1/42. Early-onset fetal hydrops and muscle degeneration in siblings due to a novel variant of type IV glycogenosis. We report on 3 consecutive sib fetuses, presenting at 13, 12, and 13 weeks of gestation, respectively, with fetal hydrops, limb contractures, and akinesia. autopsy of the first fetus showed subcutaneous fluid collections and severe degeneration of skeletal muscle. Histologic studies demonstrated massive accumulation of diastase-resistant periodic acid-Schiff-positive material in the skeletal muscle cells and epidermal keratinocytes of all 3 fetuses. Enzyme studies of fibroblasts from the 3rd fetus showed deficient activity of glycogen brancher enzyme, indicating that this is a new, severe form of glycogenosis type IV with onset in the early second trimester. ( info) |
| Deficiency of glycogen branching enzyme activity causes glycogen storage disease type IV (GSD-IV). Clinically, GSD-IV has variable clinical presentations ranging from a fatal neonatal neuromuscular disease, to a progressive liver cirrhosis form, and to a milder liver disease without progression. Current methods for prenatal and postnatal diagnosis are based on an indirect method of measuring the enzyme activity, which has a limited sensitivity and cannot be used to distinguish patients with these variable clinical phenotypes. In this study, a GSD-IV family with a non-progressive hepatic form of the disease requested prenatal diagnosis. Determination of the branching enzyme activity in cultivated amniocytes showed 20 per cent residual activity overlapping with the level detected in the heterozygotes. mutation analysis revealed that the fetus carried two mutant alleles, L224P and Y329S, the same as the proband of this family. The fetus was predicted to be affected and postnatally his clinical presentation is consistent with the diagnosis. We conclude that dna mutation analysis should be used in the prenatal diagnosis of GSD-IV, especially in the situation of high residual enzyme activity. ( info) |
| 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. ( info) |
4/42. A novel missense mutation in the glycogen branching enzyme gene in a child with myopathy and hepatopathy. We have identified a novel missense mutation in the gene for glycogen branching enzyme (GBE 1) in a 16-month-old infant with a combination of hepatic and muscular features, an atypical clinical presentation of glycogenosis type IV (GSD IV). The patient was heterozygous for a G-to-A substitution at codon 524 (R524Q), changing an encoded arginine (CGA) to glutamine (CAA), while the GBE1 gene on the other allele was not expressed. This case broadens the spectrum of mutations in patients with GSD IV and confirms the clinical and molecular heterogeneity of this disease. ( info) |
5/42. Type IV glycogenosis - a study of two cases. Liver biopsy materials of two siblings with type IV glycogenosis were studied by light and electron microscopy. Biochemical analysis was added using autopsy material in one of the two cases. Two kinds of polysaccharides were noted not only in the cardiac muscle, skeletal muscles, smooth muscles and reticuloendothelial cells, but also in the neutrophils and platelets. One was glycogen and the other was similar to amylopectin. Ultrastructurally, a large amount of fibrils, 60 A in width, glycogen rosettes and glycogen granules were detected in those cells. Branching glycosyltransferase deficiency was biochemically confirmed in one case examined. ( info) |
6/42. Rectal biopsy in type 4 glycogenosis. An ultrastructural cytochemical study. Rectal biopsy material from a patient with type 4 glycogenosis was studied by ultrastructural cytochemical methods. The diagnosis of the disease was made on the basis of the patient's clinical history, the autopsy findings, and the histopathological features. Numerous large macrophages were observed in the rectal mucosa. They contained large vacuoles filled with filamentous material and small granules. This amylopectin was stained by the Thiery method (periodic acid-thiocarbohydrazide-silver proteinate) after 18 hours of exposure to thiocarbohydrazide; only 30 minutes was sufficient to demonstrate seemingly normal beta-glycogen particles in epithelial cells. ( info) |
7/42. Type IV glycogen-storage disease. light-microscopic, electron-microscopic, and enzymatic study. The case of a 14-month-old Latin American girl with the diagnosis of Type IV glycogen-storage disease is reported. The diagnosis was reached on the basis of the typical clinical manifestations, the light- and electron-microscopic findings, and the demonstration of absence of the branching enzyme alpha-1,4-glucan:alpha-1,4-glucan 6-glucosyl transferase in the liver and in the cultured skin fibroblasts. ( info) |
8/42. Novel missense mutations in the glycogen-branching enzyme gene in adult polyglucosan body disease. We describe the first non-Ashkenazi patient with adult polyglucosan body disease and decreased glycogen-branching enzyme (GBE) activity in leukocytes. Gene analysis revealed compound heterozygosity for two novel missense mutations Arg515His and Arg524Gln in the GBE gene. Both missense mutations are predicted to impair GBE activity. This is the first identification of GBE mutations underlying adult polyglucosan body disease in a non-Ashkenazi family, and confirms that adult glycogen storage disease type iv can manifest clinically as adult polyglucosan body disease. ( info) |
| A 13 year old patient with juvenile type IV glycogen storage disease died of the complications of hepatocellular carcinoma. To our knowledge this is the first reported case of hepatocellular carcinoma in association with type IV glycogen storage disease. ( info) |
| We report of an infant with neonatal glycogen storage disease type iv (GSD IV) who was examined for severe hypotonia and cardiomyopathy. On the muscle biopsy there were many fibers with diastase-resistant polyglucosan bodies. Glycogen branching enzyme (GBE1) activity in the muscle was markedly reduced. The infant had a homozygous single nucleotide deletion in the open reading frame of GBE1 gene. ( info) |