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By the end of this seminar you should be able to:

o Define glycogen.

o Describe glycogen storage diseases and their

types.

o Mention causes of these diseases.

o Describe Inheritance of these diseases.

o Identify signs and symptoms of these diseases.

o Describe their diagnosis.o Mention ways of treatment.

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Notice:

There is no adequate information about some of

these diseases and their related enzymes.

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Major storage carbohydrate in animals, mainly

occurs in liver and muscles.

Glycogen

Glycogenesis : after meals

Glycogenolysis : Between meals

Sleep

Sudden exercise

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The pic. shows

Glycogen granule found in the cytosol in the cell

Excess glucose

Storage

Glycogen

Vertebrates

Microorganisms

Starch

Plants

Glycogena(14) glycosidic bond

a(16) glycosidic bond

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This is the process that make a big polymer of

glucose called glycogen

1.Glycogen synthase:

Add UDP-glucose to the glycogen molecule.

Form a(14) glycosidic bond.

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2.Branching enzyme:

It breaks a(14) glycosidic bond.

Then it transfers branch of residues to some

where else.

It makes a(16) glycosidic bond.

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Glycogen Synthase

a(16) glycosidic bond

2

Branching

enzyme

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The enzymes envolved one :

Glycogen Glucose -1 phosphate

1. Glycogen phosphorylase.

2. Glycogen depranching enzyme + glucan

transferase.

3. Phosphoglucomutase.Copy Right Resaved

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Glucan

Transferase

Debranching enzyme

Phosphorylase

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Blo

od

Glycose at the branch

point that debranched

by debranching enzyme

will go directly to the

blood

Glycose 1-P from a(14)

glycosidic bond debranched

by Phosphorylase will

converted to glucose by

Glucose 6-pase (Liver) Or

Phosphoglucomutase

(muscles)

then will go to the blood

2

10

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“Glycogen storage diseases” is a term to

describe a group of inherited disorders

characterized by deposition of an abnormal

type or quantity of glycogen in tissues, or

failure to mobilized glycogen.


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(glycogen synthetase deficiency)

Causes:- Caused by the bodys inability to form a complex

sugar called glycogen due to Mutation in the GYS1

gen and GYS 2 gen

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Inherited in an autosommal recessive pattern.

Inheritance :-

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Signs & symptoms:-

Muscle pain & weakness.

Arrhythmia.

Hypoglycemia.

Ketosis.


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Diagnosis:- liver biopsy.

Urine sample (increased glucose and

ketones in urine).

Genetic DNA test.

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Treatment:-

Prevent low blood sugar.

High protein diet.

Uncooked cornstarch.Copy Right Resaved

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(Von Gierke disease)

Inheritance :-

Autosomal recessive.

Glucose-6-phosphatase deficiency.

Causes:-

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Signs & symptoms:-

Constant hunger and need to eat often.

Frequent infection.

Gout .

Kidney failure.

Liver tumors.

Osteoporosis.

Enlarged liver and kidney.

Low blood glucose.

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Signs & symptoms (cont.) :-

Uric acid: high.

Seizures, lethargy, confusion due to hypoglycemia.

Short height.

Ulcers of the mouth.

Treatment:-

Genetherapy.

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(Pompe Disease)

Cause:-The disease is caused by a mutation in a gene (acid

alpha-glucosidase(maltase) on long arm

of chromosome 17.

Inheritance :-

autosomal recessive metabolic disorder.

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Signs & symptoms:-Infantile onset :

• Cardimypathy.

• Respiratory distress.

• Muscle weakness.

• Cardiomeglay.

• Hypotonia.

• Feeding difficulty.

• Failure to thrive.

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Signs & symptoms (cont.):-

Late onset :

Impaired cough.

Recurrent chest infections.

Hypotonia.

Progressive weakness.

Delayed motor milestones.

Difficulty swallowing or chewing.

Reduce vital capacity.

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Blood samples to determinate the activity of

the enzyme acid alpha glucosidase.

Genetic testing for mutation finding and gene

sequencing.

Diagnosis:-

Treatment:-

enzyme replacement therapy (ERT).

(ERT is given to patients as an intravenous (IV) infusion)

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(Cori disease)

glycogen debranching enzyme deficiency.

Causes:-

Inheritance :-

Mutations in the AGL gene.

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(Cori disease)

Signs & symptoms:-

Hepatomegaly.

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Hepatomegaly17/11/2014

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Signs & symptoms:-

Hypoglycemia.

Cirrhosis.

Hepatomegaly.

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Signs & symptoms:-

Hypoglycemia.

Cirrhosis.

Hyperlipidemia.

Myopathy.

Hypotonia.

Cardiomyopathy.

Hepatomegaly.

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Treatment:-

Treatment may involve a high-protein diet,

in order to facilitate gluconeogenesis

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Causes:- It is result of absence of the glycogen

branching enzyme (amylo 1,4-

1,6transglucosidase) which is critical in

the production of glycogen.

GSD IV is inherited in an autosomal

recessive manner.

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(Andersen’s disease)

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Signs & symptoms:-

In adult the activity of the

enzyme is higher and symptoms

do not appear until later in life.

Cirrhosis .


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Diagnosis:-

Liver and muscles biopsy.

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Treatment:-

Liver transplantation.

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(McArdle Disease)

Glycogen Storage Disease Type V (GSD-V), is

metabolic disorder, more specifically a glycogen

storage disease caused by myophosphorylase.

Cause:-

Myophosphorylase Deficiency (Muscle

Phosphorylase Deficiency)


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Inheritance :-

Mutation in the PYGM gene cause GSD V.

