JIMD Rep 2017 4;31:79-83. Epub 2016 May 4.

Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center (DUMC), Box 103856, Durham, NC, 27710, USA.

Many inborn errors of metabolism can cause cardiomyopathy. Cardiomyopathy associated with glycogen storage includes PRKAG2-associated glycogen storage disease (GSD), Danon disease, infantile-onset Pompe disease (GSD II), GSD III, GSD IV, and phosphofructokinase deficiency (Tarui disease or GSD VII).We present a 35-year-old female who presented with cardiomyopathy after a pregnancy complicated by primary hyperparathyroidism. Read More

Circ Cardiovasc Imaging 2015 Sep;8(9):e003637

From the Department of Cardiology, Seth G.S. Medical College & King Edward VII Memorial Hospital, Acharya Donde Marg, Parel, Mumbai, India.

Pediatr Int 2015 Aug 25;57(4):746-9. Epub 2015 Jun 25.

Department of Emergency and Critical Care Medicine, Cheng Hsin Rehabilitation Medical Center, Taipei, Taiwan.

Muscle phosphofructokinase (PFK) deficiency is a rare autosomal recessive disease. We report the case of a preterm female infant who was diagnosed with the infantile form of phosphofructokinase deficiency due to a lack of PFK activity in her muscles, manifesting at a corrected age of 1 month as floppy infant syndrome, congenital joint contracture, cleft palate and duplication of the pelvicalyceal system. She died at a corrected age of 6 months due to respiratory failure. Read More

Free Radic Biol Med 2015 Oct 19;87:98-112. Epub 2015 May 19.

Department of Pediatrics and Medicine, Neuromuscular Clinic, McMaster University, Hamilton, Ontario L8N 3Z5, Canada. Electronic address:

A unifying feature in the pathogenesis of aging, neurodegenerative disease, and lysosomal storage disorders is the progressive deposition of macromolecular debris impervious to enzyme catalysis by cellular waste disposal mechanisms (e.g., lipofuscin). Read More

Nature 2015 Jul 18;523(7558):111-4. Epub 2015 May 18.

Department of Cell and Tissue Biology, University of California, San Francisco, California 94143, USA.

Phosphofructokinase-1 (PFK1), the 'gatekeeper' of glycolysis, catalyses the committed step of the glycolytic pathway by converting fructose-6-phosphate to fructose-1,6-bisphosphate. Allosteric activation and inhibition of PFK1 by over ten metabolites and in response to hormonal signalling fine-tune glycolytic flux to meet energy requirements. Mutations inhibiting PFK1 activity cause glycogen storage disease type VII, also known as Tarui disease, and mice deficient in muscle PFK1 have decreased fat stores. Read More

Br J Radiol 2014 Jan 14;87(1033):20130467. Epub 2013 Nov 14.

Lysosomal storage diseases (LSDs) are a large group of genetic metabolic disorders that result in the accumulation of abnormal material, such as mucopolysaccharides, glycoproteins, amino acids and lipids, within cells. Since many LSDs manifest during infancy or early childhood, with potentially devastating consequences if left untreated, timely identification is imperative to prevent irreversible damage and early death. In this review, the key imaging features of the non-lipid or extralipid LSDs are examined and correlated with salient clinical manifestations and genetic information. Read More

Rev Neurol (Paris) 2013 Aug-Sep;169(8-9):613-24. Epub 2013 Sep 4.

Service de neurologie, HIA Desgenettes, 108, boulevard Pinel, 69275 Lyon cedex 3, France. Electronic address:

Introduction: Muscle phosphofructokinase deficiency, the seventh member of the glycogen storage diseases family, is also called Tarui's disease (GSD VII).

Methods: We studied two patients in two unrelated families with Tarui's disease, analyzing clinical features, CK level, EMG, muscle biopsy findings and molecular genetics features. Metabolic muscle explorations (forearm ischemic exercise test [FIET]; bicycle ergometer exercise test [EE]; 31P-nuclear magnetic resonance spectroscopy of calf muscle [31P-NMR-S]) are performed as appropriate. Read More

Rev Neurol 2013 Sep;57 Suppl 1:S65-73

Miami Children's Hospital, Miami, EE.UU.

