Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q00604 (X-linked)
 16,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lysosomal glycogen storage disease with normal acid maltase (Danon) is caused by primary lysosome-associated membrane protein-2 (LAMP-2) deficiency. Typically, the disease begins after the first decade; however, two infantile patients had similar histologic features. The infantile disorder is distinct from Danon disease, because, in both infants, LAMP-2 protein is present in skeletal muscle. Deposition of C5b-9 and multilayered basal lamina in one patient suggest that the infantile disease is pathogenically similar to X-linked myopathy with excessive autophagy.
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PMID:Infantile autophagic vacuolar myopathy is distinct from Danon disease. 1155 28

Primary lysosome-associated membrane protein-2 (LAMP-2) deficiency is an X-linked disease, characterized by the clinical triad of cardiomyopathy, vacuolar myopathy and mental retardation, previously known as Danon disease. Mutations of lamp-2 gene have been reported so far in about 20 patients, one of whom was Italian. We describe a new Italian case with persistent hyperCKemia, exercise intolerance and hypertrophic cardiomyopathy but with no muscle weakness or mental impairment. Muscle biopsy revealed a vacuolar myopathy with mild glycogen storage, and immunohistochemical studies detected LAMP-2 deficiency. A new nucleotide substitution (T961C) on exon 8 of lamp-2 gene was identified as responsible for the protein deficiency. This is the first missense mutation so far described. LAMP-2 deficiency should be considered as a cause of recurrent hyperCKemia and hypertrophic cardiomyopathy.
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PMID:Asymptomatic hyperCKemia in a case of Danon disease due to a missense mutation in Lamp-2 gene. 1590 87

Danon disease, an X-linked cardioskeletal myopathy caused by primary deficiency of lysosome-associated membrane protein-2 (LAMP-2), is clinically characterized by cardiomyopathy, myopathy, and variable mental retardation. The pathological hallmark of the disease is the absence of LAMP-2 immunohistochemical staining in muscle. The LAMP-2 gene mutations reported thus far are generally private mutations. We describe two cases of Danon disease with different clinical presentation, in whom we identified the same exon skipping mutation c.928G>A in the LAMP-2 gene. The first patient was affected by an early onset myopathy and hypertrophic cardiomyopathy (HCM) that partially improved with drug treatment. A first muscle biopsy at age 4 months showed markedly increased glycogen, and acid maltase deficiency was ruled out biochemically. A second muscle biopsy, performed at age 3(1/2) years, showed very mild abnormalities. The second child at age 15 years had mild, diffuse muscle weakness and wasting, moderate mental deficiency, and HCM. Two serial biopsies performed at age 8 and 15 years showed similar findings of multiple esterase-positive vacuoles in type I myofibers. In both patients the immunohistochemical study demonstrated the absence of LAMP-2 in skeletal muscle.
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PMID:Phenotypic heterogeneity in two unrelated Danon patients associated with the same LAMP-2 gene mutation. 1621 5

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

We report a 46-year-old male patient with late-onset vacuolar myopathy and dilated cardiomyopathy. Acid maltase activity of the muscle was normal, but the biopsied muscle specimen stained for lysosome-associated membrane protein-2 (LAMP-2), which has recently been reported to be deficient in muscles of patients with Danon disease. The clinical features of the patient are distinct from X-linked myopathy with excessive autophagy, infantile autophagic vacuolar myopathy and autophagic vacuolar myopathy with late-onset and multiorgan involvement (Kaneda).
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PMID:LAMP-2 positive vacuolar myopathy with dilated cardiomyopathy. 1754 Dec 30

