Pompe disease is a rare (estimated at 1 in every 40,000 births), inherited and often fatal disorder that disables the heart and skeletal muscles. It is caused by mutations in a gene that makes an enzyme called acid alpha-glucosidase (GAA).

1. POMPE’S DISEASE

2. INTRODUCTION
• Pompe’s disease is an autosomal
recessive inherited disorder due
to autosomal recessive mutations
in the GAA gene that cause
build-up of a complex sugar
called glycogen in the body's
cells. The accumulation of
glycogen in certain organs and
tissues, especially muscles,
impairs their ability to function
normally.

3. It was first described in 1932 by a Dutch
pathologist, Johannes Pompe’s, when he
noted ubiquitous (present everywhere)
deposition of glycogen in vacuoles in
the heart and other tissues of a 7-month-
old girl who had died from hypertrophic
cardiomyopathy. In 1963, HG Cori
classified it as glycogen storage disease
type II

4.  Pompe’s disease affects about 1 in 40,000 people,
although the precise number is not known as the
disease can be difficult to diagnose and there may
be larger numbers of unrecognized patients. Males
and females are affected in equal numbers
 Researchers have described three types of Pompe’s
disease, which differ in severity and the age at which
they appear. These types are known as classic infantile-
onset, non-classic infantile-onset, and late-onset.

5. OTHER NAMES OF POMPE DISEASE
 glycogen storage disease type II
 acid maltase deficiency (AMD
 acid alpha-glucosidase (GAA) deficiency

6. CAUSE
It has an autosomal recessive inheritance
pattern. This means the defective gene is
located on an autosome,
and two copies of the gene—one from each
parent—are required to be born with the
disorder.
As with all cases of autosomal recessive
inheritance, children have a 1 in 4 chance of
inheriting the disorder when both parents
carry the defective gene, and although both
parents carry one copy of the defective gene,
they are usually not affected by the disorder.

7. NORMAL PROCESS OF GLYCOGENOLYSIS (it is the
breakdown of the molecule glycogen into glucose) BY LYSOMES

8. PATHOPHYSIOLOGY OF POMPE’S
DISEASE
In pompe’s disease there is a mutation in GAA gene(The GAA
gene is located on chromosome 17 and provides instructions for producing an
enzyme called acid alpha-glucosidase)
This mutation prevents the production of enough functional Acid alpha-
glucosidase

10. And as a result of this lysosomes can’t
breakdown glycogen to glucose and leads to
a build-up of glycogen in the cytoplasm and
within lysosome
And that leads to cellular damage and
destruction

11. NORMALLY IN POMPE’S DISEASE
Glycogen is found in largest amount
in the cytoplasm of :-
Glycogen mostly accumulates in the
lysosomes of :-

12. THE THREE TYPES OF POMPE’S
DISEASE
Classic infantile-onset - begins within a few months of birth. If untreated, this form
of Pompe disease leads to death from heart failure in the first year of life. Infants with
this disorder typically experience
 progressive muscle weakness (floppy infants),
 diminished muscle tone (hypotonia),
 respiratory insufficiency, and have breathing problems
 a type of heart disease known as hypertrophic cardiomyopathy, a condition
characterized by abnormal thickening of the walls of the heart(mainly the left
chamber and the wall between the left and right chamber) resulting in diminished,

14.  an enlarged liver (hepatomegaly),
 Many infants have a large, protruding tongue ,
 The legs often rest in a frog position and feel firm on palpation
(pseudo-hypertrophy).
pseudo-hypertrophy

15. CONT…….
Affected infants may also fail to gain weight and grow at the
expected rate (failure to thrive).
Feeding and swallowing problems which are often combined with
respiratory tract infections, are common.
Delayed or not achieved Major developmental milestones
such as rolling over, sitting up, and standing.
Mental development is usually normal.
Virtually all infants experience hearing loss

16. Non-classic infantile-onset
Non-classic infantile-onset- usually appears by age
1. It is characterized by
 delayed motor skills (such as rolling over and
sitting) and progressive muscle weakness.
 The heart may be abnormally large (cardiomegaly),
but affected individuals usually do not experience
heart failure.
 The muscle weakness in this disorder leads to
serious breathing problems, and
• most children with non-classic infantile-
onset Pompe disease live only into early childhood

17. late-onset
late-onset type of Pompe disease may not become apparent until later in childhood,
adolescence, or adulthood. Late-onset Pompe disease is usually milder than the
infantile-onset forms of this disorder and is less likely to involve the heart. Most
individuals with late-onset Pompe disease experience
 progressive muscle weakness, mainly the proximal muscles (limb girdle, upper
arms and upper legs), The lower limbs are more affected than the upper limbs. and
 varying degrees of respiratory weakness due to dysfunction of the diaphragm and
intercostal muscles (muscle between ribs).
 The muscles adjacent to the spinal column (para-spinal muscles) and neck are
usually also involved. Weakness of the para-spinal muscles around puberty can
cause abnormal curvature of the spine (scoliosis).

