Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.4.1.18 (branching enzyme)
 628 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a late onset form of polysaccharide myopathy with progressive limb girdle muscles weakness, without cardiomyopathy. Muscle biopsy showed a vacuolar myopathy in type 1 fibres. The PAS positive diastase resistant deposits were made of filamentous material at electron microscopy similar to long chain glycogen. Muscle glycogen levels and glycogen metabolism enzymes were normal. Numerous abnormal mitochondrial with paracrystalline inclusions were observed around the storage material. Twelve patients with polysaccharide amylopectin-like storage myopathy have previously been reported. This disease must be distinguished from other diseases with polysaccharide accumulation such as branching enzyme deficiency and some cases of phosphofructokinase deficiency. In other disorders, no deficient enzymes in the glycogen pathway was found. Some of them show systemic storage (Lafora disease, adult polyglucosan body disease). Corpora amylacea, Bielchowsky bodies and basophilic degeneration of the myocardium represent localised depositions. A few inclusions can also be observed in hypothyroid myopathy. In polysaccharide myopathy allosteric inactivation of phosphofructokinase by a mitochondrial dysfunction is considered by analogy with cases of polysaccharide storage related to phosphofructokinase deficiency.
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PMID:[Polysaccharide amylopectin-type storage myopathy]. 130 60

A first Japanese case of an adult polysaccharide storage myopathy (APSM) was reported. A 30-year-old Japanese male was admitted because of weakness of the lower limbs. The onset of the symptoms was at the age of 23. Neurologically he had moderate weakness of proximal limb muscles involving the lower limbs more than the upper and slightly decreased vibratory sense in the feet. His gait was waddling. The following laboratory values were obtained; SGOT 45 I.U., SGPT 83 I.U., CPK 218 I.U., UA 8.3 mg/dl. Ischemic exercise test of the forearm showed a normal rise of venous lactate. EMG revealed a mixture of myopathic and mild neurogenic patterns characterized by motor units of short duration and low amplitude with intermittent high amplitude potentials, fibrillation and fasciculation. There were also prominent myotonic discharges without clinical myotonia. MCV was normal, however sural nerve SCV was slightly slow (lt. 36/m, rt. 38 m/s). Muscle biopsy revealed vacuolar myopathy. Most vacuoles contained basophilic, PAS-positive, diastase-resistant and Lugol's iodine-negative material. With ATPase staining there was type 1 fiber predominance (84%), but the vacuoles were predominantly seen in type 2A fiber. In ultrastructural study, the storage material was located under the sarcolemma and in the areas of the intermyofibrillar network. No delimiting membranes were seen. At higher magnification, these masses were consisted of filaments. Therefore the storage material was considered to be unusual polysaccharide. Glycogen storage disease was suspected, however, biochemical study of the muscle specimen disclosed no enzymatic defect including branching enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Adult polysaccharide storage myopathy]. 269 Nov 65

A 7 1/2-year-old girl had exercise intolerance and exertional dyspnea. Four months later, congestive heart failure developed, with recurrent chylous pleural effusions, and she died at age 8 1/2 years. Endomyocardial biopsy tissue showed abundant PAS-positive, diastase-resistant cytoplasmic deposits. Similar inclusions were seen in muscle, skin, and liver specimens. Postmortem studies showed that the abnormal polysaccharide was especially abundant in heart and muscle, but was also present in all other tissues, including the central nervous system. Glycogen isolated from heart, muscle, and spinal cord showed a shift of the iodine spectrum toward higher than normal wavelengths. Branching enzyme activity was lacking in the muscle biopsy specimen and in all postmortem tissues; glycogenolytic enzymes had normal activities. These studies show that cardiomyopathy can be the first symptom of generalized branching enzyme deficiency and that the degree of accumulation of the abnormal polysaccharide may vary in different tissues.
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PMID:Severe cardiopathy in branching enzyme deficiency. 347 93

