title: Glycogen storage disease-like phenotype with central nervous system involvement in a PGM1-CDG patient.
abstract: OBJECTIVE
  A 10-year-old boy presented with cleft palate, hepatopathy, cholecystolithiasis, myopathy, coagulopathy, hyperlipidemia, hypoglycemia, hyperuricemia, short stature, obesity, hypothyroidism, microcephaly and mild intellectual disability. The multi-systemic manifestation involving certain distinct clinical features prompted us to search for a subtype of congenital disorders of glycosylation (CDG).
  
  
  METHODS
  The patient was screened for CDG by examining the distribution of transferrin (TRF) and apolipoprotein C-III (ApoC-III) sialylated isoforms using isoelectric focusing of serum. This was followed by spectrophotometric measurement of phosphoglucomutase 1 (PGM1) activity in fibroblasts and molecular analysis including sequencing and PCR-RFLP of PGM1 gene. Selected bioinformatics tools were used to evaluate the data.
  
  
  RESULTS
  Increased relative levels of di-, mono- and asialotransferrin reflected a defect of N-glycosylation in the patient. Markedly decreased activity of PGM1 corresponding to less than 5% of control´s was found. Sequencing of PGM1 gene revealed the presence of two heterozygous missense mutations c.1010C>T (p.T337M) and c.1508G>A (p.R503Q), whose pathogenicity was confirmed by in silico analysis.
  
  
  CONCLUSIONS
  We report the first Czech patient with a glycosylation disorder due to PGM1 deficiency. Compared to the described cases, no dilated cardiomyopathy was noted in our patient. However, he suffered from a mild neurological impairment, which is an uncommon feature that extends the phenotype associated with PGM1-CDG. Lactose-rich diet, which was previously reported to have ameliorated the clinical symptoms in some PGM1-CDG patients, did not result in any improvement in our patient.
authors.affiliation: Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic.
authors.forename: Nina
authors.initials: N
authors.lastname: Ondruskova
authors.affiliation: Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic.
authors.forename: Tomas
authors.initials: T
authors.lastname: Honzik
authors.affiliation: Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic.
authors.forename: Alzbeta
authors.initials: A
authors.lastname: Vondrackova
authors.affiliation: Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic.
authors.forename: Marketa
authors.initials: M
authors.lastname: Tesarova
authors.affiliation: Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic.
authors.forename: Jiri
authors.initials: J
authors.lastname: Zeman
authors.affiliation: Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic.
authors.forename: Hana
authors.initials: H
authors.lastname: Hansikova
mesh_terms: D002490:Central Nervous System / Q000503:physiopathology; D002648:Child; D006008:Glycogen Storage Disease / Q000150:complications* / Q000235:genetics; D006801:Humans; D008607:Intellectual Disability / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D008831:Microcephaly / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D020125:Mutation, Missense; D010641:Phenotype; D010733:Phosphoglucomutase / Q000235:genetics
chemical_list: C488050:PGM1 protein, human; D010733:Phosphoglucomutase