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)

Muscle biopsies from three patients with cardiomyopathy, mental retardation and increased serum creatine kinase levels revealed scattered fibers with tiny intracytoplasmic vacuoles containing basophilic and acid phosphatase-positive material and slightly increased amounts of PAS-positive granules. These findings are consistent with those seen in the so-called lysosomal glycogen storage disease with normal acid maltase. In addition to the vacuoles, there were occasional folds or indentations in the sarcolemma which were connected to the membrane enclosing the vacuoles. These membranes were well demonstrated histochemically by the nonspecific esterase and acetylcholinesterase stains. On electron microscopy, most of the vacuoles were bounded by membranes with basal lamina. The vacuolar membrane stained positively with antibodies raised to dystrophin, dystrophin-associated glycoproteins, laminin and type 4 collagen, and it was identical to the sarcolemma and its basal lamina. Therefore, the membrane abnormality which causes sarcolemmal folding is probably critical to understanding the pathomechanism of this disease.
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PMID:Sarcolemmal indentation in cardiomyopathy with mental retardation and vacuolar myopathy. 753 16

A family is reported in which three members were affected by cardiomyopathy. Two members died unexpectedly in their second decade. Only a 23-year-old male suffered from the triad of clinical manifestations (cardiomyopathy, mental retardation and vacuolar myopathy). Morphologic findings and biochemical studies of his biopsied skeletal muscle and cultured fibroblasts confirmed lysosomal glycogen storage disease with normal acid maltase that was first described by Danon et al. In this study we demonstrated early morphologic changes, storage of glycogen and abnormal membranous structures in disorganized myofibers in biopsied skeletal muscle from the elder sister, who only showed cardiomyopathy clinically. The aggregation of autophagosomes was prominent in cultured fibroblasts, with an increased glycogen content. The activity of acid alpha-glucosidase was higher than normal. This is a systemic storage disease with different expression in males and females.
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PMID:Morphologic findings in biopsied skeletal muscle and cultured fibroblasts from a female patient with Danon's disease (lysosomal glycogen storage disease without acid maltase deficiency). 769 92

The clinical and morphological findings of a familial case affected by mental retardation, severe biventricular hypertrophic cardiomyopathy and vacuolar myopathy are reported. The phenotype of this patient is similar to that described by other authors, in which a lysosomal glycogen storage disease with normal acid maltase levels was suspected. However, in our case the vacuoles were stained by several antibodies directed against various sarcolemmal proteins, such as dystrophin and spectrin, and therefore, were not of lysosomal origin. Some of these vacuoles were clearly derived from the splitting of the fibres and invagination of the extracellular space; autophagic vacuoles were not observed. The accumulation of desmin-type, intermediate filaments was demonstrated on immunocytochemistry both in the skeletal and cardiac muscles. A brother of the propositus was also affected by mental retardation, severe cardiomyopathy and died suddenly at the age of 24 yr. A cardiomyopathy and mental subnormality were also present in other male cousins of the proband, while sudden death occurred in several females relatives, whose intelligence was normal. None of these latter individuals was available for further investigation. This report expands the spectrum of desmin associated myopathy and cardiomyopathy to include a familial condition with associated mental retardation.
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PMID:Familial cardiomyopathy, mental retardation and myopathy associated with desmin-type intermediate filaments. 791 71

Lysosomal glycogen storage in muscle with normal acid maltase activity is a rare inherited condition characterized by cardiomyopathy, mental retardation and mild myopathy in males, but generally only cardiomyopathy in females. Three cases (index case, his sister and her son) are described in a family with at least two other affected members. The index case underwent a successful heart transplant. The sister has cardiac involvement, myopathic changes and mental impairment--to our knowledge the first report of multisystem involvement in a female. We propose that skeletal muscle should be examined in young patients with hypertrophic cardiomyopathy. Furthermore, female relatives of males with the disease should be investigated for cardiomyopathy; they would be excellent candidates for life-saving heart transplant, since myopathy and mental retardation, if clinically evident, are mild.
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PMID:Lysosomal glycogen storage with normal acid maltase: a familial study with successful heart transplant. 791 72

Glycogen storage disease with normal acid maltase first reported by Danon et al. was characterized clinically by mental retardation, cardiomyopathy, and proximal myopathy. Since the first report, 17 patients have been reported including 5 patients from Japan. In this paper we described a 26-year-old man who had dilatated cardiomyopathy with a pacemaker implanted at age 22 years. He was admitted to our hospital complaining of easy fatigability in February 1992. Neurological findings showed that he had mental retardation. Serum CK, GOT, GPT and aldolase levels were elevated. Histopathological study of biopsied skeletal muscle showed intracytoplasmic vacuoles with increased acid phosphatase and slightly increased PAS positive material. Electron microscopic study revealed numerous glycogenosomes (autophagic vacuoles containing glycogen). These pathological findings were similar to acid maltase deficiency, but activities of carbohydrate metabolic enzyme including acid maltase activity were normal in the biopsied muscle. From these results, he was diagnosed as having glycogen storage disease with normal acid maltase. We also found abnormal platelet function and glycogen accumulation in the platelets, which have not been previously described. The disease is probably a systemic disorder affecting not only skeletal and cardiac muscles, but platelets.
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PMID:[A case of glycogen storage disease with normal acid maltase accompanied with the abnormal platelet function]. 799 92

