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How this booklet can help you

This booklet provides information about Pompe disease andhow it is diagnosed and managed. It also offers practical tips on living with Pompe. As you read through thebooklet, keep in mind:

YYoouu aarree nnoott aalloonnee.. There are active patient groups and caring health professionals throughout the world who can help you manage the challenges of living with Pompe disease.

BBeeiinngg iinnffoorrmmeedd ccaann hheellpp yyoouu ttaakkee aa mmoorree aaccttiivvee rroollee iinn yyoouurr ccaarree.. Learning about Pompe disease can help you work with your healthcare team toget the best possible care.

TThheerree iiss rreeaassoonn ttoo bbee hhooppeeffuull.. Over the last several years, there has been a great deal learned about Pompe disease. A phase 2/3 clinical study of the investigational treatment in infantile-onset patients has been completed, and a large clinical trial in late-onset patients is ongoing.

A 2-month-old baby is admitted to the hospital with breathing problems brought on by a bad cold. An x-ray reveals a greatlyenlarged heart.

A 2-year-old child who has just startedwalking has an odd walk that is a crossbetween a waddle and a limp. As aninfant, he had trouble turning over andholding up his head.

A college student becomes winded and her muscles ache when she climbs a flight of stairs.

All of these people have Pompe disease.

This rare inherited muscle disease shows

up in different ways in children and adults of

all ages. If you or your child has been diag-

nosed with Pompe disease, it can be difficult to

imagine how the disease will affect your

health or the health of those you care for.

And because the disease is rare, it is not easy

to know where to turn for information, guid-

ance, and support. We hope that gaining a

better understanding of Pompe disease will

help you find strength as you begin to move

from diagnosis to action.

What’s inside:

What is Pompe disease? 2

How is Pompe disease diagnosed? 8

How is Pompe disease managed? 15

What can I do to make it easier to live with Pompe disease? 25

Where can I find more information and support? 30

These are somefaces of Pompedisease

The information in this booklet is not meant to take the place of professional medical advice. Always discuss your questions and concerns with your healthcare provider.

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Pompe disease goes by many different names: ■ Acid alpha-glucosidase deficiency

■ Acid maltase deficiency (AMD)

■ Glycogen storage disease (GSD) type II

■ Glycogenosis II

■ Lysosomal alpha-glucosidase deficiency

NNOOTTEE:: In scientific articles, the enzyme acid alpha-glucosidase may be written as acid α-glucosidase or shortened to α-glu or AGLU. It is also commonly shortened to GAA. GAA actually stands for glucosidase acid alpha, which is the name given to the gene(not the enzyme).

What are the symptoms of Pompe disease?Progressive muscle weakness is the most common symptom of Pompe disease. The muscles most often affected are those used for breathing andmobility (the ability to move around). In many infants, the heart muscle isseverely affected.

PPoommppee ddiisseeaassee iiss oofftteenn bbrrooaaddllyy ddiivviiddeedd,, oorr ccllaassssiiffiieedd,, iinnttoo 22 ggrroouuppss.. Children withinfantile-onset Pompe disease usually show symptoms of the disease during the first few months of life. This classic form of infantile-onsetPompe disease progresses rapidly and is almost always fatal before the age of 1year. Some children have a nontypical form of infantile-onset Pompe disease, inwhich symptoms show up later in the first year of life. In these children, damageto the heart muscle progresses more slowly, and they may survive beyond theirfirst birthday.

Children and adults whose symptoms show up after 1 year of age may receive adiagnosis of late-onset Pompe disease. The late-onset form of the disease tendsto progress more slowly than the infantile-onset form but can present significantchallenges as muscle weakness increases. There is no data currently available tosuggest mental development is affected ineither form of the disease. About one third of all people born with Pompe dis-ease have the infantile-onset form while roughly two thirds have the late-onsetform.

How many people have Pompe disease?It is thought that there are between 5,000 and 10,000people around the world living with the symptoms ofPompe disease. As with many rare diseases, it is difficult to know exactly how many peo-ple are actually affected. Based on studies done inthe Dutch population and in New York City, it is esti-mated that Pompe disease occurs in 1 in 40,000 livebirths worldwide.

Pompe disease affects both men and women equally. Itoccurs in all ethnic groups but does appear at a higherrate in the African American population, as well as in Southern China and Taiwan.

Dr. J.C. Pompe

What is Pompe disease?Pompe disease is a rare neuromuscular disorder that occurs in babies, children, and adults who inherit a defective gene from their parents. It is one of more than 40 genetic diseases that are known as lysosomal storage disorders. Pompe is a progressive disease, which means it gets worse over time.This makes it similar to other neuromuscular disorders, such as the muscular dystro-phies. They also cause progressive muscle weakness and loss of muscle tissue(muscle wasting). Because the muscle weakness occurs as a result of changes thattake place inside the body’s cells, Pompe is also a metabolic muscle disease. It is also considered a glycogen storage disease. This is becausethe changes are a result of a buildup of glycogen (GLY-co-jen) in muscle cells.

