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J Clin Neuromuscul Dis 2022 Mar;23(3):162-164

Neuromuscular Division, Neurology Department, Tufts Medical Center, Boston, MA.

JHEP Rep 2021 Aug 30;3(4):100300. Epub 2021 Apr 30.

Gene Therapy Area, Foundation for Applied Medical Research, University of Navarra, IdisNA, Pamplona, Spain.

Gene therapy is becoming an increasingly valuable tool to treat many genetic diseases with no or limited treatment options. This is the case for hundreds of monogenic metabolic disorders of hepatic origin, for which liver transplantation remains the only cure. Furthermore, the liver contains 10-15% of the body's total blood volume, making it ideal for use as a factory to secrete proteins into the circulation. Read More

Mol Metab 2021 11 4;53:101265. Epub 2021 Jun 4.

Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. Electronic address:

Objective: Glycogen storage disease type 1a (GSD Ia) is a rare inherited metabolic disorder caused by mutations in the glucose-6-phosphatase (G6PC1) gene. When untreated, GSD Ia leads to severe fasting-induced hypoglycemia. Although current intensive dietary management aims to prevent hypoglycemia, patients still experience hypoglycemic events. Read More

Curr Opin Endocrinol Diabetes Obes 2020 10;27(5):283-290

Centre for Human Performance, Exercise and Rehabilitation, Brunel University, London, UK.

Purpose Of Review: To explore the potential of a low carbohydrate ketogenic diet (LCKD) to counter physical activity intolerance, pain and muscle damage for glycogen storage disease (GSD) V and VII, and highlight the realistic possibility that nutrition could be key.

Recent Findings: Carbohydrate (CHO) ingestion during physical activity in GSDV and a LCKD for GSDVII is common. For the latter, a long-term study demonstrated improvement in physiological markers while on a LCKD. Read More

Sci Rep 2020 05 29;10(1):8765. Epub 2020 May 29.

Department of Sport Medicine and Functional Explorations-CRNH Auvergne, Clermont-Ferrand University Hospital, G. Montpied Hospital, Clermont-Ferrand, F-63000, France.

Metabolic myopathies are muscle disorders caused by a biochemical defect of the skeletal muscle energy system resulting in exercise intolerance. The primary aim of this research was to evaluate the oxygen cost (∆V'O/∆Work-Rate) during incremental exercise in patients with metabolic myopathies as compared with patients with non-metabolic myalgia and healthy subjects. The study groups consisted of eight patients with muscle glycogenoses (one Tarui and seven McArdle diseases), seven patients with a complete and twenty-two patients with a partial myoadenylate deaminase (MAD) deficiency in muscle biopsy, five patients with a respiratory chain deficiency, seventy-three patients with exercise intolerance and normal muscle biopsy (non-metabolic myalgia), and twenty-eight healthy controls. Read More

Front Neurol 2020 4;11:57. Epub 2020 Feb 4.

Unit of Clinical Physiology, HUS Medical Imaging Center, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.

A deficiency of muscle phosphofructokinase (PFKM) causes a rare metabolic muscle disease, the Tarui disease (Glycogen storage disease type VII, GSD VII) characterized by exercise intolerance with myalgia due to an inability to use glucose as an energy resource. No medical treatment for GSD VII currently exists. The aim of this study was to determine whether a dietary intervention with excessive fat intake would benefit GSD VII. Read More

Virchows Arch 2019 Dec 30;475(6):671-686. Epub 2019 Jul 30.

Neuromuscular Department, Fondazione San Camillo Hospital IRCCS, Lido Venice, Italy.

An abnormal structural form of glycogen (with less branching points or amylopectin-like polysaccharide) called polyglucosan (PG) may accumulate in various tissues such as striated and smooth muscles, brain, nerve, liver and skin, and cause a group of nine different genetic disorders manifesting with a variety of clinical phenotypes that affect mainly the nervous system (Lafora disease, adult PG body disease), the heart (glycogen storage disease type XV, hypertrophic cardiomyopathy type 6, PG body myopathy type 1) and the skeletal muscle (glycogen storage disease type IV, glycogen storage disease type VII, PG body myopathy type 2), depending on the organs which are mostly affected by the PG aggregates. The pathological feature of PG storage in tissues is a hallmark of these disorders. Whole-genome sequencing has allowed to obtain a diagnosis in a large number of patients with a previously unrecognized disorder. Read More

Hastings Cent Rep 2018 Jul;48 Suppl 2:S32-S34

I attended the NSIGHT Ethics and Policy Advisory Board's meeting on sequencing newborns as a research associate in a joint apprenticeship between the University of California, San Francisco, Institute for Human Genetics and the university's Program in Bioethics. But I also came to the meeting with a deeply personal perspective: I had spent nearly my entire childhood in search of a diagnosis and therefore was eager to hear the board's discussion on how to ethically include genomic sequencing early in life. Genomic sequencing in the newborn period could have helped me avoid my diagnostic odyssey by revealing the cause of my condition shortly after birth. Read More

Continuum (Minneap Minn) 2016 Dec;22(6, Muscle and Neuromuscular Junction Disorders):1829-1851

Purpose Of Review: Metabolic myopathies are genetic disorders that impair intermediary metabolism in skeletal muscle. Impairments in glycolysis/glycogenolysis (glycogen-storage disease), fatty acid transport and oxidation (fatty acid oxidation defects), and the mitochondrial respiratory chain (mitochondrial myopathies) represent the majority of known defects. The purpose of this review is to develop a diagnostic and treatment algorithm for the metabolic myopathies. Read More

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