Name: JOVELYN B. DAHANG Date: FEB.

12,2020
Course/Year/Major:BSED 2ND YEAR-SCIENCE Term/Semester:2ND/ 2ND
Instructor/Professor:PROF. JEMER ALIMBON Permit No.:1342173

Acid Alpha-Glucosidase Deficiency (Pompe Disease): Literature Review and

Case Series

Pompe disease is an autosomal recessive, progressive, debilitating, and often fatal

neuromuscular disorder caused by deficiency of lysosomal acid α-glucosidase (GAA). It is

characterized by the accumulation of glycogen in muscle tissue that leads to progressive

muscle weakness and loss of function. It is happens when your body can't make a protein that

breaks down a complex sugar, called glycogen, for energy. Too much sugar builds up and

damages your muscles and organs. Pompe disease causes muscle weakness and trouble

breathing. It mostly affects the liver, heart, and muscles. (Dasouki, M. et al.)

Researchers have described Pompe disease as an inherited in an autosomal recessive

manner, which means that two copies of an altered (mutated) gene, one inherited from each

parent, is necessary to have the condition. Males and females are equally likely to be affected.

Carrier parents have a 1 in 4 or 25% chance with each pregnancy, to have an affected child, a

50% chance to have a child who is a carrier, and a 25% chance to have a child who is not

affected nor a carrier. Parents who have had a child with Pompe disease are obligate carriers.

Other close relatives may also be carriers depending on their relation to the individual with

Pompe disease. Carriers do not have any health problems as a result of being a carrier.

In the condition of the patient of Pompe disease will experience weakening of the

body muscles. However, muscular dystrophy is a group of inherited diseases in which the

muscles that control movement (called voluntary muscles) progressively weaken. In some forms

of this disease, the heart and other organs are also affected. But, accordingly to the National

Institutes of Health limb girdle one of the example of muscular dystrophy signs and symptoms
may first appear at any age, as observed in Pompe disease and it is just one of the symptoms

similar to Pompe disease, genetic testing is currently available for LGMD but it differs from

Pompe.

Life expectancy in Pompe disease depends on several factors such as the type of

Pompe disease a patient has, the severity of symptoms, and how well they are managed.

Classic infantile-onset Pompe disease is the most severe form of the disease in which

symptoms appear within a few months after birth. Without treatment, affected babies often

succumb to heart disease within their first year of life.

The non-classic infantile-onset form of the disease is comparatively less severe. It

appears within the first year of life and has a slower progression rate, but patients often also

have heart disease and breathing problems, which can be fatal if not attended to in time.

Late-onset Pompe disease can occur at any age. Patients with this type of disease have higher

levels of the acid alpha-glucosidase enzyme than patients with the more severe forms of the

disease. Patients with late-onset disease also show symptoms such as muscle weakness and

breathing problems. They can survive up to age 30 if the disease appears in childhood and up

to age 50 if it develops in adulthood. Generally, the later the age of onset, the slower the

disease progression and the longer the life expectancy. ( Junah M de Vries., et.al).

The trade name of the enzyme designed to replace missing enzyme which deficiency

primarily causes Pompe’s disease is Mannose 6 Phosphate. Accordingly, to the research and

Development Unit, Department of Genetics, the M6P groups are then recognized by two

independent transmembrane M6P receptors, present in the trans-Golgi network: the cation-

independent M6P receptor and/or the cation-dependent M6P receptor. These proteins bind to

lysosomal hydrolases on the lumenal side of the membrane and to adaptins in assembling

clathrin coats on the cytosolic side. In this way, the M6P receptors help package the

hydrolases into vesicles that bud from the trans-Golgi network to deliver their contents to
endosomes that ultimately will develop into mature lysosomes, where recently-delivered

hydrolases may start digesting the endocyted material. The above described process is known

as the M6P-dependent pathway and is responsible for transporting most lysosomal enzymes.