Aim: To review the metabolic myopathies manifested only by crisis of myalgias, cramps and rigidity of the muscles with decreased voluntary contractions and normal inter crisis neurologic examination in children and adolescents.

Development: These metabolic myopathies are autosomic recessive inherited enzymatic deficiencies of the carbohydrates and lipids metabolisms. The end result is a reduction of intra muscle adenosine triphosphate, mainly through mitochondrial oxidative phosphorylation, with decrease of available energy for muscle contraction. Read More

Biol Chem 2013 Aug;394(8):977-93

Institute of Biochemistry, Molecular Biochemistry, Medical Faculty, University of Leipzig, Johannisallee 30, D-04103 Leipzig, Germany.

Although the crystal structures of prokaryotic 6-phosphofructokinase, a key enzyme of glycolysis, have been available for almost 25 years now, structural information about the more complex and highly regulated eukaryotic enzymes is still lacking until now. This review provides an overview of the current knowledge of eukaryotic 6-phosphofructokinase based on recent crystal structures, kinetic analyses and site-directed mutagenesis data with special focus on the molecular architecture and the structural basis of allosteric regulation. Read More

Biochem Biophys Res Commun 2012 Oct 17;427(1):133-7. Epub 2012 Sep 17.

Institute of Biochemistry, Medical Faculty, University of Leipzig, 04103 Leipzig, Germany.

Tarui disease is a glycogen storage disease (GSD VII) and characterized by exercise intolerance with muscle weakness and cramping, mild myopathy, myoglobinuria and compensated hemolysis. It is caused by mutations in the muscle 6-phosphofructokinase (Pfk). Pfk is an oligomeric, allosteric enzyme which catalyzes one of the rate-limiting steps of the glycolysis: the phosphorylation of fructose 6-phosphate at position 1. Read More

Mol Cell Probes 2012 Dec 16;26(6):243-7. Epub 2012 Mar 16.

Section of Medical Genetics, University of Pennsylvania, Philadelphia, PA, USA.

Hereditary muscle-type phosphofructokinase (PFK) deficiency causing intermittent hemolytic anemia and exertional myopathy due to a single nonsense mutation in PFKM has been previously described in English Springer and American Cocker Spaniels, Whippets, and mixed breed dogs. We report here on a new missense mutation associated with PFK deficiency in Wachtelhunds. Coding regions of the PFKM gene were amplified from genomic DNA and/or cDNA reverse-transcribed from RNA of EDTA blood of PFK-deficient and clinically healthy Wachtelhunds and control dogs. Read More

J Neurol Sci 2012 May 23;316(1-2):173-7. Epub 2012 Feb 23.

Unité de Morphologie Neuromusculaire Institut de Myologie, GH Pitié-Salpêtrière, Paris, France.

We describe a 41-year-old Moroccan woman with phosphofructokinase (PFK) deficiency who presented slowly progressive muscular weakness since childhood, without rhabdomyolysis episode or hemolytic anemia. Deltoid biopsy revealed massive glycogen storage in the majority of muscle fibers and polysaccharide deposits. PFK activity in muscle was totally absent. Read More

Neuromuscul Disord 2012 Apr 30;22(4):325-30. Epub 2011 Nov 30.

Department of Neurosciences, Psychiatry and Anaesthesiology University of Messina, Italy.

Muscle phosphofructokinase (PFKM) deficiency, a rare disorder of glycogen metabolism also known as glycogen storage disease type VII (GSDVII), is characterized by exercise intolerance, myalgias, cramps and episodic myoglobinuria associated with compensated hemolytic anaemia and hyperuricemia. We studied five patients with PFKM deficiency coming from different Italian regions. All probands showed exercise intolerance, hyperCKemia, cramps and myoglobinuria. Read More

Fortschr Neurol Psychiatr 2011 Oct 11;79(10):598-605; quiz 606. Epub 2011 Oct 11.

Am J Med Sci 2011 May;341(5):417-9

Sections of Digestive Diseases, Internal Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.

