Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Four boys, aged 2 years 5 months to 3 years 7 months, with large hepatomegaly due to phosphorylase-kinase deficiency glycogenosis, were given a trial of sodium dextrothyroxine (D-T4) at a mean dose of 0.165 mg/kg/day for an average period of 6 months. Phosphorylase-kinase was undetectable in the haemolysates of erythrocytes (3 patients) or in the liver (one patient) before, and still undetectable in the haemolysates of the four patients during treatment, thus pointing to X-linked phosphorylase-kinase deficiency glycogen storage disease (GSD IXb). D-T4 administration resulted in complete normalization of liver size, decrease of serum GOT (p less than 0.02), GPT (p less than 0.05) and triglycerides (p less than 0.01) to normal values, as well as correction of mild asymptomatic hypoglycemia (p less than 0.01). As long as the outcome of type IXb glycogenosis in adult life remains undefined, dextrothyroxine therapy seems an effective means of reducing liver size and correcting part of the biochemical abnormalities of the disease.
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PMID:Dextrothyroxine treatment of phosphorylase-kinase deficiency glycogenosis in four boys. 28 May 44

We report a 5-year-old boy with lysosomal glycogen storage disease and normal acid maltase activity. This patient, the fourth reported in the literature, was referred to our hospital for evaluation of elevated serum GOT, GPT, and CK activities. He had neither muscle weakness nor atrophy. Echocardiography demonstrated marked thickening of the intraventricular septum and left ventricular wall which indicated hypertrophic cardiomyopathy. Biopsied skeletal muscle disclosed massive accumulation of glycogen and autophagic vacuoles. Electron microscopy of biopsied cardiac muscle revealed severe myofibrillar disruption with marked accumulation of free and intralysosomal glycogen. Activities of all major glycolytic enzymes in skeletal muscle, including acid maltase, were normal. It is unknown why muscle lysosomes appeared to be unable to digest the trapped glycogen despite the presence of acid maltase. Our findings illustrate the importance of performing skeletal muscle investigation during childhood in patients with hypertrophic cardiomyopathy.
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PMID:Glycogen storage disease with normal acid maltase: skeletal and cardiac muscles. 249 94

Serum muscle enzyme activity assays were routinely performed in 36 patients with glycogen storage diseases (15 types 1a and 1b, 12 type III, and 9 types VI and IX). Creatine phosphokinase serum activity was increased only in type III. Glutamate-pyruvate transaminase, aldolase and lactate dehydrogenase serum activities were increased in all the forms of glycogen storage disease studied. Muscle involvement may at least partly explain the increased serum enzyme activities in type III.
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PMID:[Determination of blood level of muscle enzymes in glycogenoses with liver involvement: a diagnostic criterion]. 274 13

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 19-year-old man, who could run only slowly since childhood and who walked on his toes since 12 years of age, noted difficulty in climbing upstairs at 17 years of age. He was admitted to Kyushu University Hospital because of elevated AST, ALT and CK levels. On admission, the liver was palpable two fingerbreadths beneath the right costal margin. A neurological examination revealed a low IQ on WAIS-R, a decreased muscle tonus in his four limbs, moderate weakness of the neck flexor and bilateral tibialis anterior muscles, contracture of the ankle joints, and bilateral pes cavus. The serum CK was elevated to 1,124U/l. Hepatic enzymes, such as AST, ALT, LDH and gamma-GTP were also moderately increased in the sera. A needle EMG disclosed myogenic patterns in the limb muscles. Biopsied biceps brachii muscle showed a mild variation in the fiber size and multiple tiny vacuoles in 5-10% of the muscle fibers. PAS and acid phosphatase were strongly positive in some vacuoles. On electron microscopy, numerous autophagic vacuoles containing glycogen granules were observed. The acid maltase activities were, however, normal in the peripheral blood lymphocytes, the biopsied muscle, and the cultured skin fibroblasts. He was thus diagnosed to have lysosomal glycogen storage disease with normal acid maltase. A histological examination of the biopsied liver revealed the portal and central veins to be slightly sclerotic. In addition, mild fatty changes and frequent nuclear vacuolization were present in the hepatocytes. On electron microscopy, enlarged mitochondria with irregular cristae were also observed. Due to the fact that the cardiac function was well preserved, these hepatic lesions were thought to result from the metabolic abnormalities underlying in this disorder.
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PMID:[Hepatic involvement in a case of lysosomal glycogen storage disease with normal acid maltase]. 1054 8

