title: Variability of disease spectrum in children with liver phosphorylase kinase deficiency caused by mutations in the PHKG2 gene.
abstract: Liver phosphorylase b kinase (PhK) deficiency (glycogen storage disease type IX), one of the most common causes of glycogen storage disease, is caused by mutations in the PHKA2, PHKB, and PHKG2 genes. Presenting symptoms include hepatomegaly, ketotic hypoglycemia, and growth delay. Clinical severity varies widely. Autosomal recessive mutations in the PHKG2 gene, which cause about 10-15% of cases, have been associated with severe symptoms including increased risk of liver cirrhosis in childhood. We have summarized the molecular, biochemical, and clinical findings in five patients, age 5-16 years, diagnosed with liver PhK deficiency caused by PHKG2 gene mutations. We have identified five novel and two previously reported mutations in the PHKG2 gene in these five patients. Clinical severity was variable among these patients. Histopathological studies were performed for four of the patients on liver biopsy samples, all of which showed signs of fibrosis but not cirrhosis. One of the patients (aged 9 years) developed a liver adenoma which later resolved. All patients are currently doing well. Their clinical symptoms have improved with age and treatment. These cases add to the current knowledge of clinical variability in patients with PHKG2 mutations. Long term studies, involving follow-up of these patients into adulthood, are needed.
authors.affiliation: Department of Pediatrics, Box 103856, Duke University Health System, Durham, NC 27710, USA. Electronic address: dbali@duke.edu.
authors.forename: Deeksha S
authors.initials: DS
authors.lastname: Bali
authors.affiliation: Department of Pediatrics, Box 103856, Duke University Health System, Durham, NC 27710, USA. Electronic address: jennifer.goldstein@duke.edu.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Goldstein
authors.affiliation: Department of Pediatrics, Box 103856, Duke University Health System, Durham, NC 27710, USA. Electronic address: keri.boyette@dm.duke.edu.
authors.forename: Keri
authors.initials: K
authors.lastname: Fredrickson
authors.affiliation: Clinical Molecular Diagnostic Laboratory, 4425 Ben Franklin Blvd, Duke University Health System, Durham, NC 27704, USA. Electronic address: catherine.rehder@duke.edu.
authors.forename: Catherine
authors.initials: C
authors.lastname: Rehder
authors.affiliation: Department of Pediatrics, Box 103856, Duke University Health System, Durham, NC 27710, USA. Electronic address: anne.boney@dm.duke.edu.
authors.forename: Anne
authors.initials: A
authors.lastname: Boney
authors.affiliation: Department of Pediatrics, Box 103856, Duke University Health System, Durham, NC 27710, USA. Electronic address: stephanie.austin@duke.edu.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Austin
authors.affiliation: Glycogen Storage Disease Program, PO Box 100296, University of Florida College of Medicine, Gainesville, FL 32610, USA. Electronic address: weinsda@peds.ufl.edu.
authors.forename: David A
authors.initials: DA
authors.lastname: Weinstein
authors.affiliation: University of Nebraska Medical Center, Munroe-Meyer Institute for Genetics & Rehabilitation, 985440 Nebraska Medical Center, USA. Electronic address: rlutz@unmc.edu.
authors.forename: Richard
authors.initials: R
authors.lastname: Lutz
authors.affiliation: Metabolic Genetics, Victorian Clinical Genetics Services, The Murdoch Children's Research Institute, Royal Children's Hospital Melbourne, Department of Paediatrics, University of Melbourne, Flemington Road, Parkville 3052, Australia. Electronic address: avihu.boneh@vcgs.org.au.
authors.forename: Avihu
authors.initials: A
authors.lastname: Boneh
authors.affiliation: Department of Pediatrics, Box 103856, Duke University Health System, Durham, NC 27710, USA. Electronic address: kishn001@mc.duke.edu.
authors.forename: Priya S
authors.initials: PS
authors.lastname: Kishnani
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D006008:Glycogen Storage Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006529:Hepatomegaly / Q000235:genetics / Q000473:pathology; D006801:Humans; D007003:Hypoglycemia / Q000235:genetics / Q000473:pathology; D007223:Infant; D008099:Liver / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009154:Mutation; D010764:Phosphorylase Kinase / Q000172:deficiency / Q000235:genetics*
chemical_list: D010764:Phosphorylase Kinase
keywords: Glycogen storage disease type IX; Hypoglycemia; Liver adenoma; PHKG2 gene; Phosphorylase b kinase deficiency