My 2nd seminar GSDs by-argawi

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17/11/2014
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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
Notice:
types.
There is no adequate information about some of
these diseases and their related enzymes.
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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 Major storage carbohydrate in animals, mainly
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occurs in liver and muscles.
Glycogen
 Glycogenesis :
 after meals
 Glycogenolysis :
 Between meals
 Sleep
 Sudden exercise
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a(16) glycosidic bond
Glycogen
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Excess glucose
Storage
Glycogen
Vertebrates
Microorganisms
The pic. shows
Starch
Plants
Glycogen granule found in the cytosol in the cell
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 This is the process that make a big polymer of
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glucose called glycogen
1.Glycogen synthase:
 Add UDP-glucose to the glycogen molecule.
 Form a(14) glycosidic bond.
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2.Branching enzyme:
 It breaks a(14) glycosidic bond.
 Then it transfers branch of residues to some
where else.
 It makes a(16) glycosidic bond.
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Glycogen Synthase
2
Branching
enzyme
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Glycogen Glucose -1 phosphate
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 The enzymes envolved one :
1. Glycogen phosphorylase.
2. Glycogen depranching enzyme + glucan
transferase.
3. Phosphoglucomutase.
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Glucan
Transferase
Debranching enzyme
Phosphorylase
Blood
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Glycose 1-P from a(14)
glycosidic bond debranched
by Glycose Phosphorylase at the branch
will
converted point that to debranched
glucose by
Glucose by debranching 6-pase (Liver) enzyme
Or
Phosphoglucomutase
will go directly to the
(muscles)
blood
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
 Inherited in an autosommal recessive pattern.
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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.
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(Von Gierke disease)
Causes:-
 Glucose-6-phosphatase deficiency.
Inheritance :-
 Autosomal recessive.
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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.
 High Lactic acid.
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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.
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Diagnosis:-
Treatment:-
enzyme replacement therapy (ERT).
(ERT is given to patients as an intravenous (IV) infusion)
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(Cori disease)
Causes:-
glycogen debranching enzyme deficiency.
Inheritance :-
 Mutations in the AGL gene.
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(Cori disease)
Signs & symptoms:-
 Hepatomegaly.
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Hepatomegaly
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Signs & symptoms:-
 Hepatomegaly.
 Hypoglycemia.
 Cirrhosis.
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Signs & symptoms:-
 Hepatomegaly.
 Hypoglycemia.
 Cirrhosis.
 Hyperlipidemia.
 Myopathy.
 Hypotonia.
 Cardiomyopathy.
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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:-
 Cirrhosis .
 In adult the activity of the
enzyme is higher and symptoms
do not appear until later in life.
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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)
Causes:-
 Caused by deficiency of hepatic glycogen
phosphorylase.
Inheritance :-
 The GSD type VI is inherited in an
autosomal recessive.
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Signs & symptoms:-
Mild fasting.
Hypoglycemia.
Cirrhosis.
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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.
(During adulthood, symptoms usually disappear).
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Causes:-
 Defect in the cyclic adenosine monophosphate-dependent
kinase (AMP ) enzyme.
Inheritance :-
 X-linked recessive .
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17/11/2014
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.
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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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References :
 Robert K. Murray,Harper’s Illustrated Biochemistry,
 Richard A. Harvey,Lippincott's Biochemistry,5TH Ed.
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29TH Ed.Mc Graw Hill Medical;2012.
Lippincott Williams & Wilkins;2011.
Websites :
http://en.wikipedia.org/
http://www.agsdus.org/
http://www.ncbi.nlm.nih.gov
http://www.patient.co.uk/
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The
End
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Powerpoint was Prepaired
Presented BY :
Hosting :
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
Esraa Ibrahium Seluman
Alaa Ahmed Hamza Salah Mohammed
Mohammed
Esraa Isam Aldien Abdalaziz
Eslam Aldardiry Alsaid
Alaa Ibrahium Abadalla
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My 2nd seminar GSDs by-argawi

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