Signs & symptoms:-

exercise intolerance with muscle pain.

early fatigue.

painful cramps.

myoglobin in the urine.


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Diagnosis:-

Muscles biopsy.

Genetic sequencing of the PYGM gene.

Treatment:-

Vitamin B6.

Exercise program.

Sucrose treatment.


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(Hers disease)

Caused by deficiency of hepatic glycogen

phosphorylase.

Causes:-

Inheritance :-

The GSD type VI is inherited in an

autosomal recessive.

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Mild fasting.

Hypoglycemia.

Cirrhosis.

Signs & symptoms:-

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Diagnosis:-

The diagnosis of this disease can be made

by:

Genetic testing from DNA extracted from

blood or saliva.

Liver biopsies to measure phosphorylase

activity, which is reduced in this disease.

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Treatment:-

Uncooked cornstarch & protein diet.

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(Tarui’s)

Glycogen Storage Disease Type VII (GSD-VII), is

metabolic disorder with autosomal recessive

inheritance , caused by Phosphofructokinase

deficiency.


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Signs & symptoms:-

Muscle cramps and weakness.

Myoglobinuria (with hemolytic anemia causing

dark urine a few hours later).

Phosphofructokinase deficiency also present in a

rare infantile form.


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Diagnosis:-

Diagnosis can be made through a muscle

biopsy.

Treatment:-


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(Hepatic phosphorylase kinase deficiency)

Causes:-

By liver phosphorylase kinase deficiency.

Inheritance :-

X-Linked recessive hepatic glycogen disease.

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Signs & symptoms:-

Hypoglycemia.

Hepatomegaly (due to Increase liver glycogen).

Decrease leukocyte phosphorylase.

Growth restriction.

Lactic acidosis.

Affected tissue :

Liver & There is rare cardiac form.

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Diagnosis:-

Blood test.

Urine sample.

Treatment:-

Frequent feeding to avoid hypoglycemia.

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Causes:-Due to liver and muscle (phosphorylase kinase)

deficiency.

Phosphorylase kinase (PhK) is an enzyme which

plays a key role in the regulation of

glycogenolysis as it is required for glycogen

phosphorylase activation.

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Inheritance :-

due to mutations in the PHKA2 or PHKG2 genes

encoding the liver isoforms of the alpha and

gamma subunits of PhK. Transmission is both X-

linked and autosomal recessive as we will see.

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Signs & symptoms:-

Hepatomegaly.

growth retardation.

mild delay in motor development.

Mild muscular hypotonia in childhood.

Exercise intolerance in adolescence or adulthood

Myalgia.

and sometimes myoglobinuria but symptoms are

generally mild.

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Causes:- Defect in the cyclic adenosine monophosphate-

dependent kinase (AMP ) enzyme.

Inheritance :-

X-linked recessive .

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Signs & symptoms:- Hypoglycemia.

Hepatomegaly .

Growth retardation.

muscle cramp.

Anemia.

Increase level of uric acid.

Muscle weakness.

Kidney diseases .

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Diagnosis:-

Blood test.

Urine sample.

Imaging.

Biopsy.

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Treatment:-

The aim of treatment is to maintain normal

blood glucose level.

Allopurinal may be prescribe.

High protein diet.

Limiting strenous exercise.

Gene therapy.

Pepole who not respond to nutritional

supplement may need liver transplantation.

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(Fanconi–Bickel syndrome)

Causes:-

Lactate dehydrogenase deficiency.

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Signs & symptoms:-

Fatigue.

Muscle pain.

Cramps during exercise (exercise intolerance).

Breakdown of muscle tissue (rhabdomyolysis)

in some people.

Brown urine (myoglobinuria).

(may lead to damage the kidneys then renal

failure)

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Affected individuals are usually discovered only

when routine blood tests reveal reduced lactate

dehydrogenase activity.

Diagnosis:-

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By the end of this lecture you should know about:

What is glycogen.

What is glycogen storage diseases and their

types.

Causes of these diseases.

Inheritance of these diseases.

Signs and symptoms of these diseases.

How to these diseases can be diagnosed.

Methods of treatment of these diseases.


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http://en.wikipedia.org/

http://www.agsdus.org/http://www.ncbi.nlm.nih.gov

http://www.patient.co.uk/

Robert K. Murray,Harper’s Illustrated Biochemistry,

29TH Ed.Mc Graw Hill Medical;2012.

Richard A. Harvey,Lippincott's Biochemistry,5TH Ed.

Lippincott Williams & Wilkins;2011.

References :

Websites :

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http://en.wikipedia.org/

http://www.agsdus.org/



The

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Presented BY :

Ahmed Adil Eljack

Israa Mohammed Ahmed

Israa Saeed Elebaid

Ahmed Azhari Abass

Israa Hassan Mohammed

Ahmed Abdalaziz Mohammed

Alaa Abdalaati Abdalla

Rayan Abdalrhman Salih

Ahmed Abdalla Tawer

Hosting :

Esraa Ibrahium Seluman

Alaa Hamza Mohammed

Esraa Isam Aldien Abdalaziz

Eslam Aldardiry Alsaid

Alaa Ibrahium Abadalla

Powerpoint was PrepairedBY:

Ahmed Salah Mohammed

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my 2nd seminar gsds by-argawi

Education

bloodcopy right resavedargawi

glycogen molecule

quantity of glycogen

form a14 glycosidic

a14 glycosidic bond

glucose ishigh

glucose islow

big polymer of glucose