In type IV glycogen storage disease, the abnormal storage material is a partially amylase-resistant, PAS-positive polysaccharide and a deficiency of the branching enzyme is present in virtually all cases studied so far. Electron microscopic, biochemical and enzymatic studies were carried out in a child presenting with the clinical and histological features of this disease. Electron microscopic study showed the amylase-resistant material to be fibrillar and poorly soluble in buffers. Iodine spectrum analysis indicated that the lambda max of the liver polysaccharide was between that of normal glycogen and that of typical type IV glycogen. Branching enzyme activity was not detectable in the patient's leucocytes but was close to normal in the liver and clearly detectable in cultured fibroblasts. These results suggest that the absolute value of the deficiency of the branching enzyme in the liver of patients with type IV glycogen storage disease could be questioned. Alternatively this patient as well as another one reported in the literature could be considered as subtypes of the disease in whom liver and fibroblast branching enzyme activity remains detectable in vitro.
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PMID:[A study of the abnormal polysaccharide in a child with type IV glycogen storage disease (author's transl)]. 694 1

A neonate with deficiency of branching enzyme (glycogenosis type IV) presented symptoms of severe hypotonia pre- and postnatally, and dilated cardiomyopathy in early infancy. The classical clinical manifestation of liver cirrhosis was not present, although amylopectin-like inclusions were found in the hepatocytes. In contrast to a previous report, the neurons in the brain stem and spinal anterior horns contained PAS-positive, diastase-resistant deposits. The combined involvement of the muscles and motor neurones could account for the severity of hypotonia. The muscle biopsy, electromyogram and biochemical and enzyme assays were helpful in establishing the diagnosis.
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PMID:Neonatal hypotonia and cardiomyopathy secondary to type IV glycogenosis. 805 7

A baby girl was born hypotonic and was respirator-dependent until death at 43 days of age. A muscle biopsy revealed PAS-positive, diastase-resistant sarcoplasmic inclusions with a vaguely fibrillar structure by electron microscopy. Biochemical studies at autopsy disclosed complete absence of branching enzyme in skeletal muscle and heart, and a deficiency of phosphorylase activity in skeletal muscle with a modest reduction in myocardium. Storage material was present in glia and perikarya of neurons, increasing in amount in the rostrocaudal direction, involving most severely the motor neurons in the brain stem and spinal cord, dorsal root ganglia and myenteric plexi. Inclusions were also present in most organs, especially liver and skeletal muscle. Ultrastructurally, the inclusions ranged from granular aggregates of membrane-bound material concentrated in the region of Golgi apparatus to large filamentous bodies similar to polyglucosan bodies. This baby differs from other patients with infantile glycogenosis IV by the severity and onset of symptoms at birth, involvement of neuronal perikarya and widespread extraneural deposits. The combined deficiencies of branching enzyme and phosphorylase may have accounted for the unique clinical and neuropathological findings.
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PMID:Concomitant branching enzyme and phosphorylase deficiencies. An unusual glycogenosis with extensive neuronal polyglucosan storage. 817 7

Type IV glycogenosis or Andersen disease is characterized by a deficiency in branching enzyme. This rare disease is exceptionally seen at birth. The clinico-pathological data are then typical: severe hypotonia with hypoventilation and cellular storage, without any hepatosplenomegaly. The stored material is PAS positive, sometimes made of crystals and appeared birefringent under polarized light. Granulo-filamentous inclusions are shown by electron microscopy, essentially observed in muscle and liver without cirrhosis. Death occurs rapidly. The present case was typical. It is the eleventh reported case in the literature.
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PMID:[Congenital variant of type IV glycogenosis. Anatomoclinical report of a case]. 909 Sep 36