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 acid lipase (LAL) deficiency results in Wolman disease and cholesteryl ester storage disease (CESD), a more benign form. CESD is a recessive disorder characterized by hypercholesterolaemia, hypertriglyceridaemia, low blood HDL and variable phenotype, while hepatomegaly is usually evident during childhood or adolescence. An 11-year-old girl was referred to our department for combined hyperlipidaemia (total cholesterol 323, triglycerides 259 mg/dl). All family members had normal lipid profile and liver function tests. At 8 years she was admitted for acute Epstein-Barr virus infection, with hepatosplenomegaly and elevation of liver enzymes. Liver-spleen enlargement resolved, but serum alanine aminotransferase and aspartate aminotransferase were persistently twice the upper limits, with other liver function tests within the normal range. Ultrasonography showed normal liver and spleen size and minimal hepatic steatosis. Infectious, autoimmune and metabolic causes of elevated liver enzymes were ruled out, including glycogen storage disease. Dysbetalipoproteinaemia was also ruled out (ApoE phenotype: E3E3). In the following 2 years the girl was symptom-free, BMI was at the 50th-75th centile for age and lipid profile was unchanged despite a low-fat diet. At 13 years of age, low acid lipase activity was demonstrated in leukocytes (10 nmol/h/ per mg protein, normal 140-380) and cultured skin fibroblasts (181 nmol/h per mg protein, normal 1100-2400), leading to diagnosis of CESD. CESD usually progresses to hepatic fibrosis, with high risk of premature atherosclerosis. CESD prevalence may be underestimated in the general population. The diagnosis may be considered in all subjects with atypical combined hyperlipidaemia (usually dominant in transmission or related to metabolic syndrome) and atypical 'fatty liver disease', in the absence of overweight.
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PMID:Combined hyperlipidaemia as a presenting sign of cholesteryl ester storage disease. 1921 73

A rare case of glycogen storage disease type III with unusually absent ketone body production during hypoglycemia is presented. A 10-month-old boy presented with asymptomatic hepatomegaly. GOT/GPT 2555/1160 IU/L, CK 302 IU/L, triglycerides 1223 mg/dL, cholesterol 702 mg/dL and uric acid 7.9 mg/dL. After a 9-hour fast, glucose was 27 mg/dL and adequate lipolysis without ketogenesis was observed (total/free carnitine 34.5/20 micromol/L, free fatty acids 1620 micromol/L and beta-hydroxybutyrate 172 micromol/L). Result of MCT (medium-chain triglycerides) load test: basal hydroxybutyrate 29 micromol/L rose to 5748 micromol/L. Treatment with a fat-restricted diet supplemented with formula containing MCT was initiated and the patient presented a satisfactory initial evolution. Three months later, CK were 3000 IU/L. Muscle biopsy was diagnostic of glycogenosis. Enzymatic activity in skin fibroblasts was 0% for amylo-1,6-glucosidase. The diagnosis of glycogenosis type III was established. Echocardiography performed at that time showed non-obstructive ventricular hypertrophy. Until now hypoketosis during hypoglycemia has only been described in glycogenosis type I.
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PMID:Glycogen storage disease type III with hypoketosis. 2107 27

Glycogen storage disease type IIIa (GSD IIIa) is an autosomal recessive disease caused by deficiency of glycogen debranching enzyme (GDE) in liver and muscle. The disorder is clinically heterogeneous and progressive, and there is no effective treatment. Previously, a naturally occurring dog model for this condition was identified in curly-coated retrievers (CCR). The affected dogs carry a frame-shift mutation in the GDE gene and have no detectable GDE activity in liver and muscle. We characterized in detail the disease expression and progression in eight dogs from age 2 to 16 months. Monthly blood biochemistry revealed elevated and gradually increasing serum alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) activities; serum creatine phosphokinase (CPK) activity exceeded normal range after 12 months. Analysis of tissue biopsy specimens at 4, 12 and 16 months revealed abnormally high glycogen contents in liver and muscle of all dogs. Fasting liver glycogen content increased from 4 months to 12 months, but dropped at 16 months possibly caused by extended fibrosis; muscle glycogen content continually increased with age. Light microscopy revealed significant glycogen accumulation in hepatocytes at all ages. Liver histology showed progressive, age-related fibrosis. In muscle, scattered cytoplasmic glycogen deposits were present in most cells at 4 months, but large, lake-like accumulation developed by 12 and 16 months. Disruption of the contractile apparatus and fraying of myofibrils was observed in muscle at 12 and 16 months by electron microscopy. In conclusion, the CCR dogs are an accurate model of GSD IIIa that will improve our understanding of the disease progression and allow opportunities to investigate treatment interventions.
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PMID:Characterization of a canine model of glycogen storage disease type IIIa. 2273 56


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