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==Overview==
==Overview==


'''Glycogen storage disease''' (synonyms: '''glycogenosis''', '''dextrinosis''') is any one of several [[inborn error of metabolism|inborn errors of metabolism]] that result from [[enzyme]] defects that affect the processing of [[glycogen]] synthesis or breakdown within [[muscle]]s, [[liver]], and other cell types.
== Pathophysiology of Oral Cancer ==


== Types ==
=== Tumor suppressor genes (TSGs) ===
* It is understood that oral cavity cancer is the result of allelic imbalance which is caused by chromosomal changes particularly in chromosome 3,9,11 and 17.
* These changes lead to mutation in tumor suppressor genes (TSGs).
* Normally TSGs modulate normal growth.
* Mutation of these TSGs leads to dysfunctional growth control.
* Mutation most commonly occurs in either of the following:
** Short arm of chromosome 3
** TSG termed ''P16'' on chromosome 9
** TSG termed ''TP53'' on chromosome 17
* Cytochrome P450 genotypes is related to mutations in some TSGs  and lead to oral squamous cell carcinoma.
* In western countries (eg, United Kingdom, United States, Australia) ''TP53'' [[Mutation|mutations]] are the most common molecular change that leads to oral [[squamous cell carcinoma]].


There are eleven (11) distinct diseases that are commonly considered to be glycogen storage diseases (some previously thought to be distinct have been reclassified). (Although [[glycogen synthase]] deficiency does not result in storage of extra glycogen in the liver, it is often classified with the GSDs as type 0 because it is another defect of glycogen storage and can cause similar problems.)
=== Oncogenes ===
* Cancer may also occur if there is mutation to other genes that control cell growth, mainly oncogenes.
* Oncogenes most commonly involved are:
** Chromosome 11 (''PRAD1)''
** Chromosome 17 (Harvey ras [H-''ras''])
* In eastern countries (eg, India, Southeast Asia), ''ras'' [[oncogenes]] is a more common cause of oral squamous cell carcinoma.  


* GSD type VIII: In the past, considered a distinct condition.<ref name="pmid4508182">{{cite journal |author=Ludwig M, Wolfson S, Rennert O |title=Glycogen storage disease, type 8 |journal=Arch. Dis. Child. |volume=47 |issue=255 |pages=830–3 |year=1972 |month=October |pmid=4508182 |pmc=1648209 |doi= 10.1136/adc.47.255.830|url=}}</ref> Now classified with VI.<ref name="urleMedicine - Glycogen-Storage Disease Type VI : Article by Lynne Ierardi-Curto">{{cite web |url=http://www.emedicine.com/ped/TOPIC2564.HTM |title=eMedicine - Glycogen-Storage Disease Type VI : Article by Lynne Ierardi-Curto |format= |work= |accessdate=}}</ref> Has been described as [[X-linked recessive]].<ref name="urlDefinition: glycogen storage disease type VIII from Online Medical Dictionary">{{cite web |url=http://cancerweb.ncl.ac.uk/cgi-bin/omd?glycogen+storage+disease+type+VIII |title=Definition: glycogen storage disease type VIII from Online Medical Dictionary |format= |work= |accessdate=}}</ref>
=== Carcinogen-metabolizing enzymes ===
* Carcinogen-metabolizing enzymes are known to cause cancer in some patients.
* Cytotoxic enzymes such as alcohol dehydrogenase result in the production of:
** Free radicles
** DNA hydroxylated bases
* These cytotoxic enzymes especially predispose oral squamous cell carcinoma.