Phosphofructokinase deficiency is a rare disorder with less than 100 reported cases; the contribution of altered glucose metabolism in other tissues to the pathogenesis of the disease is not fully understood. The authors present a unique case of portal and mesenteric vein thrombosis in a 43-year-old man with a known case of phosphofructokinase deficiency. Read More

PLoS Genet 2009 Aug 21;5(8):e1000615. Epub 2009 Aug 21.

Center of Animal Biotechnology and Gene Therapy, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain.

Mutations in the gene for muscle phosphofructo-1-kinase (PFKM), a key regulatory enzyme of glycolysis, cause Type VII glycogen storage disease (GSDVII). Clinical manifestations of the disease span from the severe infantile form, leading to death during childhood, to the classical form, which presents mainly with exercise intolerance. PFKM deficiency is considered as a skeletal muscle glycogenosis, but the relative contribution of altered glucose metabolism in other tissues to the pathogenesis of the disease is not fully understood. Read More

Acta Myol 2007 Oct;26(2):105-7

Department of Neurosciences, Psychiatry and Anaesthesiology, University of Messina, Italy.

Phosphofructokinase deficiency (Tarui disease) was the first disorder recognized to directly affect glycolysis. Since the discovery of the disease, in 1965, a wide range of biochemical, physiological and molecular studies have greatly contributed to our knowledge concerning not only phosphofructokinase function in normal muscle but also on the general control of glycolysis and glycogen metabolism. Studies on phosphofructokinase deficiency vastly enriched the field of glycogen storage diseases, making a relevant improvement also in the molecular genetic area. Read More

Cardiology 2008 12;110(4):238-40. Epub 2007 Dec 12.

Second Medical Department, and Krankenanstalt Rudolfstiftung, Vienna, Austria.

Progressive heart valve thickening and shrinkage, and progressive muscle cramps have not been reported as manifestations of glycogenosis type VII (Tarui's disease). In a 72-year-old female, Tarui's disease was diagnosed in 1997, initially manifesting as simple partial seizures since 1977, anginal chest pain since 1982 and muscle cramps since 1983. During the following years, low voltage ECG, ectopic supraventricular tachycardia, thickening of the mitral valve, mitral valve insufficiency, enlarged left atrium, left ventricular hypertrophy and diastolic dysfunction also developed. Read More

Acta Myol 2007 Jul;26(1):35-41

Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA.

Am J Physiol Endocrinol Metab 2007 Sep 26;293(3):E794-801. Epub 2007 Jun 26.

Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA.

Phosphofructokinase is a key enzyme of glycolysis that exists as homo- and heterotetramers of three subunit isoforms: muscle, liver, and C type. Mice with a disrupting tag inserted near the distal promoter of the phosphofructokinase-M gene showed tissue-dependent differences in loss of that isoform: 99% in brain and 95-98% in islets, but only 50-75% in skeletal muscle and little if any loss in heart. This correlated with the continued presence of proximal transcripts specifically in muscle tissues. Read More

World J Gastroenterol 2007 May;13(18):2541-53

Division of Gastroenterology, Hepatology and Nutrition, Hacettepe University Children's Hospital, Ankara, Turkey.

Glycogen storage diseases (GSD) are inherited metabolic disorders of glycogen metabolism. Different hormones, including insulin, glucagon, and cortisol regulate the relationship of glycolysis, gluconeogenesis and glycogen synthesis. The overall GSD incidence is estimated 1 case per 20000-43000 live births. Read More

Sports Med 2006 ;36(12):1031-65

Laboratory of Exercise Biology BAPS EA 3533, Faculty of Sports Sciences, University of Blaise Pascal, Clermont-Ferrand, France.

Children are able to resist fatigue better than adults during one or several repeated high-intensity exercise bouts. This finding has been reported by measuring mechanical force or power output profiles during sustained isometric maximal contractions or repeated bouts of high-intensity dynamic exercises. The ability of children to better maintain performance during repeated high-intensity exercise bouts could be related to their lower level of fatigue during exercise and/or faster recovery following exercise. Read More

Semin Pediatr Neurol 2006 Jun;13(2):115-20

University Childrens' Hospital and Molecular Genetics and Metabolism Laboratory, Munich, Germany.