18. para-spinal
muscles

19. Other symptoms can include chewing and swallowing
difficulties
drooping of the upper eyelids (ptosis).
Additionally, blood vessel
abnormalities due to smooth muscle weakness and
problems of the urinary and digestive systems have been
reported.
As the disorder progresses, breathing problems can lead to
respiratory failure.

21. DIAGNOSIS
A diagnosis of Pompe disease is based upon a thorough clinical evaluation, a
detailed patient and family history.
Prenatal diagnosis is possible when a pregnancy is believed to be at risk for
Pompe disease.
In individuals suspected of having Pompe disease, blood can be drawn and
the function/activity of the GAA enzyme can be measured in white blood
cells (leukocytes) and on a dried blood spot. The advantage of the bloodspot
test is that it allows convenient shipment of samples Additionally, dried blood
spot testing allows for mass screening. The reason for stability of DNA, RNA
or protein in dried blood spot test could be attributed to the fact that the
biological material binds to the matrix of the filter paper

22. bloodspot
test

23. Pompe disease diagnosis must be confirmed through molecular genetic testing
(DNA analysis) or by another enzyme assay, preferably using cultured skin
fibroblasts obtained by a skin biopsy. The GAA enzyme activity test by skin
biopsy is superior over others as it is the most sensitive test and discriminates
best between classic-infantile, childhood and adult Pompe disease.

24. A variety of additional tests may be performed to detect or assess
symptoms potentially associated with Pompe disease such as
1.Sleep studies or breathing tests to measure lung capacity,
2.Electromyography, test to measure muscle function.
3.Muscle MRI’s are also used to measure the degree of damage that
has occurred to the muscles.
4.Chest x-rays, allows physicians to assess the size of the heart,
5.Electrocardiogram, it measures the electrical activity of the heart
and can detect abnormal heart rhythms
6.Echocardiogram it uses reflected sound waves to create a picture
of the heart and can reveal abnormal thickening of the heart muscle
tissue.

25. If the specific GAA gene mutations in both parents are known, prenatal
diagnosis is possible through chorionic villi sampling (CVS) or
amniocentesis.

26. Pre-implantation genetic diagnosis (testing an embryo to determine whether
it has the same genetic abnormalities as the parents) may also be an option.
PGD can be performed on embryos created through in vitro fertilization (is an
assisted reproductive technology (ART) commonly referred to as IVF).

27. TREATMENT
The treatment of Pompe disease is disease-specific, symptomatic, and
supportive. Treatment requires the coordinated efforts of a team of
specialists with expertise in treating neuromuscular disorders.
1. Paediatricians ,
2. neurologists,
3. orthopedists,
4. cardiologists,
5. dieticians, and
6. social workers
7. other healthcare professionals may need to systematically and
comprehensively plan an affect child’s treatment.
8. Genetic counselling is of utmost importance for affected individuals and their
families.

28. ENZYME REPLACEMENT THERAPY
Enzyme replacement therapy is an approved treatment for all patients with Pompe disease. It involves the
intravenous administration of recombinant human acid α-glucosidase. This treatment, manufactured by
Genzyme, a Sanofi Corporation, is Lumizyme (marketed as Myozyme outside the United States), and was
first approved by the U.S. Food and Drug Administration (FDA) in 2006. It has been approved for all
patients with Pompe disease, but this requires lifelong administration

29. DRUG STUDY
• INDICATIONS AND USAGE
LUMIZYME (alglucosidase alfa) is a lysosomal glycogen-specific enzyme indicated
for patients 8 years and older with late (non-infantile) onset Pompe disease (GAA
deficiency) who do not have evidence of cardiac hypertrophy. The safety and efficacy
of LUMIZYME have not been evaluated in controlled clinical trials in infantile-onset
patients, or in late (non-infantile) onset patients less than 8 years of age
• DOSAGE AND ADMINISTRATION
The recommended dosage of LUMIZYME is 20 mg/kg body weight administered every
2 weeks as an intravenous infusion.
• DOSAGE FORMS AND STRENGTHS
• Dosage form: Lyophilized powder for solution for intravenous infusion
• Dosage strength: 5 mg/mL
• CONTRAINDICATIONS: - None.

