title: Muscle phosphorylase kinase deficiency: a neutral metabolic variant or a disease?
abstract: OBJECTIVE
  To examine metabolism during exercise in 2 patients with muscle phosphorylase kinase (PHK) deficiency and to further define the phenotype of this rare glycogen storage disease (GSD).
  
  
  METHODS
  Patient 1 (39 years old) had mild exercise-induced forearm pain, and EMG showed a myopathic pattern. Patient 2 (69 years old) had raised levels of creatine kinase (CK) for more than 6 months after statin treatment. Both patients had increased glycogen levels in muscle and PHK activity <11% of normal. Two novel pathogenic nonsense mutations were found in the PHKA1 gene. The metabolic response to anaerobic forearm exercise and aerobic cycle exercise was studied in the patients and 5 healthy subjects.
  
  
  RESULTS
  Ischemic exercise showed a normal 5-fold increase in plasma lactate (peak 5.7 and 6.9 mmol/L) but an exaggerated 5-fold increase in ammonia (peak 197 and 171 μmol/L; control peak range 60-113 μmol/L). An incremental exercise test to exhaustion revealed a blunted lactate response (5.4 and 4.8 mmol/L) vs that for control subjects (9.6 mmol/L; range 7.1-14.3 mmol/L). Fat and carbohydrate oxidation rates at 70% of peak oxygen consumption were normal. None of the patients developed a second wind phenomenon or improved their work capacity with an IV glucose infusion.
  
  
  CONCLUSIONS
  Our findings demonstrate that muscle PHK deficiency may present as an almost asymptomatic condition, despite a mild impairment of muscle glycogenolysis, raised CK levels, and glycogen accumulation in muscle. The relative preservation of glycogenolysis is probably explained by an alternative activation of myophosphorylase by AMP and P(i) at high exercise intensities.
authors.affiliation: Neuromuscular Research Unit, Department of Neurology, Rigshospitalet, Denmark. npreisler@hotmail.com
authors.forename: N
authors.initials: N
authors.lastname: Preisler
authors.forename: M C
authors.initials: MC
authors.lastname: Orngreen
authors.forename: A
authors.initials: A
authors.lastname: Echaniz-Laguna
authors.forename: P
authors.initials: P
authors.lastname: Laforet
authors.forename: E
authors.initials: E
authors.lastname: Lonsdorfer-Wolf
authors.forename: S
authors.initials: S
authors.lastname: Doutreleau
authors.forename: B
authors.initials: B
authors.lastname: Geny
authors.forename: H O
authors.initials: HO
authors.lastname: Akman
authors.forename: S
authors.initials: S
authors.lastname: Dimauro
authors.forename: J
authors.initials: J
authors.lastname: Vissing
mesh_terms: D000328:Adult; D000368:Aged; D000641:Ammonia / Q000097:blood; D001706:Biopsy; D050260:Carbohydrate Metabolism / Q000235:genetics; D003402:Creatine Kinase / Q000097:blood; D015444:Exercise; D005080:Exercise Test; D005542:Forearm / Q000098:blood supply; D014644:Genetic Variation; D006003:Glycogen / Q000378:metabolism; D006008:Glycogen Storage Disease / Q000201:enzymology*; D006012:Glycogen Storage Disease Type V / Q000097:blood / Q000201:enzymology*; D050261:Glycogenolysis; D006801:Humans; D007511:Ischemia; D007773:Lactates / Q000097:blood; D050356:Lipid Metabolism / Q000235:genetics; D008297:Male; D018482:Muscle, Skeletal / Q000201:enzymology* / Q000378:metabolism; D010101:Oxygen Consumption; D010146:Pain / Q000209:etiology; D010641:Phenotype; D010764:Phosphorylase Kinase / Q000172:deficiency* / Q000235:genetics; D012039:Regional Blood Flow
chemical_list: D007773:Lactates; D000641:Ammonia; D006003:Glycogen; D010764:Phosphorylase Kinase; D003402:Creatine Kinase