glycogenstoragediseasegsd-110505030652-phpapp01.ppt
-
Upload
anonymous-t5tdwd -
Category
Documents
-
view
221 -
download
0
Transcript of glycogenstoragediseasegsd-110505030652-phpapp01.ppt
![Page 1: glycogenstoragediseasegsd-110505030652-phpapp01.ppt](https://reader031.fdocuments.net/reader031/viewer/2022020718/577cd6ef1a28ab9e789d9a79/html5/thumbnails/1.jpg)
7/27/2019 glycogenstoragediseasegsd-110505030652-phpapp01.ppt
http://slidepdf.com/reader/full/glycogenstoragediseasegsd-110505030652-phpapp01ppt 1/26
Glycogen
storage disease
(gsd) Type IV
![Page 2: glycogenstoragediseasegsd-110505030652-phpapp01.ppt](https://reader031.fdocuments.net/reader031/viewer/2022020718/577cd6ef1a28ab9e789d9a79/html5/thumbnails/2.jpg)
7/27/2019 glycogenstoragediseasegsd-110505030652-phpapp01.ppt
http://slidepdf.com/reader/full/glycogenstoragediseasegsd-110505030652-phpapp01ppt 2/26
Case
• A 10-month-old male infant presented with massive
hepatomegaly. There was no history of jaundice, fever,
weight loss, blood in stool, or acholic stool. He was born
at full term without any complications, and the newborn
screening test results were normal.
• Biopsy of the liver shows the presence of the associated
abnormal glycogen
![Page 3: glycogenstoragediseasegsd-110505030652-phpapp01.ppt](https://reader031.fdocuments.net/reader031/viewer/2022020718/577cd6ef1a28ab9e789d9a79/html5/thumbnails/3.jpg)
7/27/2019 glycogenstoragediseasegsd-110505030652-phpapp01.ppt
http://slidepdf.com/reader/full/glycogenstoragediseasegsd-110505030652-phpapp01ppt 3/26
Introduction
• Glycogen is a branched-chain polymer of glucose and
serves as a dynamic but limited reservoir of glucose,
mainly in skeletal muscle and liver.
• There are a number of different enzymes involved in
glycogen synthesis, utilization and breakdown within the
body.
![Page 4: glycogenstoragediseasegsd-110505030652-phpapp01.ppt](https://reader031.fdocuments.net/reader031/viewer/2022020718/577cd6ef1a28ab9e789d9a79/html5/thumbnails/4.jpg)
7/27/2019 glycogenstoragediseasegsd-110505030652-phpapp01.ppt
http://slidepdf.com/reader/full/glycogenstoragediseasegsd-110505030652-phpapp01ppt 4/26
Continued…
• Glycogen storage disorders (GSD) are a group of
inherited inborn errors of metabolism due to deficiency or
dysfunction of these enzymes.
• confined to just liver and muscle
• But some cause more generalised pathology and affect
tissues such as the kidney, heart and bowel.
• The classification of glycogen storage disorders is based
![Page 5: glycogenstoragediseasegsd-110505030652-phpapp01.ppt](https://reader031.fdocuments.net/reader031/viewer/2022020718/577cd6ef1a28ab9e789d9a79/html5/thumbnails/5.jpg)
7/27/2019 glycogenstoragediseasegsd-110505030652-phpapp01.ppt
http://slidepdf.com/reader/full/glycogenstoragediseasegsd-110505030652-phpapp01ppt 5/26
![Page 6: glycogenstoragediseasegsd-110505030652-phpapp01.ppt](https://reader031.fdocuments.net/reader031/viewer/2022020718/577cd6ef1a28ab9e789d9a79/html5/thumbnails/6.jpg)
7/27/2019 glycogenstoragediseasegsd-110505030652-phpapp01.ppt
http://slidepdf.com/reader/full/glycogenstoragediseasegsd-110505030652-phpapp01ppt 6/26
Epidiomology
• The overall GSD incidence is estimated at 1 case per
20,000-43,000 live births.