Glycogen storage diseases (GSDs) are characterized by abnormal inherited glycogen metabolism in the liver, muscle, and brain and divided into types 0 to X. GSD type I, glucose 6-phosphatase system, has types Ia, Ib, Ic, and Id, glucose 6-phosphatase, glucose 6-phosphate translocase, pyrophosphate translocase, and glucose translocase deficiencies, respectively. GSD type II is caused by defective lysosomal alpha-glucosidase (GAA), subdivided into 4 onset forms. Read More

J Inherit Metab Dis 2006 Apr-Jun;29(2-3):431-5

Paediatric Liver Service, King's College Hospital, Denmark Hill, London, SE5 9RS, UK.

Hepatocyte transplantation is being investigated as an alternative to orthotopic liver transplantation in patients with liver-based metabolic disorders. The progress made in this field to date is reviewed. Protocols have been developed using collagenase perfusion to isolate human hepatocytes from unused donor liver tissue. Read More

Haematologica 2006 May;91(5):652-5

Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI 53226, USA.

Erythrocyte membrane leakage of Ca2+ in familial phosphofructokinase deficiency results in a compensatory increase of Ca2+-ATPase activity that depletes ATP and leads to diminished erythrocyte deformability and a higher rate of hemolysis. Lowered ATP levels in circulating erythrocytes are accompanied by increased IMP, indicating that activated AMP deaminase plays a role in this metabolic dysregulation. Exposure to a calmodulin antagonist significantly slows IMP accumulation during experimental energy imbalance in patients' cells to levels that are similar to those in untreated controls, implying that Ca2+-calmodulin is involved in erythrocyte AMP deaminase activation in familial phosphofructokinase deficiency. Read More

Lakartidningen 2006 Mar 1-7;103(9):657-60

Norrlands universitetssjukhus, Umeå.

Nihon Rinsho 2004 Dec;62 Suppl 12:835-9

Department of Clinical Laboratory, Osaka Medical Center for Cancer and Cardiovascular Diseases.

Am J Respir Crit Care Med 2004 Jun 7;169(11):1238-44. Epub 2004 Apr 7.

Department of Medicine, Royal Victoria Hospital, Belfast, Northern Ireland.

During constant work-rate exercise above the lactic acidosis threshold, oxygen consumption fails to plateau by 3 minutes, but continues to rise slowly. This slow component correlates closely with the rise in lactate in normal subjects. We investigated if oxygen consumption during constant work-rate exercise could rise after 3 minutes in the absence of a rise in lactate. Read More

Neurology 2004 Jan;62(1):82-6

Neuromuscular Center, Institute for Exercise and Environmental Medicine of Presbyterian Hospital, Dallas, TX 75231, USA.

Objective: The spontaneous second wind in myophosphorylase deficiency (MD, McArdle's disease) represents a transition from low to a higher exercise capacity attributable to increased oxidation of blood-borne fuels, principally glucose and free fatty acids. Muscle phosphofructokinase deficiency (PFKD) blocks the metabolism of muscle glycogen and blood glucose. The authors inquired whether the additional restriction in glucose metabolism in PFKD prevents a spontaneous second wind. Read More

J Intern Med 2003 Dec;254(6):517-26

Department of Clinical Chemistry, University Hospital, Uppsala, Sweden.

The basis for life is the ability of the cell to maintain ion gradients across biological membranes. Such gradients are created by specific membrane-bound ion pumps [adenosine triphosphatases (ATPases)]. According to physicochemical rules passive forces equilibrate (dissipate) ion gradients. Read More

Pediatr Nephrol 2004 Jan 22;19(1):111-3. Epub 2003 Nov 22.

Département de Pédiatrie, Hôpital Edouard-Herriot, Université Claude-Bernard, Lyon, France.

A 16-year-old Caucasian girl was admitted to hospital with acute renal failure and hemolytic anemia due to rhabdomyolysis following a 3-km walk. (31)P-magnetic resonance spectroscopy provided characteristic spectra of type VII glycogen storage disease (phosphofructokinase deficiency). Read More

J Pediatr Gastroenterol Nutr 2003 Nov;37(5):566-70

Service d'Hématologie Biologique, Hôpital Antoine Béclère, Clamart, France.

