関: McArdle disease、McArdle's disease、muscle phosphorylase deficiency、type V glycogen storage disease

WordNet

write by means of a keyboard with types; "type the acceptance letter, please" (同)typewrite
a small metal block bearing a raised character on one end; produces a printed character when inked and pressed on paper; "he dropped a case of type, so they made him pick them up"
(biology) the taxonomic group whose characteristics are used to define the next higher taxon
a subdivision of a particular kind of thing; "what type of sculpture do you prefer?"
all of the tokens of the same symbol; "the word `element contains five different types of character"
printed characters; "small type is hard to read"
identify as belonging to a certain type; "Such people can practically be typed" (同)typecast
an impairment of health or a condition of abnormal functioning
(computer science) the process of storing information in a computer memory or on a magnetic tape or disk
the act of storing something
the commercial enterprise of storing goods and materials
caused by or altered by or manifesting disease or pathology; "diseased tonsils"; "a morbid growth"; "pathologic tissue"; "pathological bodily processes" (同)morbid, pathologic, pathological
one form in which body fuel is stored; stored primarily in the liver and broken down into glucose when needed by the body (同)animal_starch

PrepTutorEJDIC

〈C〉(…の)『型』,タイプ,類型,種類(kind)《+of+名》 / 〈C〉(その種類の特質を最もよく表している)『典型』,手本,模範《+of+名》 / 〈U〉《集合的に》活字;〈C〉(1個の)活字 / 〈U〉(印刷された)字体,活字 / 〈C〉(貨幣・メダルなどの)模様,図柄 / 〈C〉血液型(blood group) / …‘を'タイプに打つ / (…として)…‘を'分類する《+名+as+名(doing)》 / …‘の'型を決める / タイプライターを打つ
(体の)『病気』,疾患 / (精神・道徳などの)病気,病弊
女性の話術芸人 =diseur
(倉庫などに)貯蔵すること,保管 / 貯蔵所,倉庫 / 保管料
病気にかかった / 病的な,不健全な(morbid)
グリコーゲン,糖原

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/11/24 05:01:01」(JST)

wiki en

Glycogen storage disease type V (GSD-V) is a metabolic disorder, more specifically a glycogen storage disease, caused by a deficiency of myophosphorylase.^[1] Its incidence is reported as 1 in 100,000,^[2] approximately the same as glycogen storage disease type I.

GSD type V is also known as McArdle disease or muscle phosphorylase (myophosphorylase) deficiency. The disease was first reported in 1951 by Dr. Brian McArdle of Guy's Hospital, London.^[3]

History

The deficiency was the first metabolic myopathy to be recognized, when Dr. McArdle described the first case in a 30-year-old man who always experienced pain and weakness after exercise. Dr. McArdle noticed this patient’s cramps were electrically silent and his venous lactate levels failed to increase upon ischemic exercise. (The ischemic exercise consists of the patient squeezing a hand dynamometer at maximal strength for a specific period of time, usually a minute, with a blood pressure cuff, which is placed on the upper arm and set at 250 mmHg, blocking blood flow to the exercising arm.) Notably, this is the same phenomenon that occurs when muscle is poisoned by iodoacetate, a substance that blocks breakdown of glycogen into glucose and prevents the formation of lactate. Dr. McArdle accurately concluded that the patient had a disorder of glycogen breakdown that specifically affected skeletal muscle. The associated enzyme deficiency was discovered in 1959 by W. F. H. M. Mommaerts et al.^[4]

Signs and symptoms

The onset of this disease is usually noticed in childhood,^[5] but often not diagnosed until the third or fourth decade of life. Symptoms include exercise intolerance with muscle pain, early fatigue, painful cramps, and myoglobin in the urine (often provoked by a bout of exercise). Myoglobinuria may result from the breakdown of skeletal muscle known as rhabdomyolysis, a condition in which muscle cells breakdown, sending their contents into the bloodstream.

Patients may exhibit a “second wind” phenomenon. This is characterized by the patient’s better tolerance for aerobic exercise such as walking and cycling after approximately 10 minutes.^[6] This is attributed to the combination of increased blood flow and the ability of the body to find alternative sources of energy, like fatty acids and proteins. In the long term, patients may exhibit renal failure due to the myoglobinuria, and with age, patients may exhibit progressively increasing weakness and substantial muscle loss.

Patients may present at emergency rooms with severe fixed contractures of the muscles and often severe pain. These require urgent assessment for rhabdomyolysis as in about 30% of cases this leads to acute renal failure. Left untreated this can be life-threatening. In a small number of cases compartment syndrome has developed, requiring prompt surgical referral.

Diagnosis

There are some laboratory tests that may aid in diagnosis of GSD-V. A muscle biopsy will note the absence of myophosphorylase in muscle fibers. In some cases, acid-Schiff stained glycogen can be seen with microscopy.