30. WARNINGS AND PRECAUTIONS
• Life-threatening anaphylactic reactions have been observed in some patients during
LUMIZYME infusions. Ensure that appropriate medical support measures, including
cardiopulmonary resuscitation equipment are readily available when LUMIZYME is
administered
• If severe allergic or anaphylactic reactions occur, consider immediate discontinuation of
the administration of LUMIZYME and initiate appropriate medical treatment.
• Severe cutaneous and systemic immune mediated reactions can occur with alglucosidase
alfa. Therefore, monitor patients for the development of systemic immune complex-
mediated reactions involving skin and other organs while receiving LUMIZYME
ADVERSE REACTIONS
• The most frequently reported adverse reactions (≥5%) in clinical studies were infusion
reactions and included:
anaphylaxis(severe allergic reaction), urticaria(pale red bumps), diarrhoea, vomiting,
dyspnea, pruritus, rash/erythema, pharyngolaryngeal pain, neck pain, hypoacusis,
flushing/feeling hot, pain in extremity, fall and chest discomfort

31. GENE THERAPY:
It is in early stages of research but could offer a way to restore the bodies
ability to function properly with only a single administration In this a working
version of faulty gene can be delivered into the cells to instruct them to
produce the essential protein or enzyme, this could eliminate the need for
enzyme therapy
The working GAA gene need to be delivered into the cells using a vector
which are often extracted by viruses by removing all the viral genes from
that vector and the vector is modified to only deliver the therapeutic
gene

32. vector
Therapeutic
gene

33. Vectors can be delivered by:-
EX- VIVO IN-VIVO APPROACH
The treatment occurs outside of your body
Some of the stem cells removed from the
body because they can be developed into
different types of cells depending upon what
the body needs
The treatment occurs inside of your body
A vector with working GAA injected into the
vein
In the circulation the vector delivers the
functional gene to the key organs like heart,
liver, brain and the muscles

34. A vector with GAA gene is delivered to these cells
and then the modified cells are infused in the
body via an infusion with the hope to slow or
stop the pompe’s disease
Each part of the body can then
make the GAA enzyme and can
fully restore enzyme function as
needed

35. SUPPORTIVE THERAPIES
Additional treatment of Pompe disease is symptomatic and supportive. Respiratory
support may be required, as most patients have some degree of respiratory compromise
and/or respiratory failure. Some patients may need respiratory assistance through
mechanical ventilation (i.e. bipap or volume ventilators) during the night and/or periods of
the day. In addition, it may be necessary for additional support during respiratory tract
infections. Mechanical ventilation support can be through noninvasive or invasive
techniques. The decision about the duration of respiratory support is best made by the family
in careful consultation with the patient’s physicians and other members of the healthcare
team based upon the specifics of the patient.
• Physical therapy may be helpful to strengthen respiratory muscles.
• Physiotherapy is recommended to improve strength and physical ability.
• Occupational therapy, including the use of canes or walkers, may be necessary.
Eventually, some individuals may require the use of a wheelchair.

36. CONT…..
• Speech therapy can be beneficial to improve articulation and speech for some
patients.
• Orthopaedic devices including braces may be recommended for some patients.
• Surgery may be required for certain orthopaedic symptoms such as contractures
or spinal deformity.
• Since Pompe disease can weaken muscles used for chewing and swallowing,
adequate measures may be required to ensure proper nutrition and weight gain.
Some patients may need specialized, high-calorie diets and may need to learn
techniques to change the size and texture of food to lower the risk of aspiration.
Some infants may require the insertion of a feeding tube. In some children, a
feeding tube may need to be inserted directly into the stomach through a small
surgical opening in the abdominal wall. Some individuals with late onset Pompe
disease may require a soft diet, but few require feeding tubes.

37. PROGNOSIS
• The prognosis for individuals with Pompe disease varies according to the onset and
severity of symptoms, along with lifestyle factors. Without treatment the infantile form
of the disease is particularly lethal.
• In a study which included the largest cohort of patients with Pompe disease treated with
enzyme replacement therapy (ERT) to date findings showed that Myozyme treatment
clearly prolongs ventilator-free survival and overall survival in patients with infantile-
onset Pompe disease as compared to an untreated historical control population.
• Furthermore, the study demonstrated that initiation of ERT prior to 6 months of age,
which could be facilitated by newborn screening, shows great promise to reduce the
mortality and disability associated with this devastating disorder. many of these babies
have reached the normal motor developmental milestones.

38. NURSING RESPONSBILITY:-
• Altered nutritional status
• Impaired deglutition
• Aspiration risk
• Risk of infection
• Risk of impaired breathing
• Risk for pressure ulcers
• Impaired mobility
• Communication impaired
• Family fear and anxiety