![Page 7: glycogenstoragediseasegsd-110505030652-phpapp01.ppt](https://reader031.fdocuments.net/reader031/viewer/2022020718/577cd6ef1a28ab9e789d9a79/html5/thumbnails/7.jpg)
7/27/2019 glycogenstoragediseasegsd-110505030652-phpapp01.ppt
http://slidepdf.com/reader/full/glycogenstoragediseasegsd-110505030652-phpapp01ppt 7/26
Types
• There are eleven (11) distinct diseases that are commonly
considered to be glycogen storage diseases
![Page 8: glycogenstoragediseasegsd-110505030652-phpapp01.ppt](https://reader031.fdocuments.net/reader031/viewer/2022020718/577cd6ef1a28ab9e789d9a79/html5/thumbnails/8.jpg)
7/27/2019 glycogenstoragediseasegsd-110505030652-phpapp01.ppt
http://slidepdf.com/reader/full/glycogenstoragediseasegsd-110505030652-phpapp01ppt 8/26
Type IV, Andersen's disease• Affected enzyme: Absence of the glycogen branching
enzyme amylo-1,4-1,6 transglucosidase, which is critical
in the production of glycogen. This leads to very long
unbranched glucose chains being stored in glycogen. The
long unbranched molecules have a low solubility which
leads to glycogen precipitation in the liver.
• Affected tissues: Heart and liver. Rare variant affects
peripheral nerves.
• Clinical features:
• Hepatomegaly, failure to thrive, cirrhosis, splenomegaly,
![Page 9: glycogenstoragediseasegsd-110505030652-phpapp01.ppt](https://reader031.fdocuments.net/reader031/viewer/2022020718/577cd6ef1a28ab9e789d9a79/html5/thumbnails/9.jpg)
7/27/2019 glycogenstoragediseasegsd-110505030652-phpapp01.ppt
http://slidepdf.com/reader/full/glycogenstoragediseasegsd-110505030652-phpapp01ppt 9/26
Continued…
• Treatment: Liver transplant.
• Prognosis: Mostly death by age 4 due tocirrhosis and portal hypertension.
![Page 10: glycogenstoragediseasegsd-110505030652-phpapp01.ppt](https://reader031.fdocuments.net/reader031/viewer/2022020718/577cd6ef1a28ab9e789d9a79/html5/thumbnails/10.jpg)
7/27/2019 glycogenstoragediseasegsd-110505030652-phpapp01.ppt
http://slidepdf.com/reader/full/glycogenstoragediseasegsd-110505030652-phpapp01ppt 10/26
Type V, McArdle's disease
Cause: Myophosphorylase deficiency
Affected tissue: Muscle
Clinical features
• Clinical findings may be absent on physical examination.
Muscle strength and reflexes may be normal
• In later adult life, persistent proximal weakness and
![Page 11: glycogenstoragediseasegsd-110505030652-phpapp01.ppt](https://reader031.fdocuments.net/reader031/viewer/2022020718/577cd6ef1a28ab9e789d9a79/html5/thumbnails/11.jpg)
7/27/2019 glycogenstoragediseasegsd-110505030652-phpapp01.ppt
http://slidepdf.com/reader/full/glycogenstoragediseasegsd-110505030652-phpapp01ppt 11/26
• The fatal infantile form presents with hypotonia and
reduced reflexes.
• Ischaemic forearm test: traditional test but is painful and
non-ischaemic exercise tests are now preferred.
![Page 12: glycogenstoragediseasegsd-110505030652-phpapp01.ppt](https://reader031.fdocuments.net/reader031/viewer/2022020718/577cd6ef1a28ab9e789d9a79/html5/thumbnails/12.jpg)
7/27/2019 glycogenstoragediseasegsd-110505030652-phpapp01.ppt
http://slidepdf.com/reader/full/glycogenstoragediseasegsd-110505030652-phpapp01ppt 12/26
Treatment
• No specific treatment exists.
• Avoid strenuous (anaerobic or sustained) exercise,
including lifting or pushing.
• A carbohydrate rich diet did benefit patients.
![Page 13: glycogenstoragediseasegsd-110505030652-phpapp01.ppt](https://reader031.fdocuments.net/reader031/viewer/2022020718/577cd6ef1a28ab9e789d9a79/html5/thumbnails/13.jpg)
7/27/2019 glycogenstoragediseasegsd-110505030652-phpapp01.ppt
http://slidepdf.com/reader/full/glycogenstoragediseasegsd-110505030652-phpapp01ppt 13/26
Type VI, Hers disease
• Affected enzyme: Liver phosphorylase.