Genetic sequencing of the PYGM gene (which codes for the muscle isoform of glycogen phosphorylase^[7]^[8]) may be done to determine the presence of gene mutations, determining if McArdle's is present. This type of testing is considerably less invasive than a muscle biopsy. The test involves bidirectional sequencing of the coding regions of all 20 PYGM exons plus about 50 Bp of non-coding flanking DNA on each side. Because the disease consists of two gene mutations and because the test can be performed to identify carries of the disease, the test has two tiers. Tier 1 involves sequencing of exons 1 and 5. If two likely causative mutations are detected in patients in Tier 1 or one mutation carriers in Tier 1, then the testing stops. Otherwise, testing continues with Tier 2 involving sequencing the remaining 18 exons. These tests require a simple blood draw.^[9]

The physician can also perform an ischemic forearm exercise test as described above. Some findings suggest a nonischemic test could be performed with similar results.^[10] The nonischemic version of this test would involve not cutting off the blood flow to the exercising arm. Findings consistent with McArdle’s disease would include a failure of lactate in venous blood and exaggerated ammonia levels. These findings would indicate a severe muscle glycolytic block. Ammonia arises from the impaired buffering of ADP, which leads to an increase in AMP concentration resulting in an increase in AMP deamination.

Physicians may also check resting levels of creatine kinase, which are moderately increased in 90% of patients. In some, the level is increased by multitudes - a person without GSD-V will have a CK between 60 and 400IU/L, while a person with the syndrome may have a level of 5,000 IU/L at rest, and may increase to 35,000 IU/L or more with muscle exertion. This can help distinguish McArdle's syndrome from carnitine palmitoyltransferase II deficiency (CPT-II), a lipid-based metabolic disorder which prevents fatty acids from being transported into mitochondria for use as an energy source. Also, serum electrolytes and endocrine studies (such as thyroid function, parathyroid function and growth hormone levels) will also be completed. Urine studies are required only if rhabdomyolysis is suspected. Urine volume, urine sediment and myoglobin levels would be ascertained. If rhabdomyolysis is suspected, serum myoglobin, creatine kinase, lactate dehydrogenase, electrolytes and renal function will be checked.

Treatment

Supervised exercise programs have been shown in small studies to improve exercise capacity by several measures.^[11]^[12]

Oral sucrose treatment (for example a sports drink with 75 grams of sucrose in 660 ml.) taken 30 minutes prior to exercise has been shown to help improve exercise tolerance including a lower heart rate and lower perceived level of exertion compared with placebo.^[13]

Genetics

There are two autosomal recessive forms of this disease, childhood-onset and adult-onset. The gene for myophosphorylase, PYGM (the muscle-type of the glycogen phosphorylase gene), is located on chromosome 11q13. According to the most recent publications, 95 different mutations have been reported. The forms of the mutations may vary between ethnic groups. For example, the R49X (Arg49Stop) mutation is most common in North America and western Europe, and the Y84X mutation is most common among central Europeans.

The exact method of protein disruption has been elucidated in certain mutations. For example, R138W is known to disrupt to pyridoxal phosphate binding site.^[14] In 2006, another mutation (c.13_14delCT) was discovered which may contribute to increased symptoms in addition to the common Arg50Stop mutation.^[15]

Pathophysiology

Myophosphorylase is involved in the breakdown of glycogen to glucose for use in muscle. The enzyme removes 1,4 glycosyl residues from outer branches of glycogen and adds inorganic phosphate to form glucose-1-phosphate. Cells form glucose-1-phosphate instead of glucose during glycogen breakdown because the polar, phosphorylated glucose cannot leave the cell membrane and so is marked for intracellular catabolism.

Myophosphorylase exists in the active form when phosphorylated. The enzyme phosphorylase kinase plays a role in phosphorylating glycogen phosphorylase to activate it and another enzyme, protein phosphatase-1, inactivates glycogen phosphorylase through dephosphorylation.

Myophosphorylase

Structure

The myophosphorylase structure consists of 842 amino acids. Its molecular weight of the unprocessed precursor is 97 kDa. The 3D structure has been determined of this protein. The interactions of several amino acids in myophosphorylase’s structure are known. Ser-14 is modified by phosphorylase kinase during activation of the enzyme. Lys-680 is involved in binding the pyridoxal phosphate, which is the active form of vitamin B₆, a cofactor required by myophosphorylase. By similarity other sites have been estimated: Tyr-76 binds AMP, Cys-109 and Cys-143 are involved in subunit association, and Tyr-156 may be involved in allosteric control.

Function

Myophosphorylase is the form of the glycogen phosphorylase found in muscle. (see The Reaction above). Failure of this enzyme ultimately impairs the operation of ATPases. This is due to the lack of normal pH fall during exercise, which impairs the creatine kinase equilibrium and exaggerates the rise of ADP.