Danon disease, a rare glycogen storage disease, is a dominant X-linked disorder. It is due to mutation in gene for lysosome-associated membrane protein 2 (LAMP 2). The LAMP 2 gene is located on Xq24, and its mutation causes primary deficiency of LAMP 2 and myocyte hypertrophy by accumulations of vacuoles containing glycogen. Danon disease is clinically characterized by the triad of hypertrophic cardiomyopathy (HCM), proximal myopathy and mental retardation. Myopathy and mental retardation can be absent, and cardiomyopathy is usually hypertrophic. This is a case report of the patient with genetically confirmed Danon disease and mixed cardiomyopathy, but without myopathy and mental retardation. ECG showed typical Wolff-Parkinson-White (WPW) pattern while echocardiography demonstrated hypertrophy and dilatation of all cardiac chambers with impaired systolic and diastolic function. Male sex, early onset of symptoms, massive hypertrophy of the myocardium and ventricular preexcitation indicate a genetic basis for HCM. Therapeutic measures, except heart transplantation, do not improve prognosis substantially. Only an accurate diagnosis in patients with unexplained HCM helps in establishing of the appropriate treatment strategies and adequate genetic consultation.
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PMID:[Danon disease: a case report and literature overview]. 1764 61

We report a 46-year-old male patient with late-onset vacuolar myopathy and dilated cardiomyopathy. Acid maltase activity of the muscle was normal, but the biopsied muscle specimen stained for lysosome-associated membrane protein-2 (LAMP-2), which has recently been reported to be deficient in muscles of patients with Danon disease. The clinical features of the patient are distinct from X-linked myopathy with excessive autophagy, infantile autophagic vacuolar myopathy and autophagic vacuolar myopathy with late-onset and multiorgan involvement (Kaneda).
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PMID:A novel vacuolar myopathy with dilated cardiomyopathy. 1787 13

Danon disease, an extremely rare X-linked dominant disorder, is characterized clinically by hypertrophic cardiomyopathy (HCM), skeletal myopathy, and variable degree of mental retardation with autophagic vacuoles in skeletal and cardiac muscle. Reportedly, Danon disease is caused by a primary deficiency of a major lysosomal membrane glycoprotein, LAMP2 (lysosome-associated membrane protein 2). Here we review the clinical features, molecular genetics, related animal model, and differential diagnosis of Danon disease.
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PMID:Danon disease as a cause of autophagic vacuolar myopathy. 1837 32

Danon disease is an X-linked cardioskeletal myopathy, originally reported as "lysosomal glycogen storage disease with normal acid maltase," resulting from a primary deficiency of lysosome-associated membrane protein-2 because of mutations in the lysosome-associated membrane protein-2 gene. Classic clinical features in males include cardiomyopathy (100%, eventually), myopathy (90%), and mental retardation (70%), but mostly of a mild degree. We report on an unusual presentation in a patient with autism, motor delay, and a normal cardiac evaluation. The presence of multiorgan involvement, including elevated liver enzymes, abnormal cranial magnetic resonance imaging, and diffuse hypotonia with swallowing difficulties, prompted a muscle biopsy. A quadriceps muscle biopsy was performed, and the findings were most suspicious for a glycogen storage-type disease. Subsequently, a pathogenic lysosome-associated membrane protein-2 mutation was found. To our knowledge, there are no previous clinical reports of autism in children with Danon disease.
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PMID:Danon disease: an unusual presentation of autism. 1855 74

Danon disease is an X-linked dominant multisystem disorder that includes hypertrophic cardiomyopathy with skeletal myopathy, and results from mutations in the gene encoding the lysosome-associated membrane protein-2 (LAMP-2). To date, over 20 different mutations in LAMP2 have been identified. Three members of a family, a male proband (18 years old) and 2 sisters (15 and 20 years old) were studied. Their mother had been diagnosed with dilated cardiomyopathy at the age of 39 years, and died from advanced heart failure at the age of 43 years. The proband developed marked concentric hypertrophy at the age of 5 years and DNA analyses revealed a novel hemizygous frameshift mutation (c.573delA) in exon 5. The 2 affected sisters were also heterozygous for the same mutation. Functional analyses of this novel LAMP2 mutation are mandatory.
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PMID:Novel LAMP-2 mutation in a family with Danon disease presenting with hypertrophic cardiomyopathy. 1905 86


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