Pompe disease, also known as acid maltase
deficiency (AMD) or glycogen storage disease
II, is a rare, inherited glycogen storage disease
that aects the heart and skeletal muscles.
There are two types of Pompe disease: infantile-
onset and noninfantile-onset (juvenile or adult).
Pompe is classified as a metabolic muscle
disorder, one of a group of diseases that
interferes with processing and storage
of complex sugars (carbohydrates). The
build-up of sugar molecules in muscle
cells causes them to break down.
This rare disease is estimated to occur
in approximately 1 in every 22,000
births based on studies of newborn
screening eorts in the United States.
Mutations in a gene that carries the genetic
instructions to make an enzyme called acid
maltase, or acid alpha-glucosidase (GAA),
are the underlying cause of Pompe disease.
Normally, the body uses the GAA enzyme to
break down glycogen (stored sugar used for
energy). The enzyme performs its function in
intracellular compartments called lysosomes,
which gather several substances, including
glycogen. There GAA converts glycogen into
glucose, which is used to fuel cells. In Pompe
disease, mutations in the GAA gene reduce or
completely eliminate this essential enzyme.
Muscle weakness is a main symptom
in both forms of Pompe disease.
Pompe disease severity and age of
onset are related to how much functional
GAA enzyme is present in cells.
Excessive amounts of lysosomal glycogen
accumulate everywhere in the body, but the
cells of the heart and skeletal muscles are
the most seriously aected. Accumulation
of glycogen in these tissues destroys
healthy muscle and heart tissues.
Researchers have identified at least 550
dierent mutations in the GAA gene that
cause the symptoms of Pompe disease.
Although Pompe is a single disease, it is
classified into two forms. The early-onset
infantile form is the more severe of the
two. It starts before 12 months of age and
involves the heart muscle. The later-onset
juvenile or adult form may start at any
age after 12 months of age, and the heart
is less likely to be severely aected.
There is no cure for Pompe disease,
but medication and therapy can help
manage some symptoms and potentially
slow the course of the disease.
Alglucosidase alfa has been used for ERT for
more than 15 years. It improves ventilator-free
survival as well as cardiac and skeletal muscle
function in patients. Avalglucosidase alfa, which
has similar ecacy to alglucosidase alfa, has
been approved as a second option for ERT.
What is...
Pompe Disease
A Guide for
Individuals and
Families
In general, the later the age of
onset, the slower the progression of
the disease. Ultimately, the
prognosis is dependent upon
the extent of respiratory muscle
involvement.
4
A diagnosis of Pompe disease
can be confirmed by measuring the
level of GAA enzyme activity
in a blood sample, and through
screening for common genetic
mutations.
5
Early detection of Pompe disease
allows for the earliest possible
treatment, which can lead to
better outcomes.
7
Once Pompe disease is diagnosed,
testing of all family members and a
consultation
with a genetic counselor are
recommended.
8
In May 2013, Pompe disease
was added to the list of conditions
that states screen for in newborn
babies, based on the availability
of reliable tests for screening
and diagnosis and of an eective
treatment (enzyme replacement
therapy).
6
What are the signs and symptoms of
Pompe disease?
Pompe disease is a multi-systemic condition, aecting many parts of the body and resulting in
weakness of the skeletal, cardiac (heart), and pulmonary (lung) muscles.
Digestive
Infantile-onset disease:
• Enlargement of the tongue
• Liver impairment
• Poor feeding
• Failure to gain weight
• Failure to thrive
Noninfantile-onset disease:
• Swallowing diculties
• Gastroesophageal reflux
• Diarrhea
• Constipation
Nervous system
• Delayed gross-motor development
Skeleton and muscle
• Muscle weakness
• Generalized muscular
hypotonia (infantile form)
Respiratory system
• Breathing diculties
• Respiratory insuciency
• Respiratory infections
What should I know about Pompe disease?
The infantile-onset form of Pompe
results from a complete or near
complete deficiency of GAA.
Symptoms begin in the first months
of life with feeding problems, poor
weight gain, severe muscle
weakness, “floppiness” (a lack of
muscle tone, called hypotonia), and
head lag. The heart may be
enlarged, and respiratory dicul-
ties are often complicated by lung
infections. Many infants with Pompe
disease also have enlarged tongues
and livers (hepatomegaly). Without
treatment, heart failure
can cause life-threatening compli-
cations by the age of 12
to 18 months. The infantile-onset
form of Pompe can present a
non-classic phenotype; hypotonia
without cardiomyopathy, during the
first one to two years of life.
2
Pompe disease symptom onset may
occur at any time from
infancy to adulthood. It is slowly
progressive and less severe in
its noninfantile-onset forms.
1
Heart (infantile-onset disease)
• Cardiomegaly
• Cardiomyopathy
• Heart failure
Noninfantile-onset Pompe disease
is the result of a partial deficiency
of GAA. Symptoms may begin at any
age. The primary symptom is
muscle weakness, typically in the
legs and trunk, as well as in the
muscles that control breathing,
progressing to life-compromising
respiratory weakness. Problems
with the heart are less likely in this
form of the disease.
3
How is Pompe disease treated?
Treatment for Pompe disease
should involve a multidisci-
plinary team of specialists (such
as a cardiologist, neurologist, and
respiratory therapist) who are
knowledgeable about the disease
and who can oer supportive
and symptomatic care.
A registered dietitian can
suggest well-balanced meals to
help maintain the consumption of
adequate calories and nutrients.
Insertion of a gastrostomy
tube, or g-tube—either
through the nose and down
the throat or surgically
into the stomach— can
deliver food directly to the
stomach or intestines.
Physical therapy helps to
restore and maintain muscle
strength and function
through exercise, as well
as to maintain range of
motion through stretching.
Breathing should be monitored
regularly by a specialist, as
weakened respiratory muscles
make it dicult to cough, leading
to increased risk of serious respi-
ratory infection and pneumonia.
Symptoms such as unusual
shortness of breath on exer-
tion or morning headaches
may indicate compromised
breathing, which may require
supplemental oxygen or ven-
tilatory assistance at night.
A speech or swallowing
therapist can recommend
exercises to strengthen mus-
cles needed for swallowing.
Enzyme replacement ther apy
(ERT) is the approved treatment
for all patients with Pompe dis-
ease. In ERT, a synthetic form of
the maltase enzyme is delivered
to cells to substitute for the en-
zyme missing in Pompe disease.
This may keep muscle cells from
dying. The ERT drugs Myozyme
and Lumizyme were the first
options available to treat infan-
tile-onset and late-onset Pompe
disease, respectively. A second
generation ERT, Nexviazyme,
has also been approved to treat
late-onset Pompe disease.
Since the approval of ERT,
the outlook for people of all
ages with Pompe disease
is better, with reversal
of cardiac damage and
increased life expectancy in
the infantile-onset form of
the disease and improved
respiratory function
and walking endurance
in older individuals.
Cardiomegaly
Enlargement of the heart
Glucose
The simplest carbohydrate, formed from one sugar,
and one of the body’s preferred sources of fuel for
cells — particularly muscle cells
Glycogen
A form of sugar that is stored for future mobilization
and use as energy
Glycogen storage disease
A metabolic disorder, caused by enzyme deficiencies,
that aects the production or breakdown of glycogen
or glucose
Hepatomegaly
Enlargement of the liver
Hypertrophic cardiomyopathy
A condition in which part of the heart muscle
becomes thickened, hindering its ability to pump
blood to the body
Hypotonia
Diminished muscle tone
Macroglossia
Enlargement of the tongue
Mutation
A flaw in the DNA code
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