Download GLYCOGEN STORAGE DISEASES LEARNING OBJECTIVES By the

GLYCOGEN STORAGE DISEASES
LEARNING OBJECTIVES
By the end of the lecture the student should be able to :
List different glycogen storage diseases
Describe the biochemical changes involved in glycogen storage
diseases
Gives clinical features, prognosis and treatment of various glycogen
storage diseases
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Glycogen storage diseases (GSDs) these are the group of inherited
disorders associated with glycogen metabolism, familial in incidence
and characterized by deposition of normal or abnormal type and quality
of glycogen in the tissues.
There are several diseases but six are more important diseases.
TYPE 1: Von Gierke’s disease
Enzyme deficient Glucose -6 phosphatase
TYPE 1: VON GIERKE’S DISEASE
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Is the most common of the glycogen storage diseases.
This genetic disease results from deficiency of the enzyme
glucose-6-phosphatase.
This deficiency impairs the ability of the liver to produce free glucose
from glycogen and from gluconeogenesis.
Since these are the two principal metabolic mechanisms by which the
liver supplies glucose to the rest of the body during periods of fasting, it
causes severe hypoglycemia.
Reduced glycogen breakdown results in increased glycogen storage in
liver and kidneys, causing enlargement of both.
Both organs function normally in childhood but are susceptible to a
variety of problems in the adult years.
Other metabolic derangements include lactic acidosis and
hyperlipidemia.
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Frequent or continuous feedings of cornstarch or other carbohydrates
are the principal treatment.
Other therapeutic measures may be needed for associated problems.
Type of glycogen : normal but metabolically not available.
GENETIC PREVALENCE
It is inherited an autosomal recessive disease.
Heterozygote carriers (parents) are asymptomatic. As for other
autosomal recessive diseases, the recurrence risk for each subsequent
child of the same parents is 25%. Prenatal diagnosis has been made by
fetal liver biopsy at 18–22 weeks of gestation, but no fetal treatment has
been proposed.
Prenatal diagnosis is possible with fetal DNA obtained by chorionic villus
sampling when a fetus is known to be at risk.
incidence is approximately 1 in 50,000 to 100,000 births.
TYPE II: POMPE’S DISEASE
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Glycogen storage disease type II (also called Pompe disease or acid
maltase deficiency) is an autosomal recessive metabolic disorder
which damages muscle and nerve cells throughout the body.
It is caused by an accumulation of glycogen in the lysosome due to
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deficiency of the lysosomal acid alpha-glucosidase enzyme.
It is the only glycogen storage disease with a defect in lysosomal
metabolism, and the first glycogen storage disease to be identified, in
1932 by the Dutch pathologist J.C.Pompe.
The build-up of glycogen causes progressive muscle weakness
(myopathy) throughout the body and affects various body tissues,
particularly in the heart, skeletal muscles, liver and nervous system.
SIGNS AND SYMPTOMS
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Infantile
The infantile form usually comes to medical attention within the first few
months of life.
The usual presenting features are cardiomegaly (92%), hypotonia
(88%), cardiomyopathy (88%), respiratory distress (78%), muscle
weakness (63%), feeding difficulties (57%) and failure to thrive (53%).
The main clinical findings include floppy baby appearance, delayed
motor milestones and feeding difficulties.
Moderate hepatomegaly may be present.
Facial features include macroglossia, open mouth, wide open eyes,
nasal flaring (due to respiratory distress), and poor facial muscle tone.
Cardiopulmonary involvement is manifest by increased respiratory
rate, use of accessory muscles for respiration, recurrent chest
infections, decreased air entry in the left lower zone (due to
cardiomegaly), arrhythmias and evidence of heart failure.
Median age at death in untreated cases is 8.7 months and is usually due
to cardiorespiratory failure.
Late onset form
This form differs from the infantile principally in the relative lack of
cardiac involvement.
The onset is more insidious and has a slower progression.
Cardiac involvement may occur but is milder than in the infantile form.
Skeletal involvement is more prominent with a predilection for the lower
limbs.
Late onset features include impaired cough, recurrent chest infections,
hypotonia, progressive muscle weakness, delayed motor milestones,
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difficulty swallowing or chewing and reduced vital capacity.
Prognosis depends on the age of onset on symptoms with a better
prognosis being associated with later onset disease.
TREATMENT
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Cardiac and respiratory complications are treated symptomatically.
Physical and occupational therapy may be beneficial for some patients.
Alterations in diet may provide temporary improvement but will not alter
the course of the disease.
Genetic counseling can provide families with information regarding risk
in future pregnancies.
PROGNOSIS
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The prognosis for individuals with Pompe disease varies according to
the onset and severity of symptoms.
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Without treatment the disease is particularly lethal in infants and young
children.
Pompe’s disease
TYPE III: Limit dextrinosis (Forbe’s disease)
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Glycogen storage disease type III is an autosomal recessive
metabolic disorder and inborn error of metabolism characterized by a
deficiency in glycogen debranching enzymes.
It is also known as Cori's disease in honor of the 1947 Nobel laureates
Carl Cori and Gerty Cori. Other names include Forbes disease in honor
of clinician Gilbert Burnett Forbes (1915-2003), an American Physician
who further described the features of the disorder, or limit dextrinosis.
Glycogen is a molecule the body uses to store carbohydrate energy.
Symptoms of GSD-III are caused by a deficiency of the enzyme
amylo-1,6 glucosidase, or debrancher enzyme. This causes excess
amounts of an abnormal glycogen to be deposited in the liver, muscles
and, in some cases, the heart.
GSD III is inherited in an autosomal recessive pattern, and occurs in
about 1 of every 100,000 live births.
The disease typically presents during infancy with hypoglycemia and
failure to thrive. Clinical examination usually reveals hepatomegaly.
Muscular disease, including hypotonia and cardiomyopathy, usually
occurs later.
The liver pathology typically regresses as patients enter adolescence,
and few patients develop cirrhosis during adulthood.
TYPE IV:
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AMYLOPECTINOSIS (ANDERSON’S DISEASE)
Enzyme deficient : Branching enzyme
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Inheritance : not definitely known.
Organ involved : mainly liver other are muscle and kidney
Type of glycogen : abnormal few branch point and very long inner and
outer chain.
Clinical presentation :
hepatomegaly, splenomegaly, ascites,
moderate hypoglycemia, cirrhosis of liver and hepatic failure
Prognosis: usually fatal longest survival is 4 years.
TYPE V: MCARDLE’S DISEASE
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Enzyme deficient : Muscle phosphorylase
Inheritance : Autosomal recessive
Organ involved : skeletal muscle
Type of glycogen : normal
Clinical presentation : muscle cramps on exercise, pain, weakness and
stiffness of muscle, no lactate is formed as muscle recovers on rest.
TYPE VI: HER’S DISEASE
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Enzyme deficient : liver phosphorylase
Organ involved:
liver and leukocytes
Type of glycogen : normal
Clinical presentation : hepatomegaly, mild to moderate hypoglycemia
and mild acidosis
The end