• Affected tissues: Liver, rare cardiac form.
• Clinical features:
• Most common variant is X-linked therefore usuallyaffects only males.
• Hepatomegaly, hypoglycaemia, growth retardation,
hyperlipidaemia.
![Page 14: glycogenstoragediseasegsd-110505030652-phpapp01.ppt](https://reader031.fdocuments.net/reader031/viewer/2022020718/577cd6ef1a28ab9e789d9a79/html5/thumbnails/14.jpg)
7/27/2019 glycogenstoragediseasegsd-110505030652-phpapp01.ppt
http://slidepdf.com/reader/full/glycogenstoragediseasegsd-110505030652-phpapp01ppt 14/26
Continued…
• Treatment: Cardiac transplantation for rare cardiac form.
May need frequent feeding to avoid hypoglycaemia.
• Prognosis: Usually normal life span.
![Page 15: glycogenstoragediseasegsd-110505030652-phpapp01.ppt](https://reader031.fdocuments.net/reader031/viewer/2022020718/577cd6ef1a28ab9e789d9a79/html5/thumbnails/15.jpg)
7/27/2019 glycogenstoragediseasegsd-110505030652-phpapp01.ppt
http://slidepdf.com/reader/full/glycogenstoragediseasegsd-110505030652-phpapp01ppt 15/26
Type VII, Tarui disease
Cause: Phosphofructokinase (PFK) deficiency
Affected tissue: Muscle
Clinical features:
• Exercise intolerance, muscle cramping, exertional
myopathy, compensated haemolysis and myoglobinuria.
Note : Symptoms can be similar to McArdle's Glycogen
![Page 16: glycogenstoragediseasegsd-110505030652-phpapp01.ppt](https://reader031.fdocuments.net/reader031/viewer/2022020718/577cd6ef1a28ab9e789d9a79/html5/thumbnails/16.jpg)
7/27/2019 glycogenstoragediseasegsd-110505030652-phpapp01.ppt
http://slidepdf.com/reader/full/glycogenstoragediseasegsd-110505030652-phpapp01ppt 16/26
Treatment:
No specific treatment exists.
There is evidence that a high protein diet may
improve muscle function and slow progression of
the disease.
Vigorous exercise should be avoided as it causes
myoglobinuria.
![Page 17: glycogenstoragediseasegsd-110505030652-phpapp01.ppt](https://reader031.fdocuments.net/reader031/viewer/2022020718/577cd6ef1a28ab9e789d9a79/html5/thumbnails/17.jpg)
7/27/2019 glycogenstoragediseasegsd-110505030652-phpapp01.ppt
http://slidepdf.com/reader/full/glycogenstoragediseasegsd-110505030652-phpapp01ppt 17/26
Type XI, Fanconi-Bickel
syndrome• Affected enzyme: Glucose transporter GLUT2 [solute
carrier family 2 ,facilitated glucose transporter]
• Clinical features: Similar features to Von Gierke's
disease, e.g. hypoglycaemia.
![Page 18: glycogenstoragediseasegsd-110505030652-phpapp01.ppt](https://reader031.fdocuments.net/reader031/viewer/2022020718/577cd6ef1a28ab9e789d9a79/html5/thumbnails/18.jpg)
7/27/2019 glycogenstoragediseasegsd-110505030652-phpapp01.ppt
http://slidepdf.com/reader/full/glycogenstoragediseasegsd-110505030652-phpapp01ppt 18/26
Type 0, Lewis disease
• Affected enzyme: Hepatic glycogen synthase.
• Affected tissues: Liver.
• Clinical features
• Seizures can occur.
• Fatigue and muscle cramps after exertion.
• Mild growth retardation in some cases.