* GSD type X: In the past, considered a distinct condition.<ref name="pmid6940112">{{cite journal |author=Warren MF, Hamilton PB |title=Glycogen storage disease type X caused by ochratoxin A in broiler chickens |journal=Poult. Sci. |volume=60 |issue=1 |pages=120–3 |year=1981 |month=January |pmid=6940112 |doi= |url=}}</ref><ref name="pmid760630">{{cite journal |author=Huff WE, Doerr JA, Hamilton PB |title=Decreased glycogen mobilization during ochratoxicosis in broiler chickens |journal=Appl. Environ. Microbiol. |volume=37 |issue=1 |pages=122–6 |year=1979 |month=January |pmid=760630 |pmc=243410 |doi= |url=http://aem.asm.org/cgi/pmidlookup?view=long&pmid=760630}}</ref> Now classified with VI.<ref name="urleMedicine - Glycogen-Storage Disease Type VI : Article by Lynne Ierardi-Curto">{{cite web |url=http://www.emedicine.com/ped/TOPIC2564.HTM |title=eMedicine - Glycogen-Storage Disease Type VI : Article by Lynne Ierardi-Curto |format= |work= |accessdate=}}</ref>
=== Alcohol ===


{|class="wikitable" class="sortable wikitable"
Carcinogen-metabolizing enzymes are implicated in some patients. Alcohol dehydrogenase oxidizes ethanol to acetaldehyde, which is cytotoxic and results in the production of free radicals and DNA hydroxylated bases; alcohol dehydrogenase type 3 genotypes appear predisposed to OSCC. Cytochrome P450 can activate many environmental procarcinogens. Ethanol is also metabolized to some extent by cytochrome P450 IIEI (CYP2E1) to acetaldehyde. Mutations in some TSGs may be related to cytochrome P450 genotypes and predispose to OSCC. Glutathione S transferase (GST) genotypes may have impaired activity; for example, the null genotype of GSTM1 has a decreased capacity to detoxify tobacco carcinogens. Some GSTM1 and GSTP1 polymorphic genotypes and GSTM1 and GSTT1 null genotypes have been shown to predispose to OSCC. ''N''-acetyltransferases NAT1 and NAT2 acetylate procarcinogens. ''N''-acetyl transferase NAT1*10 genotypes may be a genetic determinant of OSCC, at least in some populations.
| '''Number''' || '''Enzyme deficiency''' || '''Eponym''' || '''Incidence''' || '''[[Hypoglycemia|Hypo-<br>glycemia]]?''' || '''[[Hepatomegaly|Hepato-<br>megaly]]?''' || '''[[Hyperlipidemia|Hyperlip-<br>idemia]]?''' || '''Muscle symptoms''' || '''Development/ prognosis''' || '''Other symptoms'''
|-
| [[Glycogen storage disease type I|GSD type I]] || [[glucose-6-phosphatase]] || [[von Gierke's disease]] || 1 in 50,000<ref name=Roth/>- 100,000<ref>[http://www.agsdus.org/html/typeivongierke.htm The Association for Glycogen Storage Disease > Type I Glycogen Storage Disease Type I GSD] This page was created in October 2006.</ref> births || Yes || Yes || Yes || None || [[Growth failure]] || [[Lactic acidosis]], [[hyperuricemia]]
|-
| [[Glycogen storage disease type II|GSD type II]] || [[acid maltase]] || [[Pompe's disease]] || 1 in 60,000- 140,000 births<ref name=Ausems/> || No || Yes || No || [[Muscle weakness]] || *Death by age ~2 years (infantile variant) || [[heart failure]]
|-
| [[Glycogen storage disease type III|GSD type III]]  || [[glycogen debrancher]] || [[Cori's disease]] or [[Forbes' disease]] || 1 in 100,000 births || Yes ||  Yes || Yes || [[Myopathy]] || ||
|-
| [[Glycogen storage disease type IV|GSD type IV]]  || [[glycogen branching enzyme]] || [[Andersen disease]] || || No ||  Yes,<br> also <br> [[cirrhosis]] || No || None || [[Failure to thrive]], death at age ~5 years ||
|-
| [[Glycogen storage disease type V|GSD type V]]  || [[muscle glycogen phosphorylase]] || [[McArdle disease]] || 1 in 100,000<ref>http://mcardlesdisease.org/</ref> || No ||  No || No ||Exercise-induced cramps, [[Rhabdomyolysis]] || || [[Renal failure]] by [[myoglobinuria]]
|-
| [[Glycogen storage disease type VI|GSD type VI]]  || [[liver glycogen phosphorylase]] || [[Hers' disease]] || 1 in 65,000- 85,000 births<ref name=Ierardi-Curto>[http://emedicine.medscape.com/article/950587-overview eMedicine Specialties > Pediatrics: Genetics and Metabolic Disease > Metabolic Diseases > Glycogen-Storage Disease Type VI] Author: Lynne Ierardi-Curto, MD, PhD. Updated: Aug 4, 2008</ref> || Yes ||  Yes|| No ||None || ||
|-
| [[Glycogen storage disease type VII|GSD type VII]]  || [[phosphofructokinase 1|muscle phosphofructokinase]] || [[Tarui's disease]] ||  ||  No ||  No || No ||Exercise-induced muscle cramps and weakness || [[growth retardation]] || [[Haemolytic anaemia]]
|-
| [[Glycogen storage disease type IX|GSD type IX]]  || [[phosphorylase kinase]], [[PHKA2]] || -  || || Yes ||  No || Yes || None || [[Delayed motor development]], [[Growth retardation]] ||
|-
| [[Glycogen storage disease type XI|GSD type XI]]  || [[glucose transporter]], [[GLUT2]] || [[Fanconi-Bickel syndrome]] || || Yes ||  Yes || No || None || ||
|-
| [[Glycogen storage disease type XII|GSD type XII]]  || [[Aldolase A]] || [[Red cell aldolase deficiency]] ||  || ? || ? || ? || [[Exercise intolerance]], [[cramps]] || ||
|-
| [[Glycogen storage disease type XIII|GSD type XIII]]  || [[enolase|β-enolase]] || - ||  || ? || ? || ? || [[Exercise intolerance]], [[cramps]] || Increasing intensity of [[myalgia|myalgias]] over decades<ref name="Httpneuromuscularwustledumsysglycogenhtmlenolase">http://neuromuscular.wustl.edu/msys/glycogen.html#enolase</ref> || [[Creatine kinase|Serum CK]]: Episodic elevations; Reduced with rest<ref name="Httpneuromuscularwustledumsysglycogenhtmlenolase" /> ||
|-
| [[Glycogen storage disease type 0|GSD type 0]]  || [[glycogen synthase]]  || - ||  || Yes ||  No || No || Occasional [[muscle cramp]]ing || ||
|}