Glycogenosis type IV is an autosomal recessive disease, exceptionally diagnosed at birth: only very few reports of the fatal perinatal neuromuscular form have been described. We report on two sibling male newborns who died at 10 and 4 weeks of age with clinical signs of a systemic storage disease. Prenatal history included polyhydramnios, reduced fetal movements and fetal hydrops, and Caesarean section was performed at 36 weeks of gestational age because of fetal distress. At birth, both babies showed severe hypotonia, hyporeflexia and no spontaneous breathing activity. They never showed active movements, sucking and swallowing and were respirator-dependent until death. A muscle biopsy revealed, in both patients, the presence of PAS-positive and partially diastase-resistant cytoplasmic inclusions containing granular and filamentous amylopectin-like material. This suggested that the stored material consisted of abnormal glycogen. At autopsy, ultrastructural examination of cardiac and skeletal muscle, liver, kidney and brain showed PAS-positive diastase-resistant eosinophilic cytoplasmic inclusions. Determination of branching enzyme activity, in cultured fibroblasts from the second patient, showed markedly reduced enzyme activity, confirming diagnosis of glycogenosis type IV. Our patients showed the full spectrum of both prenatal signs (hydrops, polyhydramnios) and postnatal signs (hypotonia, hyporeflexia, absence of active movements, cardiomegaly), which have been reported previously. They suffered from a very severe form of glycogenosis type IV with clinical and histological involvement of many tissues and organs. Diagnosis was accomplished on the second baby and required several biochemical and histological studies, in order to rule out both neuromuscular disorders and the most common storage diseases with neonatal onset. In our experience, the correct interpretation of the histological findings was essential in the search for the diagnosis.
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PMID:Severe neonatal onset of glycogenosis type IV: clinical and laboratory findings leading to diagnosis in two siblings. 1566 76

Glycogen branching enzyme deficiency (glycogen storage disease type IV, GSD-IV) is a rare autosomal recessive disorder of the glycogen synthesis with high mortality. Two female newborns showed severe hypotonia at birth and both died of cardiorespiratory failure, at 4 and 12 weeks, respectively. In both patients, muscle biopsies showed deposits of PAS-positive diastase-resistant material and biochemical analysis in cultured fibroblasts showed markedly reduced glycogen branching enzyme activity. Direct sequencing of GBE1 gene revealed that patient 1 was homozygous for a novel c.691+5 g>c in intron 5 (IVS5+5 g>c). RT-PCR analysis of GBE1 transcripts from fibroblasts cDNA showed that this mutation produce aberrant splicing. Patient 2 was homozygous for a novel c.1643G>A mutation leading to a stop at codon 548 in exon 13 (p.W548X). These data underscore that in GSD-IV a severe phenotype correlates with null mutations, and indicate that RNA analysis is necessary to characterize functional consequences of intronic mutations.
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PMID:Null mutations and lethal congenital form of glycogen storage disease type IV. 1766 46

A diagnosis of GSD-IV was established in three premature, floppy infants based on characteristic, however unusually pleomorphic polyglucosan bodies at the electron microscopic level, glycogen branching enzyme deficiency in two cases, and the identification of GBE1 mutations in two cases. Pleomorphic polyglucosan bodies in muscle fibers and macrophages, and less severe in Schwann cells and microglial cells were noted. Most of the inclusions were granular and membrane-bound; others had an irregular contour, were more electron dense and were not membrane bound, or homogenous ('hyaline'). A paracrystalline pattern of granules was repeatedly noted showing a periodicity of about 10 nm with an angle of about 60 degrees or 120 degrees at sites of changing linear orientation. Malteser crosses were noted under polarized light in the larger inclusions. Some inclusions were PAS positive and others were not. Severely atrophic muscle fibers without inclusions, but with depletion of myofibrils in the plane of section studied indicated the devastating myopathic nature of the disease. Schwann cells and peripheral axons were less severely affected as was the spinal cord. Two novel protein-truncating mutations (c.1077insT, p.V359fsX16; g.101517_127067del25550insCAGTACTAA, DelExon4-7) were identified in these families. The present findings extend previous studies indicating that truncating GBE1 mutations cause a spectrum of severe diseases ranging from generalized intrauterine hydrops to fatal perinatal hypotonia and fatal cardiomyopathy in the first months of life.
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PMID:Congenital type IV glycogenosis: the spectrum of pleomorphic polyglucosan bodies in muscle, nerve, and spinal cord with two novel mutations in the GBE1 gene. 1866 Nov 38


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