glycogenstoragediseasegsd-110505030652-phpapp01.odp

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

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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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