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)

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

Lysosomal glycogen storage disease without acid maltase deficiency is characterized by the triad of clinical manifestations (hypertrophic cardiomyopathy), mental retardation, and mild myopathy), morphologic findings (glycogen storage, glycogenosomes, and autophagic vacuoles), and normal glycolytic enzyme activities. Though most of the patients suffering from the triad were males, family studies often revealed female patients with only cardiomyopathy. So far 27 cases have been reported. The cardiac involvement is progressive and fatal and as severe in females as in males. Many patients of both sexes die in their youth, unexpectedly, because of cardiac failure. The specific biochemical defect causing this disease remains unknown. From abnormal lectin staining patterns on the membrane and preclinical morphologic changes in biopsied skeletal muscle, membranous abnormality is suspected in this disease.
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PMID:[Lysosomal glycogen storage disease without acid maltase deficiency]. 857 57

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

We describe a boy with an early lethal hypertrophic vacuolar cardiomyopathy of neonatal onset. Abnormal intra- and extralysosomal glycogen storage disease was demonstrated in heart and skeletal muscles. Glycogen content was twice the normal in muscles and over 3-fold the normal in the heart. In this organ, over 50% of the intracellular space was occupied by glycogen and possibly oligosaccharides, as demonstrated by the quantitative morphometric analysis of electron micrographs. The activity of acid alpha-glucosidase was increased in the heart, skeletal muscles, and liver, but was normal in leukocytes. A review of the 11 previously published pedigrees of lysosomal glycogen storage disease with normal in vitro alpha-glucosidase activity allows the delineation of three clinical entities: juvenile and neonatal pseudo-Pompe diseases and partial Pompe disease. Partial Pompe disease, due to the tissue-specific absence of acid alpha-glucosidase, was observed in a single patient. The most common form is the late-onset pseudo-Pompe disease, which is characterized by severe cardiomyopathy and mild myopathy appearing in the second or third decade, prominent arrhythmia with Wolf-Parkinson-White syndrome, and sometimes mental retardation. Patients reported as suffering from Antopol disease probably belong to this group. Dominant inheritance (autosomal or X linked) is likely in most families. The present report appears to be the first one to describe a rapidly fatal neonatal form of lysosomal glycogenosis without acid maltase deficiency. The mode of inheritance of this form is not known. Differential diagosis includes Pompe disease (similar histology) and cardiac phosphorylase b kinase deficiency (similar clinical course). The delineation of neonatal pseudo-Pompe disease makes enzymatic confirmation mandatory in each case suspected of Pompe disease.
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PMID:Nosology of lysosomal glycogen storage diseases without in vitro acid maltase deficiency. Delineation of a neonatal form. 938 33

Phosphoglycerate kinase (PGK) catalyses the transfer of the acylphosphate group of 1,3-diphosphoglycerate to ADP with formation of 3-phosphoglycerate and ATP in the terminal stage of the glycolytic pathway. Two young brothers are presented who both experienced muscle pain, cramps and stiffness shortly after beginning heavy exercise. After these episodes they noticed that the urine was dark brown, indicating rhabdomyolysis and myoglobinuria. The neurological examinations were without remarks. There was no lactate increase in the ischaemic forearm exercise test. Both had very low PGK levels in muscle, erythrocytes, leukocytes and fibroblasts. This is the first family with more than one affected case of PGK deficiency and exercise-induced stiffness, myalgia and rhabdomyolysis. The clinical manifestations may resemble myophosphorylase deficiency (McArdle's disease: glycogenosis Type V) and muscle phosphofructokinase deficiency (Tarui's disease: glycogenosis Type VII). PGK deficiency is inherited as an X-linked trait and may show other features such as mental retardation and/or haemolytic anaemia.
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PMID:Phosphoglycerate kinase deficiency in two brothers with McArdle-like clinical symptoms. 1080 25

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

"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

India, like other developing countries, is facing an accelerating demographic switch to non-communicable diseases. In the cities congenital malformations and genetic disorders are important causes of morbidity and mortality. Due to the high birth rate in India a very large number of infants with genetic disorders are born every year almost half a million with malformations and 21,000 with Down syndrome. In a multi-centric study on the causes of referral for genetic counselling the top four disorders were repeated abortions (12.4%), identifiable syndromes (12.1%), chromosomal disorders (11.3%) and mental retardation (11%). In a more recent study in a private hospital the top reasons for referral were reproductive genetics (38.9%)--comprising prenatal diagnosis, recurrent abortions, infertility and Torch infections--mental retardation +/- multiple congenital anomalies (16.1%), Down syndrome (9.1%), thalassemia/haemophilia (8.8%), and muscle dystrophy/spinal muscular atrophy (8.4%). The disorders for which prenatal has been done over an 18-month-period are given. A recent study carried out in three centers (Mumbai, Delhi and Baroda) on 94,610 newborns by using a uniform proforma showed a malformation frequency of 2.03%, the commonest malformations are neural tube defects and musculo-skeletal disorders. The frequency of Down syndrome among 94,610 births was 0.87 per 1000, or 1 per 1150. Screening of 112,269 newborns for aminoacid disorders showed four disorders to be the commonest--tyrosinemia, maple syrup urine disease and phenylketonuria. Screening of cases of mental retardation for aminoacid disorders revealed four to be the commonest--hyperglycinemia, homocystinuria, alkaptonuria, and maple syrup urine disease. Metabolic studies of cases of mental retardation in AIIMS, Delhi and KEM Hospital, Mumbai, demonstrated that common disorders were those of mucopolysaccharides, lysosomes, Wilson disease, glycogen storage disease and galactosemia. It is estimated that beta- thalassemia has a frequency at birth of 1:2700, which means that about 9,000 cases of thalassemia major are born every year. Almost 5200 infants with sickle cell disease are born every year. Disorders, which deserve to be screened in the newborn period, are hypothyroidism and G-6-PD deficiency, while screening for aminoacid and other metabolic disorders could presently be restricted to symptomatic infants.
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PMID:Burden of genetic disorders in India. 1126 88

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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