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)

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

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 III (GSD III) was found in the past with an unusual frequency among North African Jews in Israel. The aim of this study was to review the long-term clinical course of GSD III's patients in Israel. Relevant pediatric and adult clinical units of all Israeli hospitals were approached to report on their GSD III patients. 21 (14 M/7F) live patients were located. The average age of the patients was nearly twenty years. Eleven patients were older than 18 years of age. 76% of the patients were of Jewish North African origin, 14% of Jewish European origin, and 10% were Arab Muslims. The symptoms at presentation were fasting, hypoglycemia, hepatomegaly slight hypotonia in infancy and delayed growth. Although in most of the patients their signs and symptoms ameliorated after childhood, significant complications were observed in some 20% of the patients. Consequently, a life long follow up of GSD-III patients is required.
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PMID:Glycogen storage disease type III in Israel: presentation and long-term outcome. 2471 97

Glycogen storage disease type IV (GSD-IV), or Andersen disease, is a rare autosomal recessive disorder that results from the deficiency of glycogen branching enzyme (GBE). This in turn results in accumulation of abnormal glycogen molecules that have longer outer chains and fewer branch points. GSD-IV manifests in a wide spectrum, with variable phenotypes depending on the degree and type of tissues in which this abnormal glycogen accumulates. Typically, GSD-IV presents with rapidly progressive liver cirrhosis and death in early childhood. However, there is a severe congenital neuromuscular variant of GSD-IV that has been reported in the literature, with fewer than 20 patient cases thus far. We report an unusual case of GSD-IV neuromuscular variant in a late preterm female infant who was born to non-consanguineous healthy parents with previously healthy children. Prenatally, our patient was found to have decreased fetal movement and polyhydramnios warranting an early delivery. Postnatally, she had severe hypotonia and respiratory failure, with no hepatic or cardiac involvement. Extensive metabolic and neurological workup revealed no abnormalities. However, molecular analysis by whole-exome sequencing revealed two pathogenic variants in the GBE1 gene. Our patient was thus a compound heterozygote of the two pathogenic variants: one of these was inherited from the mother [p.L490WfsX5 (c.1468delC)], and the other pathogenic variant was a de novo change [p.E449X (c.1245G>T)]. As expected in GSD-IV, diffuse intracytoplasmic periodic acid-Schiff-positive, diastase-resistant inclusions were found in the cardiac myocytes, hepatocytes, and skeletal muscle fibers of our patient.
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PMID:Case of Neonatal Fatality from Neuromuscular Variant of Glycogen Storage Disease Type IV. 3031 Nov 41