![Page 19: glycogenstoragediseasegsd-110505030652-phpapp01.ppt](https://reader031.fdocuments.net/reader031/viewer/2022020718/577cd6ef1a28ab9e789d9a79/html5/thumbnails/19.jpg)
7/27/2019 glycogenstoragediseasegsd-110505030652-phpapp01.ppt
http://slidepdf.com/reader/full/glycogenstoragediseasegsd-110505030652-phpapp01ppt 19/26
Investigation
Blood tests:
• Blood glucose: hypoglycaemia is likely
• Liver function tests: monitoring for hepatic
failure
• Anion gap calculation: if glucose low, this may
indicate lactic acidaemia
![Page 20: glycogenstoragediseasegsd-110505030652-phpapp01.ppt](https://reader031.fdocuments.net/reader031/viewer/2022020718/577cd6ef1a28ab9e789d9a79/html5/thumbnails/20.jpg)
7/27/2019 glycogenstoragediseasegsd-110505030652-phpapp01.ppt
http://slidepdf.com/reader/full/glycogenstoragediseasegsd-110505030652-phpapp01ppt 20/26
• Creatinine clearance
• Creatine kinase
• Full blood count
![Page 21: glycogenstoragediseasegsd-110505030652-phpapp01.ppt](https://reader031.fdocuments.net/reader031/viewer/2022020718/577cd6ef1a28ab9e789d9a79/html5/thumbnails/21.jpg)
7/27/2019 glycogenstoragediseasegsd-110505030652-phpapp01.ppt
http://slidepdf.com/reader/full/glycogenstoragediseasegsd-110505030652-phpapp01ppt 21/26
Urine tests:
• Myoglobinuria after exercise found in 50% of people with
McArdle's disease.
![Page 22: glycogenstoragediseasegsd-110505030652-phpapp01.ppt](https://reader031.fdocuments.net/reader031/viewer/2022020718/577cd6ef1a28ab9e789d9a79/html5/thumbnails/22.jpg)
7/27/2019 glycogenstoragediseasegsd-110505030652-phpapp01.ppt
http://slidepdf.com/reader/full/glycogenstoragediseasegsd-110505030652-phpapp01ppt 22/26
Imaging
• Abdominal ultrasound scan: hepatomegaly
• Echocardiography: to look for cardiac involvement in
certain types of GSD
![Page 23: glycogenstoragediseasegsd-110505030652-phpapp01.ppt](https://reader031.fdocuments.net/reader031/viewer/2022020718/577cd6ef1a28ab9e789d9a79/html5/thumbnails/23.jpg)
7/27/2019 glycogenstoragediseasegsd-110505030652-phpapp01.ppt
http://slidepdf.com/reader/full/glycogenstoragediseasegsd-110505030652-phpapp01ppt 23/26
Biopsy
• Of liver.
• Muscle or other tissues gives definitive diagnosis.
![Page 24: glycogenstoragediseasegsd-110505030652-phpapp01.ppt](https://reader031.fdocuments.net/reader031/viewer/2022020718/577cd6ef1a28ab9e789d9a79/html5/thumbnails/24.jpg)
7/27/2019 glycogenstoragediseasegsd-110505030652-phpapp01.ppt
http://slidepdf.com/reader/full/glycogenstoragediseasegsd-110505030652-phpapp01ppt 24/26
Pre-natal diagnosis
• Genetic counseling.
• Referral to geneticist for possible prenatal investigation
(amniotic fluid analysis) and diagnosis.
![Page 25: glycogenstoragediseasegsd-110505030652-phpapp01.ppt](https://reader031.fdocuments.net/reader031/viewer/2022020718/577cd6ef1a28ab9e789d9a79/html5/thumbnails/25.jpg)
7/27/2019 glycogenstoragediseasegsd-110505030652-phpapp01.ppt
http://slidepdf.com/reader/full/glycogenstoragediseasegsd-110505030652-phpapp01ppt 25/26
Differential Diagnosis
• In GSD affecting muscle, exclude the muscular
dystrophies (including Duchenne's) and secondary
disorders of muscle including polymyositis.
![Page 26: glycogenstoragediseasegsd-110505030652-phpapp01.ppt](https://reader031.fdocuments.net/reader031/viewer/2022020718/577cd6ef1a28ab9e789d9a79/html5/thumbnails/26.jpg)
7/27/2019 glycogenstoragediseasegsd-110505030652-phpapp01.ppt
http://slidepdf.com/reader/full/glycogenstoragediseasegsd-110505030652-phpapp01ppt 26/26