References

^ Rubio JC, Garcia-Consuegra I, Nogales-Gadea G, et al. (2007). "A proposed molecular diagnostic flowchart for myophosphorylase deficiency (McArdle disease) in blood samples from Spanish patients". Hum. Mutat. 28 (2): 203–4. doi:10.1002/humu.9474. PMID 17221871.
^ http://mcardlesdisease.org/
^ Brian McArdle at Who Named It?
^ Mommaerts, W. F. H. M; Illingworth, Barbara; Pearson, Carl M.; Guillory, R. J.; Seraydarian, K. (22 April 1959). "A Functional Disorder of Muscle Associated with the Absence of Phosphorylase". Proceedings of the National Academy of Sciences. 45: 791–797. doi:10.1073/pnas.45.6.791. Retrieved 29 March 2015.
^ Wolfe GI, Baker NS, Haller RG, Burns DK, Barohn RJ (2000). "McArdle's disease presenting with asymmetric, late-onset arm weakness". Muscle Nerve. 23 (4): 641–5. doi:10.1002/(SICI)1097-4598(200004)23:4<641::AID-MUS25>3.0.CO;2-M. PMID 10716777.
^ Pearson CM, Rimer DG, Mommaerts WF (April 1961). "A metabolic myopathy due to absence of muscle phosphorylase". Am. J. Med. 30: 502–17. doi:10.1016/0002-9343(61)90075-4. PMID 13733779.
^ NCBI Gene ID 5837: PYGM phosphorylase, glycogen, muscle, retrieved 22 May 2013
^ "PYGM", NLM Genetics Home Reference, retrieved 22 May 2013
^ Glycogen Storage Disease, Type V (McArdle Disease) via PYGM Gene Sequencig Check |archiveurl= value (help) (PDF), Prevention Genetics, March 30, 2011, archived from the original (PDF) on March 23, 2012, retrieved 22 May 2013
^ Kazemi-Esfarjani P, Skomorowska E, Jensen TD, Haller RG, Vissing J (2002). "A nonischemic forearm exercise test for McArdle disease". Ann. Neurol. 52 (2): 153–9. doi:10.1002/ana.10263. PMID 12210784.
^ Pérez M, Moran M, Cardona C, et al. (January 2007). "Can patients with McArdle's disease run?". Br J Sports Med. 41 (1): 53–4. doi:10.1136/bjsm.2006.030791. PMC 2465149. PMID 17000713.
^ Haller, Ronald G.; Wyrick, Phil; Taivassalo, Tanja; Vissing, John (2006-06-01). "Aerobic conditioning: An effective therapy in McArdle's disease". Annals of Neurology. 59 (6): 922–928. doi:10.1002/ana.20881. ISSN 1531-8249.
^ Vissing, John; Haller, Ronald G. (2003-12-25). "The Effect of Oral Sucrose on Exercise Tolerance in Patients with McArdle's Disease". New England Journal of Medicine. 349 (26): 2503–2509. doi:10.1056/NEJMoa031836. ISSN 0028-4793. PMID 14695410.
^ Martín MA, Rubio JC, Wevers RA, et al. (2004). "Molecular analysis of myophosphorylase deficiency in Dutch patients with McArdle's disease". Ann. Hum. Genet. 68 (Pt 1): 17–22. doi:10.1046/j.1529-8817.2003.00067.x. PMID 14748827.
^ Rubio, JC; et al. (August 1996). "Novel mutation in the PYGM gene resulting in McArdle disease.". Arch Neurol. 63 (12): 1782–4. doi:10.1001/archneur.63.12.1782. PMID 17172620.

External links

The Association for Glycogen Storage Disease
The Association for Glycogen Storage Disease (UK) McArdle information
McArdle Disease Emergencies - AGSD (UK)
Information About McArdle's Disease
GeneReview/NIH/UW entry on Glycogen Storage Disease Type V
Asociación Española de Enfermos de Glucogenosis
Videos of advice and information for patients on how to manage their McArdle Disease, from the UK support group (see above).
Euromac, a EU funded consortium of medical and research institutes across Europe which is building a patient registry and raising standards of care for people with McArdle Disease.

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 筋ホスホリラーゼ欠損症（糖原病V型、マッカードル病） myophosphorylase deficiency glycogen storage disease v mcardle disease
2. グルコースおよびグリコーゲン代謝の遺伝性疾患の概要 overview of inherited disorders of glucose and glycogen metabolism
3. 横紋筋融解症の原因 causes of rhabdomyolysis
4. 神経筋疾患の評価における筋酵素 muscle enzymes in the evaluation of neuromuscular diseases
5. Lysosomal acid alpha-glucosidase deficiency (Pompe disease, glycogen storage disease II, acid maltase deficiency)

English Journal

Clinical and Molecular Characterization of Mcardle's Disease in Brazilian Patients.