Objectives: Glycogen storage disease type Ia (GSD-Ia), a congenital deficiency of hepatic glucose-6-phosphatase activity, is often associated with hyperproteinemia. To document the mechanism of hyperproteinemia, the proteins of the hemostatic system were analyzed according to their site of synthesis: hepatocyte, endothelial cell, or both. The role of inflammation was investigated by the measurement of tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) levels in plasma. Read More

Nihon Rinsho 2003 Jan;61 Suppl 1:307-12

Department of Basic Laboratory Medicine, School of Allied Health Science, Faculty of Medicine, Osaka University.

South Med J 2002 Dec;95(12):1436-40

Neurology Department, Neurological Hospital, Rosenhügel, Vienna, Austria.

Little is known about the progression of phosphofructokinase deficiency (glycogenosis type VII, Tarui's disease). We describe a 66-year-old woman who had this disease diagnosed in 1997. Initial manifestations had included simple partial seizures since 1977, anginal chest pain since 1982, and muscle cramps since 1983. Read More

South Med J 2002 Dec;95(12):1361-2

Nihon Naika Gakkai Zasshi 2002 Apr;91(4):1145-8

Curr Mol Med 2002 Mar;2(2):197-212

Department of Clinical Laboratory, Osaka Medical Center for Cancer and Cardiovascular Diseases, Japan.

Phosphofructokinase deficiency (Tarui disease, glycogen storage disease VII, GSD VII) stands out among all the GSDs. PFK deficiency was the first recognized disorder that directly affects glycolysis. Ever since the discovery of the disease in 1965, a wide range of biochemical, physiological and molecular studies of the disorder have greatly expanded our understanding of the function of normal muscle, general control of glycolysis and glycogen metabolism. Read More

Ryoikibetsu Shokogun Shirizu 2001 (36):28-34

Department of Basic Laboratory Science, School of Allied Health Science, Faculty of Medicine, Osaka University.

Eur J Pediatr 2001 Jul;160(7):452-3

Differential diagnosis of limb-girdle muscular dystrophy, including alpha-sarcoglycanopathy and Duchenne muscular dystrophy, is impossible to acheive on clinical grounds alone; therefore immunohistology, Western blotting and molecular genetic analysis are manadatory for a correct diagnosis. The patient's genotype with a hitherto unknown mutation (Tyr134STOP) in exon 5 adds to the growing spectrum of mutations in the alpha-sarcoglycan gene. Read More

J Small Anim Pract 2001 Jun;42(6):298-300

Dahlgaard's Dyreklinik, Birkerod, Denmark.

Phosphofructokinase (PFK) deficiency is an autosomal recessive inherited disorder in dogs causing haemolytic crises and exertional myopathy. The clinical signs may be confused with those of recurrent immune-mediated haemolytic anaemia. The deficiency has been commonly observed in field trial (working) English springer spaniels (ESSPs), but also in the conformation line of ESSPs in the USA over the past two decades. Read More

Neurology 2001 Jun;56(12):1739-45

National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Background: The authors previously reported the generation of a knockout mouse model of Pompe disease caused by the inherited deficiency of lysosomal acid alpha-glucosidase (GAA). The disorder in the knockout mice (GAA-/-) resembles the human disease closely, except that the clinical symptoms develop late relative to the lifespan of the animals. In an attempt to accelerate the course of the disease in the knockouts, the authors increased the level of cytoplasmic glycogen by overexpressing glycogen synthase (GSase) or GlutI glucose transporter. Read More

J Intern Med 2001 Jan;249(1):97-102

Department of Internal Medicine, Norrlands University Hospital, S-901 85 Umeå, Sweden.

Objectives: To establish by flow cytometry and fluorophores an increased calcium ion load in erythrocytes of four patients with Tarui's disease.

Design: Calcium ion levels were determined in erythrocytes of patients and controls under normal and energy-deprived conditions. Adenylates were measured to assess energy status of incubated erythrocytes. Read More

J Intern Med 2001 Jan;249(1):85-95

Department of Clinical Chemistry, University Hospital, S-751 85 Uppsala, Sweden.

