1/13. Acute renal failure in a patient with phosphofructokinase deficiency.A 16-year-old Caucasian girl was admitted to hospital with acute renal failure and hemolytic anemia due to rhabdomyolysis following a 3-km walk. (31)P-magnetic resonance spectroscopy provided characteristic spectra of type VII glycogen storage disease (phosphofructokinase deficiency).- - - - - - - - - - ranking = 1keywords = storage disease, storage (Clic here for more details about this article) |
2/13. Fatal familial infantile glycogen storage disease: multisystem phosphofructokinase deficiency.An infant girl of consanguinous Bedouin parents suffered from fatal early onset of progressive generalized muscle weakness. Her older brother suffered from similar weakness and cardiomyopathy, which led to his death at the age of 21 months. A muscle biopsy performed on the propositus at the age of 9 months was PAS-negative, and showed nonspecific myopathic changes. A second muscle biopsy, performed at 21 months of age, a few days before her death, and postmortem study of heart and liver, disclosed excessive extralysosomal glycogen storage and reduced phosphofructokinase-1 (PFK-1) activity. Because the genes encoded for PFK-1 in liver and muscle are located on separate chromosomes, the reduced enzyme activity in both tissues could not be related to a single mutation for this enzyme. Activity of 6-phosphofructose-2-kinase (PFK-2), a recently discovered physiological activator to all PFK-1 isozymes, was normal in the liver. The possibility that this multisystem PFK-1 deficiency may be related to the absence of a yet unknown activator, common to all PFK-1 isozymes, is discussed.- - - - - - - - - - ranking = 4.1287611667112keywords = storage disease, storage, enzyme (Clic here for more details about this article) |
3/13. Phosphofructokinase deficiency (Tarui disease) associated with hepatic glucuronyltransferase deficiency (Gilbert's syndrome): a case and family study.Tarui disease is a rare, genetically determined glycogen storage myopathy caused by the total lack of phosphofructokinase (PFK) enzymatic activity in the muscles and partially deficient enzymatic activity in the erythrocytes. We describe a patient with this disorder, who presented with exercise intolerance, painful cramps, elevation of muscle enzyme levels in the serum, compensated hemolysis with paradoxically elevated hemoglobin levels and gout with overproduction of uric acid. This patient had a partial hepatic uridine diphosphoglucuronate-glucuronyltransferase deficiency (Gilbert's syndrome). The coexistence of these two enzymatic deficiencies resulted in a complex clinical picture, especially during and after muscular effort. Screening of the patient's family revealed asymptomatic PFK deficiency in the erythrocytes of both parents and sister.- - - - - - - - - - ranking = 0.12701918064445keywords = storage, enzyme (Clic here for more details about this article) |
4/13. Characterization of the enzymatic defect in late-onset muscle phosphofructokinase deficiency. New subtype of glycogen storage disease type vii.Human phosphofructokinase (PFK) exists in tetrameric isozymic forms, at least in vitro. Muscle and liver contain homotetramers M4 and L4, respectively, whereas red cells contain five isozymes composed of M (muscle) and L (liver) type subunits, i.e., M4, M3L, M2L2, and ML3, and L4. Homozygous deficiency of muscle PFK results in the classic glycogen storage disease type vii characterized by exertional myopathy and hemolytic syndrome beginning in early childhood. The genetic lesion results in a total and partial loss of muscle and red cell PFK, respectively. Characteristically, the residual red cell PFK from the patients consists of isolated L4 isozyme; the M-containing hybrid isozymes are completely absent. In this study, we investigated an 80-yr-old man who presented with a 10-yr history of progressive weakness of the lower limbs as the only symptom. The residual red cell PFK showed the presence of a few M-containing isozymes in addition to the predominant L4 species, indicating that the genetic lesion is a "leaky" mutation of the gene coding for the M subunit. The presence of a small amount of enzyme activity in the muscle may account for the atypical myopathy in this patient.- - - - - - - - - - ranking = 5.0017419860667keywords = storage disease, storage, enzyme (Clic here for more details about this article) |