Gurgel-Giannetti J, Nogales-Gadea G, van der Linden H Jr, Bellard TM, Brasileiro Filho G, Giannetti AV, de Castro Concentino EL, Vainzof M.SourceDepartment of Pediatrics, Pediatric Neurology Service, Medical School, Universidade Federal de Minas Gerais, Rua Santa Catarina, 1042 apt: 201, Belo Horizonte, MG, Brazil, gurgelju@yahoo.com.br.
Neuromolecular medicine.Neuromolecular Med.2013 Sep;15(3):470-5. doi: 10.1007/s12017-013-8233-2. Epub 2013 May 8.
McArdle's disease, a glycogen storage disease type V, is caused by a deficiency of the enzyme myophosphorylase, encoded by the PYGM gene. Worldwide distribution of mutations has revealed interesting data about the prevalence of mutations and population migrations. Currently, more than 100 mutations
PMID 23653251

McArdle's disease (glycogen storage disease type V) and anesthesia - a case report and review of the literature.

Bollig G.SourceDepartment of Anesthesiology and Intensive Care, Palliative Medicine and Pain Therapy, HELIOS Klinikum Schleswig, Schleswig, Germany; Department of Surgical Sciences, Haukeland University Hospital, University of Bergen, Bergen, Norway.
Paediatric anaesthesia.Paediatr Anaesth.2013 Sep;23(9):817-23. doi: 10.1111/pan.12164. Epub 2013 Apr 9.
McArdles disease (glycogen storage disease type v) is a rare condition in which energy-metabolism in the muscle is hampered. A case report is presented and the possible risk for perioperative complications including malignant hyperthermia is discussed. A checklist for the anesthesiological managemen
PMID 23565573

Monocarboxylate transporters and mitochondrial creatine kinase protein content in McArdle disease.

Kitaoka Y, Ogborn DI, Mocellin NJ, Schlattner U, Tarnopolsky MA.SourceDepartment of Pediatrics, McMaster University, 1200 Main Street West, Hamilton, Ontario, Canada L8N 3Z5. kitaoka@mcmaster.ca
Molecular genetics and metabolism.Mol Genet Metab.2013 Apr;108(4):259-62. doi: 10.1016/j.ymgme.2013.01.005. Epub 2013 Jan 19.
McArdle disease (MD) is a metabolic myopathy due to myophosphorylase deficiency. We examined monocarboxylate transporters (MCT) and creatine kinase (CK) protein content in skeletal muscle from MD patients and age-matched controls to evaluate potential cellular adaptations that compensate for the los
PMID 23434346

Japanese Journal

Molecular and biochemical characterization of Tunisian patients with glycogen storage disease type III : This article has been corrected since advance Online Publication, and a corrigendum is also printed in this issue

Mili Amira,Charfeddine Ilhem Ben,Mamai Ons [他],CHERIF Wafa,ADALA Labiba,AMARA Abdelbasset,PAGLIARANI Serena,LUCCHIARI Sabrina,AYADI Abdelkarim,TEBIB Neji,HARBI Abdelaziz,BOUGUILA Jihene,H'MIDA Dorra,SAAD Ali,LIMEM Khalifa,COMI GP,GRIBAA Moez
Journal of human genetics 57(3), 170-175, 2012-03-01
NAID 10030711965

糖原病Ib型患児に対する口蓋形成術の全身麻酔経験

小島好博,小林義和,大上沙央理,山田守正,水谷英樹,竹田清
日本歯科麻酔学会雑誌 40(1), 50-51, 2012-01-15
NAID 10030283368

Discussion Regarding the Method of Screening for Hepatocellular Carcinoma in Glycogen Storage Disease Type 1a

Ochi Hironori,Hiraoka Atsushi,Michitaka Kojiro
Internal Medicine 51(13), 1813-1813, 2012
NAID 130002062211

Related Pictures

★リンクテーブル★

リンク元	「マッカードル病」「5型糖原貯蔵障害」「type V glycogen storage disease」
拡張検索	「glycogen storage disease type VII」「glycogen storage disease type VI」「glycogen storage disease type VIII」
関連記事	「disease」「type」「storage」「Vd」「V」

「マッカードル病」

Glycogen storage disease type V
	Muscle biopsy specimen showing vacuolar myopathy. The patient had a type V glycogenosis (McArdle Disease)
Classification and external resources
Specialty	endocrinology
ICD-10	E74.0
ICD-9-CM	271.0
OMIM	232600
DiseasesDB	5307
MedlinePlus	000329
eMedicine	med/911
MeSH	D006012
GeneReviews	Glycogen Storage Disease Type V;
	[edit on Wikidata]