1/81. A large Alu-mediated deletion, identified by PCR, as the molecular basis for glycogen storage disease type ii (GSDII).glycogen storage disease type ii (GSDII) is an autosomal recessive disorder resulting from inherited deficiency of the enzyme lysosomal acid alpha-glucosidase. Over 40 different mutations have been described but no large deletions have been previously identified. We now describe a homozygous large (9-kb) deletion extending from IVS 15 to 4 kb downstream of the terminal exon (exon 20), detected by polymerase chain reaction (PCR)-based methods. The deletion was initially suspected because of failure to amplify a contiguous group of exons by PCR. We hypothesized an Alu/Alu recombination, based on our prior demonstration by Southern blotting of alu elements in the regions potentially flanking the deletion. Additional sequence analysis of genomic fragments confirmed the presence of alu elements and allowed the design of flanking primers for PCR amplification. Amplification resulted in a smaller than normal fragment (0.7 vs. 10 kb) in homozygosity in the proband and in heterozygosity in her parents. Cloning and sequencing of the smaller than normal 0.7-kb deletion fragment revealed an Alu/Alu deletion junction. In heterozygosity this deletion would not be detected by currently standard PCR mutation detection methods. Based on other Alu-mediated deletions, this deletion is likely to be recurrent and should be screened for in all non-consanguineous GSDII patients, particularly when only one mutation has been identified and none of the 12 single-nucleotide polymorphisms in the deleted region are heterozygous. These observations also suggest that initial characterization of genes at disease-causing loci should include a search for Alu and other repetitive elements to facilitate subsequent PCR-based mutation analysis.- - - - - - - - - - ranking = 1keywords = storage disease, storage, enzyme (Clic here for more details about this article) |
2/81. An interesting case of infant sudden death: severe hypertrophic cardiomyopathy in Pompe's disease.glycogen storage disease type ii (Pompe's disease) is a rare inherited metabolic disorder, which often leads to infantile death from severe cardiomyopathy. This case of sudden death illustrates the features of the cardiac findings in the disorder, resulting from massive lysosomal accumulation of glycogen in the heart and other tissues. Pompe's disease should be considered in cases of unexplained infantile cardiomyopathy.- - - - - - - - - - ranking = 0.19995010756153keywords = storage disease, storage (Clic here for more details about this article) |
3/81. Increased occurrence of cleft lip in glycogen storage disease type ii (GSDII): exclusion of a contiguous gene syndrome in two patients by presence of intragenic mutations including a novel nonsense mutation Gln58Stop.Genetic deficiency of lysosomal acid alpha-glucosidase (acid maltase) results in the autosomal recessive disorder glycogen storage disease type ii (GSDII) in which intralysosomal accumulation of glycogen primarily affects function of skeletal and cardiac muscle. During an earlier review we noted 3 in 100 cases of GSDII with incidental description of cleft lip. In addition, we identified 2 of 35 GSDII patients referred to us for molecular studies with co-occurence of cleft lip, considerably greater than the estimated frequency of nonsyndromic cleft lip with or without cleft palate of 1 in 700 to 1,000. Because several lines of evidence support a minor cleft lip/palate (Cl/P) locus on chromosome 17q close to the locus for GSDII, we defined the molecular basis for the GSDII in these two patients to determine if they represented a contiguous gene syndrome. Patient I (of Dutch descent) was homozygous and the parents heterozygous for an intragenic deletion of exon 18 (deltaex18), common in Dutch patients. Patient II was heterozygous for delta525T, a mutation also common in Dutch patients and a novel nonsense mutation (172 [corrected] C-->T; Gln58Stop) in exon 2, the first coding exon. The mother was heterozygous for the delta525T and the father for the 172 [corrected] C-->T; Gln58Stop. The finding that both patients carried intragenic mutations eliminates a contiguous gene syndrome. Whereas the presence of cleft lip/cleft palate in a patient with GSDII could be coincidental, these co-occurences could represent a modifying action of acid alpha-glucosidase deficiency on unlinked or linked genes that result in increased susceptibility for cleft lip.- - - - - - - - - - ranking = 0.99975053780763keywords = storage disease, storage (Clic here for more details about this article) |
4/81. adult glycogenosis II with paracrystalline mitochondrial inclusions and Hirano bodies in skeletal muscle.Hirano bodies constitute eosinophilic intracytoplasmic inclusions, typically seen in the central nervous system, where they are related to senility and certain dementias such as Alzheimer's disease or the Parkinson-dementia complex. They have been found in different tissues of experimental animals and, on rare occasions, in extraocular muscles of elderly individuals. However, to our knowledge they have not been described in skeletal muscle in locations other than extraocular muscles or associated with muscle pathology. Glycogenosis II or Pompe's disease, is a metabolic disorder caused by acid maltase deficiency and is characterized by glycogen accumulation in lysosomes in various tissues, including skeletal muscle. There are three clinical forms depending on age at onset, the most frequent being the childhood form. We present the histopathological and ultrastructural findings of a muscle biopsy performed in a case of the adult form of glycogenosis II which showed, in addition to characteristic lysosomal glycogen storage, paracrystalline mitochondrial inclusions and, as an exceptional finding, intracytoplasmic Hirano bodies in some muscle fibres.- - - - - - - - - - ranking = 0.016402761854848keywords = storage (Clic here for more details about this article) |
