title: Recurrent episodes of myoglobinuria, mental retardation and seizures but no hemolysis in two brothers with phosphoglycerate kinase deficiency.
abstract: We report two brothers with mild intellectual deficiency, exercise intolerance, rhabdomyolysis, seizures and no hemolysis. Phosphoglycerate kinase (PGK) activity was strongly decreased in their red blood cells. Subsequent molecular analysis of PGK1 revealed hemizygosity for a novel mutation c.756 + 3A > G, in intron 7. Analysis of the effect of this mutation on pre-mRNA processing demonstrated markedly decreased levels of normal PGK1 mRNA. In addition, the c.756 + 3A > G change resulted in abnormally spliced transcripts. If translated, these transcripts mostly encode for C-terminally truncated proteins. The consequences of the c.756 + 3A > G mutation is discussed, as well as the genotype-to-phenotype correlation with regard to previously described mutations (PGK Fukuroi and PGK Antwerp), which also result in C-terminal truncated proteins.
authors.affiliation: Neuromuscular Reference Centre, Department of Pediatric Neurology, Hôpital Erasme, Université Libre de Bruxelles (U.L.B.), Brussels, Belgium; Neuromuscular Reference Centre, Department of Pediatric Neurology, Queen Fabiola Children's University Hospital, Université Libre de Bruxelles (U.L.B.), Brussels, Belgium. Electronic address: sacoppen@ulb.ac.be.
authors.forename: Sandra
authors.initials: S
authors.lastname: Coppens
authors.affiliation: Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, The Netherlands; Department of Biology, Faculty of Medicine and Dentistry, Palacký University Olomouc, Olomouc, Czech Republic.
authors.forename: Pavla
authors.initials: P
authors.lastname: Koralkova
authors.affiliation: Neuromuscular Reference Centre, Department of Pediatric Neurology, Hôpital Erasme, Université Libre de Bruxelles (U.L.B.), Brussels, Belgium.
authors.forename: Alec
authors.initials: A
authors.lastname: Aeby
authors.affiliation: Department of Biology, Faculty of Medicine and Dentistry, Palacký University Olomouc, Olomouc, Czech Republic.
authors.forename: Renata
authors.initials: R
authors.lastname: Mojzikova
authors.affiliation: Neuromuscular Reference Centre, Department of Pediatric Neurology, Queen Fabiola Children's University Hospital, Université Libre de Bruxelles (U.L.B.), Brussels, Belgium.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Deconinck
authors.affiliation: Department of Neuropathology and Reference Centre for Neuromuscular Pathology, Brugmann University Hospital (CHU-Brugmann), Université Libre de Bruxelles (U.L.B.), Brussels, Belgium.
authors.forename: Hazim
authors.initials: H
authors.lastname: Kadhim
authors.affiliation: Neuromuscular Reference Centre, Department of Pediatric Neurology, Hôpital Erasme, Université Libre de Bruxelles (U.L.B.), Brussels, Belgium.
authors.forename: Richard
authors.initials: R
authors.lastname: van Wijk
mesh_terms: D000293:Adolescent; D040181:Genetic Diseases, X-Linked / Q000150:complications / Q000175:diagnosis* / Q000235:genetics*; D005838:Genotype; D006461:Hemolysis; D006801:Humans; D008607:Intellectual Disability / Q000150:complications*; D008297:Male; D008661:Metabolism, Inborn Errors / Q000150:complications / Q000175:diagnosis* / Q000235:genetics*; D018482:Muscle, Skeletal / Q000473:pathology; D009154:Mutation; D009212:Myoglobinuria / Q000150:complications*; D010641:Phenotype; D010735:Phosphoglycerate Kinase / Q000172:deficiency* / Q000235:genetics / Q000648:ultrastructure; D012640:Seizures / Q000150:complications*; D035781:Siblings
chemical_list: D010735:Phosphoglycerate Kinase
keywords: Metabolic myopathy; PGK; Phosphoglycerate kinase