5/13. Myogenic hyperuricemia. A common pathophysiologic feature of glycogenosis types III, V, and VII.To identify the mechanism of hyperuricemia in glycogen storage diseases (glycogenoses) that affect muscle, we studied the effects of exercise and prolonged rest on purine metabolism in two patients with glycogenosis type III (debrancher deficiency), one patient with type V (muscle phosphorylase deficiency), and one patient with type VII (muscle phosphofructokinase deficiency). All had hyperuricemia except for one patient with glycogenosis type III. plasma concentrations of ammonia, inosine, and hypoxanthine increased markedly in all the patients after mild leg exercise on a bicycle ergometer. The plasma urate concentrations also increased, but with a delayed response. Urinary excretion of inosine, hypoxanthine, and urate increased greatly after exercise, consistently with the increases in plasma levels. hypoxanthine and urate concentrations were extremely high in the plasma and urine of the patient with glycogenosis type VII. With bed rest, the plasma hypoxanthine level returned to normal within a few hours, and the plasma urate concentration decreased from 18.6 to 10.6 mg per deciliter (1106 to 630 mumol per liter) within 48 hours. Similarly, the urinary excretion of these purine metabolites was reduced by bed rest. These findings indicate that muscular exertion in patients with glycogenosis types III, V, and VII causes excessive increases in blood ammonia, inosine, and hypoxanthine due to accelerated degradation of muscle purine nucleotides. These purine metabolites subsequently serve as substrates for the synthesis of uric acid, leading to hyperuricemia.- - - - - - - - - - ranking = 1keywords = storage disease, storage (Clic here for more details about this article) |
6/13. Muscle phosphofructokinase deficiency: abnormal polysaccharide in a case of late-onset myopathy.A 61-year-old woman with muscle phosphofructokinase (PFK) deficiency had mild limb weakness all her life but no cramps or myoglobinuria. For 5 years the limb weakness progressed. In muscle, PFK activity was 1% of normal and glycogen concentration was elevated (2.13%). By light microscopy, a minor component of the accumulated glycogen appeared as PAS-positive, diastase-resistant inclusions in 10% of muscle fibers. The inclusions had a filamentous fine structure that resembled the abnormal long-chain glycogen of brancher enzyme deficiency. iodine absorption spectra of both the inclusions and a diastase-resistant fraction of isolated glycogen resembled amylopectin. The abnormal polysaccharide in PFK deficiency may be related to greatly elevated concentration of muscle glucose-6-phosphate, an activator of the chain-elongating enzyme glycogen synthase.- - - - - - - - - - ranking = 0.0034839721334654keywords = enzyme (Clic here for more details about this article) |
7/13. Nonsense mutation in the phosphofructokinase muscle subunit gene associated with retention of intron 10 in one of the isolated transcripts in Ashkenazi Jewish patients with Tarui disease.Mutations in the human phosphofructokinase muscle subunit gene (PFKM) are known to cause myopathy classified as glycogenosis type VII (Tarui disease). Previously described molecular defects include base substitutions altering encoded amino acids or resulting in abnormal splicing. We report a mutation resulting in phosphofructokinase deficiency in three patients from an Ashkenazi Jewish family. Using a reverse transcription PCR assay, PFKM subunit transcripts differing by length were detected in skeletal muscle tissue of all three affected subjects. In the longer transcript, an insertion of 252 nucleotides totally homologous to the structure of the 10th intron of the PFKM gene was found separating exon 10 from exon 11. In addition, two single base transitions were identified by direct sequencing: [exon 6; codon 95; CGA (Arg) to TGA (stop)] and [exon 7; codon 172; ACC (Thr) to ACT (Thr)] in either transcript. Single-stranded conformational polymorphism and restriction enzyme analyses confirmed the presence of these point substitutions in genomic dna and strongly suggested homozygosity for the pathogenic allele. The nonsense mutation at codon 95 appeared solely responsible for the phenotype in these patients, further expanding genetic heterogeneity of Tarui disease. Transcripts with and without intron 10 arising from identical mutant alleles probably resulted from differential pre-mRNA processing and may represent a novel message from the PFKM gene.- - - - - - - - - - ranking = 0.0017419860667327keywords = enzyme (Clic here for more details about this article) |