5/81. hydrocephalus associated with glycogen storage disease type ii (Pompe's disease).The authors describe a case of hydrocephalus in an 8-month, 2-week-old infant who had been previously diagnosed with glycogen storage disease type ii. Cranial imaging revealed no evidence of obstruction within the ventricular system. This case adds to the central nervous system complications associated with this disorder. Several possible mechanisms for the hydrocephalus observed in this infant are discussed.- - - - - - - - - - ranking = 0.99975053780763keywords = storage disease, storage (Clic here for more details about this article) |
6/81. Acid maltase deficiency (type II glycogenosis). Morphological and biochemical study of a childhood phenotype.Pathological and biochemical data are reported on a 4(4)/12-year-old male patient with a severe myopathic disorder, hepatomegaly, recurrent pulmonary infections ending fatally. Combined morphological and enzymatic studies on muscle biopsy led to the diagnosis of acid maltase deficiency (Type II glycogenosis). On post mortem examination, lysosomal glycogen storage is found in skeletal muscles and liver, while heart and central nervous sytem are spared. Both hydrolytic and transferase activities of acid maltase are absent in cultured fibroblasts, heart, liver and postmortem skeletal muscles. That in the biopsied skeletal muscle only, the transferase activity alone is deficient while the hydrolytic function is maintained at low normal levels correlates well with the abnormal structure of the glycogen stored in that muscle. However, these findings on biopsied muscle cannot be reconciled with the absence of both functions and the presence of normal glycogen in other biopsied tissues or in postmortem specimens from the same patient.- - - - - - - - - - ranking = 0.016402761854848keywords = storage (Clic here for more details about this article) |
7/81. Late infantile acid maltase deficiency: a case report.A five-year-old boy with late-infantile (juvenile) form of acid maltase deficiency is presented. His symptoms were restricted to skeletal muscle. There is commonly a correlation between the amount of residual acid maltase activity and the severity of the clinical picture. Although the residual enzyme level was very low in our patient, no progression of his neurological findings have been observed during the follow-up period of two years.- - - - - - - - - - ranking = 0.00024946219236747keywords = enzyme (Clic here for more details about this article) |
8/81. Aberrant splicing at catalytic site as cause of infantile onset glycogen storage disease type II (GSDII): molecular identification of a novel IVS9 ( 2GT-->GC) in combination with rare IVS10 ( 1GT-->CT).glycogen storage disease type ii (GSDII) results from deleterious mutations in acid alpha-glucosidase gene. To date several mutant alleles have been studied including missense and nonsense mutations, insertions, small and large deletions as well as splice site mutations. Apart from IVS1 (- 13-->G), 525delT, and Delta18, the other mutations are rare and often unique to single patients. Moreover, the molecular findings also observed in the different ethnic groups makes it difficult to attempt to correlate genotype and phenotype to explain the origin of clinical variability. Even though there are no conclusive genotype phenotype correlations, the in frame splice site mutations identified up until now have been found associated with the juvenile/adult onset of GSDII. In this study we describe a novel in frame splicing defect, IVS9 ( 2GT-->GC), identified in combination with the rare IVS10 ( 1GT-->CT) mutation in a patient with classic infantile GSDII disease. Because both mutations occur at the catalytic site region, it is likely that the alteration of both catalytic function and steric conformation of the enzyme may be responsible for the most severe form of the disease.- - - - - - - - - - ranking = 0.26581061717329keywords = storage disease, storage, enzyme (Clic here for more details about this article) |
9/81. The Mount Sinai Hospital clinicalpathological conference: a 45-year-old man with Pompe's disease and dilated cardiomyopathy.This is an unusual case of a 45-year-old man, born in ecuador, with evidence of profound left ventricular dysfunction, dilated cardiomyopathy and marked myocardial hypertrophy. Preceding events were advanced atrioventricular block (necessitating pacemaker implantation) and atrial flutter. The diagnosis of Pompe's disease was established by endomyocardial biopsy and appropriate staining, which indicated abnormal glycogen storage.- - - - - - - - - - ranking = 0.016402761854848keywords = storage (Clic here for more details about this article) |
10/81. liver transplantation for type Ib glycogenosis with reversal of cyclic neutropenia.We describe a case of glycogen storage disease type Ib in 32-year old male patient with poor metabolic control in spite of medical and nutritional management and the use of recombinant granulocyte stimulating factor. Because of this, liver transplantation was considered as a definitive treatment. We comment on the metabolic results of liver transplantation performed, with reversal of hypoglycemia, hyperuricemia, hypertriglyceridemia and cyclic neutropenia, all of which persist 4 years post-transplant. In view of this case, we believe that liver transplantation is a feasible option to consider in patients with type Ib glycogenosis as a definitive therapeutic procedure.- - - - - - - - - - ranking = 0.19995010756153keywords = storage disease, storage (Clic here for more details about this article) |
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