Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026827 (hypotonia)
 5,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

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

Glycogen storage disease type IV (GSD-IV) is a rare autosomal recessive disease caused by a deficiency of glycogen branching enzyme (GBE) activity. This results in the accumulation of abnormal glycogen in the liver and other organs. We report the case of a 14-month-old female patient with typical hepatic pathologic findings of GSD-IV. The patient suffered from decreased muscle tone and progressive hepatosplenomegaly since birth. A wedge biopsy of the liver showed enlarged hepatocytes with colorless to faintly eosinophilic ground glass intracytoplasmic inclusions. Portal fibrosis and lobular, fibrous septa were present. Ultrastructure of the inclusions revealed non-membrane-bound fibrillar material 5 nm in maximal diameter. Enzyme study revealed a total deficiency of GBE activity.
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PMID:Glycogen storage disease type IV: a case report. 1053 7

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 storage disease type IV (GSD-IV) is an autosomal recessive genetic disorder due to a deficiency in the activity of the glycogen branching enzyme (GBE). A deficiency in GBE activity results in the accumulation of glycogen with fewer branching points and long, unbranched outer chains. The disorder results in a variable phenotype, including musculoskeletal, cardiac, neurological, and hepatic involvement, alone or in continuum, which can be identified at any stage of life. The classic form of GSD-IV is a hepatic presentation, which presents in the first 18 months of life with failure to thrive, hepatomegaly, and cirrhosis that progresses to liver failure, resulting in death by age 5 years. A severe congenital musculoskeletal phenotype with death in the neonatal period has also been described. We report an unusual case of congenital musculoskeletal presentation of GSD-IV with stable congenital hypotonia, gross motor delay, and severe fibro-fatty replacement of the musculature, but no hepatic or cardiac involvement. Molecular analysis revealed two novel missense mutations with amino acid changes in the GBE gene (Q236H and R262C), which may account for the mild phenotype.
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PMID:Non-lethal congenital hypotonia due to glycogen storage disease type IV. 1652 37

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

Glycogen storage disease type IV (GSD IV, or Andersen disease) is an autosomal recessive disorder due to the deficiency of 1,4-alpha-glucan branching enzyme (or glycogen branching enzyme, GBE1), resulting in an accumulation of amylopectin-like polysaccharide in muscle, liver, heart and central and peripheral nervous system. Typically, the presentation is in childhood with liver involvement up to cirrhosis. The neuromuscular form varies in onset (congenital, perinatal, juvenile and adult) and in severity. Congenital cases are rare, and fewer than 20 cases have been described and genetically determined so far. This form is characterized by polyhydramnios, neonatal hypotonia, and neuronal involvement; hepatopathy is uncommon, and the babies usually die between 4 weeks and 4 months of age. We report the case of an infant who presented severe hypotonia, dilatative cardiomyopathy, mild hepatopathy, and brain lateral ventricle haemorrhage, features consistent with the congenital form of GSD IV. He died at one month of life of cardiorespiratory failure. Muscle biopsy and heart and liver autoptic specimens showed many vacuoles filled with PAS-positive diastase-resistant materials. Electron-microscopic analysis showed mainly polyglucosan accumulations in all the tissues examined. Postmortem examination showed the presence of vacuolated neurons containing this abnormal polysaccharide. GBE1 biochemical activity was virtually absent in muscle and fibroblasts, and totally lacking in liver and heart as well as glycogen synthase activity. GBE1 gene sequence analysis revealed a novel homozygous nonsense mutation, p.E152X, in exon 4, correlating with the lack of enzyme activity and with the severe neonatal involvement. Our findings contribute to increasing the spectrum of mutation associated with congenital GSD IV.
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PMID:Neuropathological study of skeletal muscle, heart, liver, and brain in a neonatal form of glycogen storage disease type IV associated with a new mutation in GBE1 gene. 1935 89

The fatal infantile neuromuscular presentation of branching enzyme deficiency (glycogen storage disease type IV) due to mutations in the gene encoding the glycogen branching enzyme, is a rare but probably underdiagnosed cause of congenital hypotonia. We report an infant girl with severe generalized hypotonia, born at 33 weeks gestation who required ventilatory assistance since birth. She had bilateral ptosis, mild knee and foot contractures and echocardiographic evidence of cardiomyopathy. A muscle biopsy at 1 month of age showed typical polyglucosan storage. The autopsy at 3.5 months of age showed frontal cortex polymicrogyria and polyglucosan bodies in neurons of basal ganglia, thalamus, substantia innominata, brain stem, and myenteric plexus, as well as liver involvement. Glycogen branching enzyme activity in muscle was virtually undetectable. Sequencing of the GBE1 gene revealed a homozygous 28 base pair deletion and a single base insertion at the same site in exon 5. This case confirms previous observations that GBE deficiency ought to be included in the differential diagnosis of congenital hypotonia and that the phenotype correlates with the 'molecular severity' of the mutation.
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PMID:Branching enzyme deficiency/glycogenosis storage disease type IV presenting as a severe congenital hypotonia: muscle biopsy and autopsy findings, biochemical and molecular genetic studies. 2083 45

Anderson disease, also known as glycogen storage disease type IV (MIM 232500), is a rare autosomal recessive disorder caused by a deficiency of glycogen branching enzyme. Glycogen storage disease type IV has a broad clinical spectrum ranging from a perinatal lethal form to a nonprogressive later-onset disease in adults. Here, we report 2 unrelated infants who were born small for their gestational age and who had profound hypotonia at birth and thus needed mechanical ventilation. Both of these patients shared the same frameshift mutation (c.288delA, pGly97GlufsX46) in the GBE1 gene. In addition, both of these patients were found to have 2 different large deletions in the GBE1 gene; exon 7 and exons 2 to 7, respectively, on the other alleles. This case report also highlights the need for a more comprehensive search for large deletion mutations associated with glycogen storage disease type IV, especially if routine GBE1 gene sequencing results are equivocal.
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PMID:Association of the congenital neuromuscular form of glycogen storage disease type IV with a large deletion and recurrent frameshift mutation. 2191 43


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