==Gross Pathological Findings==
Tobacco is a potent risk factor for oral cancer. An interaction occurs between redox-active metals in saliva and the low reactive free radicals in cigarette smoke. The result may be that saliva loses its antioxidant capacity and instead becomes a potent pro-oxidant milieu.<sup> [[null 5]]</sup>


Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission. [http://www.peir.net © PEIR, University of Alabama at Birmingham, Department of Pathology]
DNA repair genes are clearly involved in the pathogenesis of some rare cancers, such as those that occur in association with xeroderma pigmentosum, but, more recently, evidence of defective DNA repair has also been found to underlie some OSCCs.


<div align="left">
An immune deficiency state may predispose one to a higher risk of developing OSCC, especially lip cancer.
<gallery heights="175" widths="175">
Image:218243.jpg|Pompe's Disease, Glycogen Storage Disease Type II. Child in crib
Image:227286.jpg|Pompe's Disease, Glycogen Storage Disease Type II
Image:227289.jpg|Pompe's Disease, Glycogen Storage Disease Type II
</gallery>
</div>


==Gross Pathological Findings==


<div align="left">
Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission. [http://www.peir.net © PEIR, University of Alabama at Birmingham, Department of Pathology]
<gallery heights="175" widths="175">
Image:227292.jpg|Pompe's Disease, Glycogen Storage Disease Type II, 9 years old patient
Image:227295.jpg|Pompe's Disease, Glycogen Storage Disease Type II, 9 years old patient
</gallery>
</div>
 
 
<div align="left">
<gallery heights="175" widths="175">
Image:227298.jpg|Pompe's Disease, Glycogen Storage Disease Type II
Image:227313.jpg|Pompe's Disease, Glycogen Storage Disease Type II
</gallery>
</div>
 
==Microscopic Pathological Findings==


Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission. [http://www.peir.net © PEIR, University of Alabama at Birmingham, Department of Pathology]
<div align="left"></div>