A 13-year-old boy with mental retardation developed idiopathic cardiomyopathy and glycogen storage myopathy, but with normal lysosomal enzyme activities, consistent with a syndrome of lysosomal glycogen storage disease with normal acid maltase coined by Danon et al (1981). He was in good health except for WPW syndrome diagnosed at 7 years of age. He had heart murmur with abnormal ECG, elevated serum GOT, GPT, LDH, CK and aldolase levels. An echocardiogram showed obstructive hypertrophic cardiomyopathy. Lysosomal enzyme activities including acid alpha-glucosidase in fibroblasts were within normal limits. In the biopsied biceps brachii muscle, there was a mild variation in fiber size. An approximately 10 percent of myofibers had tiny vacuoles which contained periodic acid Schiff positive granules and were slightly high in acid phosphatase activity. The vacuoles were encircled by membranes with high neuron specific enolase (NSE) and acethylcholin-esterase (AchE) activities. On electron microscopy, numerous autophagic vacuoles scavenging glycogen granules were recognized as seen in acid maltase deficiency. Because the vacuolar membranes were high in NSE and AchE activities, lysosomal membrane formation from the cell membrane may be defective. When one has a patient with mild to moderate mental retardation, idiopathic hypertrophic cardiomyopathy and high serum CK level, muscle biopsy must be performed to rule out the present disorder.
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PMID:[A patient with lysosomal glycogen storage disease with normal acid maltase]. 839 37

A 14-year-old boy with mild mental retardation, myopathy, and nonobstructive hypertrophic cardiomyopathy (HCM) with clinical and histopathologic features consistent with lysosomal glycogen storage disease with normal acid maltase is described. The case illustrates the aggressive nature of the cardiomyopathy of this syndrome. This condition is associated with malignant ventricular arrhythmias, relentlessly progressive ventricular dilatation, dysfunction, and sudden death. It is important to recognize this unusual and malignant form of HCM to precipitate low early diagnosis by muscle biopsy. Patients with this condition would be excellent candidates for life-saving heart transplant as the myopathy and mental retardation are mild and nonprogressive. The underlying biochemical defect and mode of inheritance of this syndrome are unclear. However, a significant proportion are genetically related and thus, relatives may benefit from family screening.
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PMID:Case report: lysosomal glycogen storage disease with normal acid maltase: an unusual form of hypertrophic cardiomyopathy with rapidly progressive heart failure. 885 67

A 26-year-old male with cardiomyopathy, cervical muscle weakness and mental retardation was diagnosed as having glycogen storage disease with normal acid maltase on the basis of his clinical, pathological and biochemical findings. Positron emission tomography showed that cerebral oxygen metabolism was normal, while cerebral glucose metabolism was decreased in the cerebral cortexes. The decrease of the glucose metabolic rate may reflect an abnormality of cerebral glucose metabolism in this disorder and may be related to mental retardation, which is one of the characteristic symptoms.
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PMID:Cerebral oxygen and glucose metabolism in glycogen storage disease with normal acid maltase: case report. 886 26

A 29-year-old male who had a past history of mild ECG abnormality of arrhythmia at the age of 14 years, was referred to our hospital because of elevated serum creatine kinase (CK) level. He had never been aware of muscular weakness nor cardiac symptoms. Neurological examination revealed normal muscle strength of all extremities except marked back muscle weakness. He had normal intelligence. On laboratory examination, serum AST, ALT, LDH, aldolase, CK and myoglobin levels were elevated. Both lactate and pyruvate levels were normally responded after an ischemic exercises test. Acid maltase activity was normal in white blood cells. A muscle biopsy obtained from rectus femoris muscle revealed vacuolar myopathy with mildly increased PAS positive material. On electron microscopy, there were autophagic vacuoles scavenging glycogen particles and cytoplasmic debris, and sarcolemmal indentation, compatible with the findings of lysosomal glycogen storage disease with normal acid maltase. This patient had unusual clinical features of absent mental retardation and no apparent cardiomyopathy. Accordingly, mental retardation is probably not necessary to see later onset of cardiac muscle involvement.
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PMID:[Lysosomal glycogen storage disease with normal acid maltase (Danon) without apparent cardiomyopathy and mental retardation]. 1088 38

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


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