This review synthesizes the current knowledge on each of the major proteins involved in the

M6P-dependent pathway. ( Prata MJ, Alves S )

At this time there is no cure for Pompe disease. There is one FDA approved treatment

called Myozyme which is an enzyme replacement therapy produced by Genzyme

Therapeutics. Enzyme replacement therapy (ERT) works by replacing some of the missing

enzyme in Pompe disease patients’ bodies through lifetime IV infusions of Myozyme every

other week. ERT improves the symptoms of Pompe disease in many patients but not all. In

some patients ERT will decrease heart size, maintain normal heart function, improve muscle

function, tone, and strength, and reduce glycogen accumulation.

Several research studies are working on other types of therapies such as chaperone

therapy, more effective enzyme replacement therapies, and ways to make current enzyme

replacement more effective including small scale gene therapy and immune response

decreasing treatments. Emory participates in several of these clinical trials.

Individuals with Pompe disease are best treated by a team of specialists (such as

cardiologist, neurologist, and respiratory therapist) knowledgeable about the disease, who can

offer supportive and symptomatic care. The discovery of the GAA gene has led to rapid

progress in understanding the biological mechanisms and properties of the GAA enzyme. As

a result, an enzyme replacement therapy has been developed that has shown, in clinical trials

with infantile-onset patients, to decrease heart size, maintain normal heart function, improve

muscle function, tone, and strength, and reduce glycogen accumulation. A drug called

alglucosidase alfa (Myozyme©), has received FDA approval for the treatment of infants and
children with Pompe disease. Another algluosidase alfa drug, Lumizyme©, has been

approved for late-onset (non-infantile) Pompe disease. (Emory University Lysosomal Storage

Disease Center, 800-200-1524)

At the end of the story they are so happy hearing those voices of their children which

emphasizes the “sugar rush” A meta-analysis of carbohydrate effects on mood. However,

Carbohydrates do not have a beneficial effect on any aspect of mood. Analysis revealed no

positive effect of CHOs on any aspect of mood at any time-point following their

consumption. However, CHO administration was associated with higher levels of fatigue and

less alertness compared with placebo within the first hour post-ingestion. These findings

challenge the idea that CHOs can improve mood, and might be used to increase the public's

awareness that the ‘sugar rush’ is a myth, inform health policies to decrease sugar

consumption, and promote healthier alternatives. ( Neuroscience & Biobehavioral Reviews )

As the misconceptions depicted in the movie is that enzyme that being transfer to the

patience was resulted immediately but, accordingly to the researchers that it takes several

infusions to see the results.

In handling this kind of rare disease it can be prevented by genetic counseling which

it is very helpful because Pompe disease is an autosomal recessive so therefore highly

recommended for consulting before achieving a pregnancy to discuss testing options. In

dealing with this disease is that it is how manifest positivity in yourself, accept the fact that it

is the condition that being brought by your parents. Hence, in accepting the reality you will

no longer suffer the situation you have which indicates no matter will happen you can live

with it. As this is a genetic disease it cannot currently be prevented. Supportive treatment and

care are available.

 Living with Pompe disease can be challenging. You and your family may want to see a

counselor to help you come to terms with what's happening, especially as your abilities change. A

support group can also be a safe place to share your feelings and find understanding.

Support groups can be a good source of practical tips, too. For example, if you have

trouble eating, you can try adding thickeners to your food to make it safer to swallow. You might

need to use a feeding tube to make sure you get enough nutrients.

After I watched the movie “extraordinary measures” made me to realize that it is

something to do with how will you accepts the situation. However, it is difficult on how to

treat this kind of diseases but, being as optimistic human being it can’t drive you in suffering

of pain. Moreover, it is somehow difficult to give some remediation but through the help of

experts in dealing with that disease which an individual with Pompe disease needs

specialized medical care from a team of specialists including geneticists, metabolic

specialists/dietitians, cardiologists, pulmonologists, orthopedists, physical, speech, and

occupational therapists, genetic counselors, and neurologists. The combination of specialists

may vary depending on the patient. In addition, a specialized diet and exercise program may

help adult-onset individuals with Pompe disease along with frequent medical evaluations as

the disease progresses.

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Mantantzis, K., Schlaghecken, F., Sünram-Lea, S. I., & Maylor, E. A. (2019). Sugar rush or
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