title: Intermittent and recurrent hepatomegaly due to glycogen storage in a patient with type 1 diabetes: genetic analysis of the liver glycogen phosphorylase gene (PYGL).
abstract: We report a 19-year-old woman who had a history of type 1 diabetes with recurrent glycogen accumulation in the liver. During her infantile period she presented with no hepatomegaly nor growth retardation. On admission she was diagnosed with diabetic ketoacidosis (DKA). She also had hepatomegaly and elevated transaminase levels, but these abnormalities had resolved after administration of insulin. However, 4 weeks after DKA marked hepatomegaly and elevated transaminases were reappeared with simultaneous hypoglycemia which suggested an impaired glycogenolysis in the extraordinary conditions. We supposed the partial deficiency of liver glycogen phosphorylase activity in this patient and analyzed the liver glycogen phosphorylase gene (PYGL). Deduced amino acid sequence of the PYGL in this patient was completely identical to that reported by Burwinkel et al. (Y15233), however, the nucleotide sequence of PYGL cDNA was heterozygous for substitutions at positions Asp339 (GAT to GAC) on exon 9 and Ala703 (GCT to GCC on exon 17, respectively. These SNPs were also screened in 51 Japanese normal subjects by PCR-based direct sequencing or PCR-RFLP method. The same genotype observed in this patient was detected in 2 of 51(3.9%) normal subjects. These results suggest that the structure of PYGL coding sequence in this patient is unlikely to account for her excessive liver glycogen accumulation. Further studies including genetic analysis on the promoter region of the gene are necessary to clarify the etiology of susceptibility to excessive liver glycogen storage in patients with type 1 diabetes.
authors.affiliation: Division of Endocrinology and Metabolism, St. Mary's Hospital, 422 Tsubukuhonmachi, Kurume, Fukuoka, Japan.
authors.forename: Masako
authors.initials: M
authors.lastname: Tomihira
authors.forename: Eiji
authors.initials: E
authors.lastname: Kawasaki
authors.forename: Hiromu
authors.initials: H
authors.lastname: Nakajima
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Imamura
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Sato
authors.forename: Michio
authors.initials: M
authors.lastname: Sata
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kage
authors.forename: Hideo
authors.initials: H
authors.lastname: Sugie
authors.forename: Kiyohide
authors.initials: K
authors.lastname: Nunoi
mesh_terms: D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000201:enzymology / Q000235:genetics; D005260:Female; D024981:Glycogen Phosphorylase / Q000235:genetics*; D006529:Hepatomegaly / Q000201:enzymology / Q000209:etiology* / Q000235:genetics*; D006801:Humans; D008099:Liver / Q000201:enzymology*; D020641:Polymorphism, Single Nucleotide
chemical_list: D024981:Glycogen Phosphorylase