Objectives: To critically evaluate whether an altered calcium homeostasis in erythrocytes could be contributing to the symptomatology of the Tarui's disease, which is an inherited phosphofructokinase (PFK) deficiency of the muscle isoenzyme. PFK is a tetrameric enzyme with three different isoenzymes, muscle (M), liver (L), and platelet (P). Erythrocytes contain a 50 : 50 hybrid of M and L type. Read More

Baillieres Best Pract Res Clin Haematol 2000 Mar;13(1):141-8

Department of Blood Transfusion Medicine, Tokyo Women's Medical University, Japan.

Phosphoglycerate kinase (PGK) deficiency is associated with hereditary haemolytic anaemia and often with central nervous system dysfunction and/or myopathy. Twenty-three families have been discovered with this condition. Nine have manifested both symptoms, six only haemolysis, and seven central nervous system dysfunction and/or myopathy without haemolysis; one case is asymptomatic. Read More

Semin Arthritis Rheum 2000 Jun;29(6):335-47

Department of Internal Medicine, Hospital Clínic, August Pi i Sunyer Biomedical Research Institute, Medical School, University of Barcelona, Catalonia, Spain.

Objectives: To investigate the clinical presentation, histological findings, and outcome of patients with congenital and metabolic myopathies (CM and MM) in whom the disease was diagnosed in childhood or adulthood.

Patients And Methods: We reviewed the diagnosis of all skeletal muscle biopsies performed by our group between 1984 and 1996 (13 years). All patients with CM and MM of childhood or adult onset were included in the study. Read More

Eur J Neurol 2000 Jan;7(1):111-3

Department of Neurology, University Hospital, Trondheim, Norway.

Phosphoglycerate kinase (PGK) catalyses the transfer of the acylphosphate group of 1,3-diphosphoglycerate to ADP with formation of 3-phosphoglycerate and ATP in the terminal stage of the glycolytic pathway. Two young brothers are presented who both experienced muscle pain, cramps and stiffness shortly after beginning heavy exercise. After these episodes they noticed that the urine was dark brown, indicating rhabdomyolysis and myoglobinuria. Read More

J Formos Med Assoc 1999 Mar;98(3):205-8

Department of Pediatrics, En Chu Kong Hospital, San-shia, Taiwan.

A 14-year-old girl had an acute episode of rhabdomyolysis after vigorous exercise and seizures. Laboratory studies revealed elevated creatine phosphokinase (CPK) activity and myoglobinuria without acute renal failure, as well as mild indirect hyperbilirubinemia, and hyperuricemia. The elevated CPK activity, mild indirect hyperbilirubinemia, and hyperuricemia persisted during a 10-month follow-up period, during which chronic hemolysis without overt anemia was also noted. Read More

Muscle Nerve 1999 May;22(5):621-7

Division of Geriatric Medicine, Medical College of Pennsylvania and Hahnemann University, Philadelphia, Pennsylvania 19131, USA.

Muscle-type phosphofructokinase (M-PFK) deficiency causes an exertional myopathy and chronic hemolysis in affected humans and dogs, the only animal model available. Deficient individuals have impaired glycolytic metabolism, impaired oxidative metabolism, and increased hemoglobin-oxygen (HbO2) affinity as a result of low 2,3-diphosphoglycerate (2,3-DPG) levels. The purpose of this study was to determine if PFK-deficient muscle has abnormal oxygen saturation during exercise. Read More

Neuromuscul Disord 1998 Oct;8(7):480-8

Department of Neurology, BG-Kliniken Bergmannsheil, Ruhr University Bochum, Germany.

Using 31P magnetic resonance spectroscopy, energy metabolism in calf muscles of two patients with biochemically and genetically proven muscular phosphofructokinase deficiency, and an asymptomatic heterozygote was monitored during isometric foot plantarflexion performed under aerobic and anaerobic conditions and in the aerobic recovery phases. In the heterozygote only a moderate alteration from normal was found in terms of an elevated ATP demand during exercise. In the homozygote, hexose phosphates, indicated as phosphomonoesters, increased dramatically during contraction. Read More

Ryoikibetsu Shokogun Shirizu 1998 (18 Pt 1):51-5

Second Department of Internal Medicine, Osaka University Medical School.