8/13. A new variant case of muscle phosphofructokinase deficiency, coexisting with gastric ulcer, gouty arthritis, and increased hemolysis.Muscle phosphofructokinase (PFK) deficiency includes both clinically and genetically heterogeneous conditions. A 22-year-old man with muscle PFK deficiency due to previously unrecognized mutation was admitted because of gastric ulcer. He had noticed mild fatigability on vigorous exercise, but had never experienced painful cramps and myoglobinuria. His history included five time relapses of gastric ulcer and gouty arthritis at ages 19 and 21 years. His laboratory data showing impaired muscle glycolysis, increased hemolysis, and myogenic hyperuricemia had aspects in common with those reported for the classic form of this disease, except that lactate concentrations in his blood increased considerably after exercise. The mutant PFK enzyme of this patient, who was demonstrated to have a missense mutation, could exert some catalytic activity that permitted glycolytic flux in vivo, thus leading to the absence of typical myopathic symptoms. The association of relapsing gastric ulcer with muscle PFK deficiency was detected for the first time. There is a possibility that oxygen radical-induced tissue damage resulting from increased hypoxanthine on exertion plays a role in the pathogenesis of ulceration, since the patient is more tolerant to exercise than reported cases with the classic form of muscle PFK deficiency.- - - - - - - - - - ranking = 0.0017419860667327keywords = enzyme (Clic here for more details about this article) |
9/13. A 5' splice junction mutation leading to exon deletion in an Ashkenazic Jewish family with phosphofructokinase deficiency (Tarui disease).A deficiency of the muscle isoform of the enzyme, phosphofructokinase (PFK, EC 2.7.1.11), leads to an illness (glycogenosis, Type VII) characterized by myopathy and hemolysis. A patient with this disease and an affected sister were found to have a G to A substitution at the 5' donor site of intron 5 of the PFK-M gene. This mutation led to a splicing defect: a complete deletion of the preceding exon in the patient's mRNA. The patient, an affected sister, and related and unrelated family members, who were of Ashkenazic Jewish background, were screened for the mutation by denaturing gradient gel electrophoresis and by allele specific hybridization of genomic dna. The affected sisters are homozygous for the mutation, and their children, who are unaffected, are heterozygous. The only previously characterized genetic defect in this disease, found in a Japanese patient, was a G to T mutation at the beginning of intron 15 with splicing to a cryptic site within exon 15 (1). Both mutations lead to inframe deletions, but of different parts of the protein. The differences between the two aberrant proteins may account for clinical differences between our patients and the Japanese patient.- - - - - - - - - - ranking = 0.0017419860667327keywords = enzyme (Clic here for more details about this article) |
10/13. Late-onset muscle weakness in partial phosphofructokinase deficiency: a unique myopathy with vacuoles, abnormal mitochondria, and absence of the common exon 5/intron 5 junction point mutation.Three patients (ages 51, 59, and 79) from two generations of an Ashkenazi Jewish family had partial (33% activity) phosphofructokinase (PFK) deficiency that presented with fixed muscle weakness after the age of 50 years. MR spectroscopy revealed accumulation of phosphomonoesters during exercise. Muscle biopsy showed a vacuolar myopathy with increased autophagic activity and several ragged-red and cytochrome c oxidase-negative fibers. The older patient, age 79 at biopsy, had several necrotic fibers. Electron microscopy revealed subsarcolemmal and intermyofibrillar glycogen accumulation and proliferation of mitochondria with paracrystalline inclusions, probably related to reduced availability of energy due to impaired glycolysis. The common point mutation of exon 5/intron 5 junction seen in Jewish Ashkenazi patients with PFK deficiency was excluded. We conclude that late-onset fixed muscle weakness occurs in partial PFK deficiency and it may represent the end result of continuing episodes of muscle fiber destruction. Partial enzyme deficiency in two successive generations suggests a unique molecular mechanism.- - - - - - - - - - ranking = 0.0017419860667327keywords = enzyme (Clic here for more details about this article) |
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