glycogenstoragediseasegsd-110505030652-phpapp01.ppt

7/27/2019 glycogenstoragediseasegsd-110505030652-phpapp01.ppt

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Glycogen

storage disease

(gsd) Type IV



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



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.



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





Epidiomology

• The overall GSD incidence is estimated at 1 case per

20,000-43,000 live births.



Types

• There are eleven (11) distinct diseases that are commonly

considered to be glycogen storage diseases



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,



Continued…

• Treatment: Liver transplant.

• Prognosis: Mostly death by age 4 due tocirrhosis and portal hypertension.



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



• 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.



Treatment

• No specific treatment exists.

• Avoid strenuous (anaerobic or sustained) exercise,

including lifting or pushing.

• A carbohydrate rich diet did benefit patients.



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.



Continued…

• Treatment: Cardiac transplantation for rare cardiac form.

May need frequent feeding to avoid hypoglycaemia.

• Prognosis: Usually normal life span.



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



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.



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.



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.



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



• Creatinine clearance

• Creatine kinase

• Full blood count



Urine tests:

• Myoglobinuria after exercise found in 50% of people with

McArdle's disease.



Imaging

• Abdominal ultrasound scan: hepatomegaly

• Echocardiography: to look for cardiac involvement in

certain types of GSD



Biopsy

• Of liver.

• Muscle or other tissues gives definitive diagnosis.



Pre-natal diagnosis

• Genetic counseling.

• Referral to geneticist for possible prenatal investigation

(amniotic fluid analysis) and diagnosis.



Differential Diagnosis

• In GSD affecting muscle, exclude the muscular

dystrophies (including Duchenne's) and secondary

disorders of muscle including polymyositis.



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glycogenstoragediseasegsd-110505030652-phpapp01.ppt