 20 years. Cardiomyopathy was lethal in three females in their 40s and in three males before the age 20 years. One patient was successfully treated by heart transplantation with more than 5-year follow-up. This study demonstrates that Danon disease is a frequently fatal condition that is potentially treatable with heart transplantation.
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PMID:Novel Lamp-2 gene mutation and successful treatment with heart transplantation in a large family with Danon disease. 1637 18

Danon disease, an X-linked dominant disorder, results from mutations in the lysosome-associated membrane protein-2 (LAMP2) gene and presents with hypertrophic cardiomyopathy, skeletal myopathy, and mental retardation. To investigate the effects of LAMP2 gene mutations on protein expression in different tissues, we screened LAMP2 gene mutations and LAMP-2 protein deficiency in the skeletal muscle of nine unrelated patients with hypertrophic cardiomyopathy and vacuolar myopathy. We identified three novel families (including one affected mother) with unreported LAMP2 gene null mutations and LAMP-2 protein deficiency in skeletal and myocardial muscle, leukocytes, and fibroblasts. LAMP-2 protein deficiency was detectable in various tissues, including leukocytes, explaining the multisystem clinical involvement. Skeletal muscle immunopathology showed that mutant protein was not localized in the Golgi complex, vacuolar membranes expressed sarcolemmal-specific proteins, and the degree of muscle fiber vacuolization correlated with clinical muscle involvement. In our female patient, muscle histopathology and LAMP-2 protein analysis was inconclusive, indicating that diagnosis in females requires mutation identification. The random X-chromosome inactivation found in muscle and leukocytes excluded the possibility that selective involvement of some tissues in females is due to skewed X-chromosome inactivation. Therefore, biochemical analysis of leukocytes might be used for screening in male patients, but genetic screening is required in females.
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PMID:Generalized lysosome-associated membrane protein-2 defect explains multisystem clinical involvement and allows leukocyte diagnostic screening in Danon disease. 1656 4

Danon disease is a rare X-linked dominant disorder caused by lysosomal-associated membrane protein 2 (LAMP2) deficiency and is characterized by hypertrophic cardiomyopathy, cardiac conduction abnormalities, skeletal vacuolar myopathy, variable degree of mental retardation, and peripheral pigmentary retinopathy. We describe a novel splice mutation in the LAMP2 gene in a French Canadian family. By identifying this novel mutation we were able to offer genetic screening and counseling to all family members. Presymptomatic diagnosis is important as cardiac surveillance can be life-saving.
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PMID:Danon disease due to a novel splice mutation in the LAMP2 gene. 1800 70

We describe a case of a 30-year-old man with Danon's disease, an X-linked genetic disorder due to deficiency of lysosomal-associated membrane protein 2 with secondary intracytoplasmatic glycogen and autophagic material storage. This disease is characterized by skeletal muscle involvement, mental retardation, ophthalmic abnormalities, and cardiac disease. In this patient, cardiac involvement was characterized by hypertrophic cardiomyopathy in young age, preexcitation, and parossistic atrioventricular block. The patient underwent to an implantable cardioverter defibrillator implantation for conduction disorders and for primary prevention of sudden death, a frequent event in Danon's disease. This case report describes cardiac involvement with conduction disorders and multiple pacemaker malfunctions in Danon's disease.
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PMID:Pacemaker malfunctions in Danon's disease. 1818 22

We report a case of a 16-yr-old male with Danon disease caused by a novel mutation in the LAMP-2 gene. Mutations in the LAMP-2 gene result in the absence of LAMP-2 on immunohistochemical staining of muscle tissue, thus defining Danon disease, a rare X-linked myopathy. It is characterized clinically by HCM or left ventricular hypertrophy, a WPW pattern on ECG, variable degrees of muscular weakness (skeletal myopathy), mental retardation, and retinal changes. The patient presented with severe skeletal muscular weakness and respiratory failure. He also had a history of two OHTs, the first one for severe HCM and the second for allograft rejection. The patient's myopathy was initially presumed to be exclusively related to steroid-induced "critical care myopathy." However, further evaluation with a thigh muscle biopsy revealed autophagic vacuoles with sarcolemnal features suggestive of a lysosomal storage disorder. DNA analysis ultimately identified a previously unreported hemizygous IVS6+3_+6delGAGT splice site deletion mutation in the LAMP-2 gene located within the 5' splice site of intron 6, consistent with Danon disease.
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PMID:Danon disease with typical early-onset cardiomyopathy in a male: focus on a novel LAMP-2 mutation. 1828 7

Danon disease is an X-linked disorder resulting from mutations in the lysosome-associated membrane protein-2 (LAMP2) gene. We report a male patient with skeletal myopathy, mental retardation, and massive hypertrophic obstructive cardiomyopathy necessitating heart transplantation. Immunohistochemistry of skeletal muscle and leukocytes, western blot analysis of leukocytes and cardiac muscle, flow cytometry, and DNA sequencing were performed. Muscle biopsy revealed autophagic vacuolar myopathy and lack of immunohistochemically detectable LAMP-2. Diagnosis of Danon disease was confirmed by western blot analysis of myocardial tissue and peripheral blood sample of the patient showing deficiency of LAMP-2 in myocardium and leukocytes. Moreover, absence of LAMP-2 in lymphocytes, monocytes and granulocytes was shown by flow cytometric analysis. Genetic analysis of the LAMP2 gene revealed a novel 1-bp deletion at position 179 (c.179delC) at the 3' end of exon 2, resulting in a frameshift with a premature stop codon.
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PMID:Danon disease: case report and detection of new mutation. 1958 70

Danon disease is a rare lysosomal disorder. It is due to deficiency of lysosomal-associated protein-2. In human LAMP-2 gene is located at chromosome region Xq24. Danon disease is characterized by hypertrophic cardiomyopathy, skeletal myopathy, mental retardation and retinopathy. To date, the morphological characterization of Danon disease has been limited to endomyocardial and skeletal muscle biopsies. In the current study we demonstrated that electron microscopy of a more accessible tissue, skin biopsies, is a useful method in the diagnosis of Danon disease.
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PMID:Electron microscopic findings in skin biopsies from patients with Danon disease. 2107 Jan 64


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