<div align="left">
<div align="left"></div>
<gallery heights="175" widths="175">
Image:214344.jpg|Muscle: Glycogen Storage Disease
Image:214346.jpg|Muscle: Glycogen Storage Disease
Image:237571.jpg|Nerve: Glycogen Storage Disease Macrophages; Longitudinal Section of Peripheral Nerve
</gallery>
</div>


==Heart & Liver in Glycogen Storage Disease==
<div align="left"></div>


{{#ev:youtube|inSkXkNK_dE}}
{{#ev:youtube|inSkXkNK_dE}}

Revision as of 16:31, 2 February 2018


Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sargun Singh Walia M.B.B.S.[2]

Overview

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [3]; Associate Editor(s)-in-Chief:

Overview

Pathophysiology of Oral Cancer

Tumor suppressor genes (TSGs)

  • It is understood that oral cavity cancer is the result of allelic imbalance which is caused by chromosomal changes particularly in chromosome 3,9,11 and 17.
  • These changes lead to mutation in tumor suppressor genes (TSGs).
  • Normally TSGs modulate normal growth.
  • Mutation of these TSGs leads to dysfunctional growth control.
  • Mutation most commonly occurs in either of the following:
    • Short arm of chromosome 3
    • TSG termed P16 on chromosome 9
    • TSG termed TP53 on chromosome 17
  • Cytochrome P450 genotypes is related to mutations in some TSGs and lead to oral squamous cell carcinoma.
  • In western countries (eg, United Kingdom, United States, Australia) TP53 mutations are the most common molecular change that leads to oral squamous cell carcinoma.

Oncogenes

  • Cancer may also occur if there is mutation to other genes that control cell growth, mainly oncogenes.
  • Oncogenes most commonly involved are:
    • Chromosome 11 (PRAD1)
    • Chromosome 17 (Harvey ras [H-ras])
  • In eastern countries (eg, India, Southeast Asia), ras oncogenes is a more common cause of oral squamous cell carcinoma.

Carcinogen-metabolizing enzymes

  • Carcinogen-metabolizing enzymes are known to cause cancer in some patients.
  • Cytotoxic enzymes such as alcohol dehydrogenase result in the production of:
    • Free radicles
    • DNA hydroxylated bases
  • These cytotoxic enzymes especially predispose oral squamous cell carcinoma.

Alcohol

Carcinogen-metabolizing enzymes are implicated in some patients. Alcohol dehydrogenase oxidizes ethanol to acetaldehyde, which is cytotoxic and results in the production of free radicals and DNA hydroxylated bases; alcohol dehydrogenase type 3 genotypes appear predisposed to OSCC. Cytochrome P450 can activate many environmental procarcinogens. Ethanol is also metabolized to some extent by cytochrome P450 IIEI (CYP2E1) to acetaldehyde. Mutations in some TSGs may be related to cytochrome P450 genotypes and predispose to OSCC. Glutathione S transferase (GST) genotypes may have impaired activity; for example, the null genotype of GSTM1 has a decreased capacity to detoxify tobacco carcinogens. Some GSTM1 and GSTP1 polymorphic genotypes and GSTM1 and GSTT1 null genotypes have been shown to predispose to OSCC. N-acetyltransferases NAT1 and NAT2 acetylate procarcinogens. N-acetyl transferase NAT1*10 genotypes may be a genetic determinant of OSCC, at least in some populations.

Tobacco is a potent risk factor for oral cancer. An interaction occurs between redox-active metals in saliva and the low reactive free radicals in cigarette smoke. The result may be that saliva loses its antioxidant capacity and instead becomes a potent pro-oxidant milieu. null 5

DNA repair genes are clearly involved in the pathogenesis of some rare cancers, such as those that occur in association with xeroderma pigmentosum, but, more recently, evidence of defective DNA repair has also been found to underlie some OSCCs.

An immune deficiency state may predispose one to a higher risk of developing OSCC, especially lip cancer.

Gross Pathological Findings

Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission. © PEIR, University of Alabama at Birmingham, Department of Pathology

{{#ev:youtube|inSkXkNK_dE}}

References

Template:Metabolic pathology

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