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Glycogen storage
disease (gsd)
Type IV
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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
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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.
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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 affecttissues such as the kidney, heart and bowel.
The classification of glycogen storage disorders is based
on the enzyme deficiency and the affected tissue.
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Epidiomology
The overall GSD incidence is estimated at 1 case per
20,000-43,000 live births.
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Types
There are eleven (11) distinct diseases that are commonly
considered to be glycogen storage diseases
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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,jaundice, hypotonia, waddling gait, lumbar lordosis.
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Continued
Treatment: Liver transplant.
Prognosis: Mostly death by age 4 due tocirrhosis and portal hypertension.
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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
muscle wasting may be present.
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The fatal infantile form presents with hypotonia and
reduced reflexes.
Ischaemic forearm test: traditional test but is painful andnon-ischaemic exercise tests are now preferred.
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Treatment
No specific treatment exists.
Avoid strenuous (anaerobic or sustained) exercise,
including lifting or pushing.
A carbohydrate rich diet did benefit patients.
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Type VI, Hers disease
Affected enzyme: Liver phosphorylase.
Affected tissues: Liver, rare cardiac form.
Clinical features:
Most common variant is X-linked therefore usually
affects only males.
Hepatomegaly, hypoglycaemia, growth retardation,
hyperlipidaemia.
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Continued
Treatment: Cardiac transplantation for rare cardiac form.
May need frequent feeding to avoid hypoglycaemia.
Prognosis: Usually normal life span.
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Type VII, Tarui disease
Cause: Phosphofructokinase (PFK) deficiency
Affected tissue: Muscle
Clinical features:
Exercise intolerance, muscle cramping, exertionalmyopathy, compensated haemolysis and myoglobinuria.
Note : Symptoms can be similar to McArdle's Glycogen
Storage Disease but more severe.
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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.
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Type XI, Fanconi-Bickel
syndrome Affected enzyme: Glucose transporter GLUT2 [solutecarrier family 2 ,facilitated glucose transporter]
Clinical features: Similar features to Von Gierke'sdisease, e.g. hypoglycaemia.
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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.
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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
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Creatinine clearance
Creatine kinase
Full blood count
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Urine tests:
Myoglobinuria after exercise found in 50% of people with
McArdle's disease.
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Imaging
Abdominal ultrasound scan: hepatomegaly
Echocardiography: to look for cardiac involvement in
certain types of GSD
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Biopsy
Of liver.
Muscle or other tissues gives definitive diagnosis.
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Pre-natal diagnosis
Genetic counseling.
Referral to geneticist for possible prenatal investigation
(amniotic fluid analysis) and diagnosis.
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Differential Diagnosis
In GSD affecting muscle, exclude the muscular
dystrophies (including Duchenne's) and secondary
disorders of muscle including polymyositis.
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