Pompe disease is named after J.C. Pompe, the Dutch doctor whofirst described the disorder in 1932 after observing an infant withsevere muscle weakness and a greatly enlarged heart. There areseveral ways to pronounce the name of the disease. In differentparts of the world, you may hear “pom-PAY,” “POM-puh,” or “pom-PEE.”

Pompe diseaseaffects people fromaround the world

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What causes Pompe disease?In people with Pompe disease, there is a defect in a gene named GAA. This gene is responsible for making an enzyme called acid alpha-glucosidase(AL-fa glue-CO-sih-days) within the lysosome, a compartment in the cell.Enzymes are proteins that do specific jobs to help keep the cells in the body workingnormally. The job of acid alpha-glucosidase is to break down glycogen, a form ofsugar stored in muscle cells throughout the body. In people with Pompe disease,this enzyme is either missing or in short supply.

LLyyssoossoommeess are compartments inside each cell where glycogen is broken down.

In Pompe disease, the buildup of glycogen causes the lysosomes to expanduntil they take up so much space thatthe muscle cell is damaged.

GGllyyccooggeenn begins to leak out of the lyso-somes and cause more damage to thesurrounding muscle cells. This leads tomuscle weakness that gets worse overtime.

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The spectrum of Pompe diseaseThough the genetic defect that causes Pompe disease is present at birth, symp-toms may show up at any time from infancy through adulthood. In fact, one ofthe most striking features of the disease is how much it varies from one personto another in terms of:

■ The age at which symptoms first appear

■ The rate at which the disease progresses

■ The degree to which other organs are affected

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Infantile Onset

Level of Enzyme Activity

Late Onset

Enzy

me

Act

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y (%

of N

orm

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25

0

40

IInn ggeenneerraall,, tthhee eeaarrlliieerr ssyymmppttoommss sshhooww uupp,, tthhee mmoorree sseevveerree tthhee ddiisseeaasseeiiss lliikkeellyy ttoo bbee.. The disease progresses rapidly in infantile-onset patients whohave little or no enzyme activity.

By contrast, Pompe disease tends to progress more slowly in childrenand adults with late-onset disease who have at least a small amount of acid alpha-glucosidase activity.

This graph shows the level of acid alpha-glucosidase enzyme activity in the 2 forms of Pompe disease. Pompe disease is typicallymore severe in people who have lower levels of activity.

Normal muscle fiber (cell)

Affected muscle fiber (cell)

Skeletal muscle

Bundle of muscle fibers

Affected Individuals (25%)

Unaffected Carrier (25%)

Unaffected Carrier (25%)

Unaffected Individuals (25%)

Children

Mother Carrier

Father Carrier

Parents

Autosomal Recessive Inheritance

= Normal gene

= Abnormal (defective) gene

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If both parents are carriers:■ There is a 1 in 4 chance that the child will inherit 2 normal copies of

the gene and bbee uunnaaffffeecctteedd

■ There is a 2 in 4 chance that the child will inherit an abnormal copy from 1 parent and a normal copy from the other parent and bbeeccoommee aa ccaarrrriieerr.. Carriers will not develop Pompe disease but may passon 1 defective gene to their children

■ There is a 1 in 4 chance that the child will inherit 2 abnormal copies ofthe gene and ddeevveelloopp PPoommppee ddiisseeaassee

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How do you get Pompe disease?Pompe disease is inherited through our genes. The genes are made from DNA, thechemical material that contains the instructions for every process in the humanbody and every other feature that makes us unique. Ourgenes are arranged on 23 pairs of chromosomes. One of those pairs (called sex chromosomes) determines whether a person will be male or female. The other 22 pairs (called autosomes) determine traits that are not related to a person’s sex, such as eye color and height. Pompe disease affects males andfemales equally because it is inherited through a gene that is carried on one of the 22 pairs of autosomes.

Some genes contain codes for making the enzymes that help the body function. If there is a mutation, or change, in a gene responsible for making a specific enzyme,then that enzyme may not work properly or may not be made. In Pompe disease, there are mutations in the gene for acid alpha-glucosidase.Pompe disease is an autosomal recessive disorder. This means you only get it if you receive 2 copies of the defective GAA gene — 1 from each parent. KnownPompe mutations can be identified using genotype testing, which examines the DNA in a blood sample. This is sometimes done when Pompe disease is suspected or when a presumed diagnosis has been made but not confirmed and may also be done when there is a family history of Pompe disease.

Inheriting the geneThe chart on the next page shows what can happen if both parents are carriers of the defective gene. With each pregnancy, there is a 25% chance thatthe child will develop Pompe disease.

OOtthheerr ppoossssiibbllee ssiittuuaattiioonnss■ If 1 parent has Pompe disease and the other is not a carrier,

then all children will be carriers (and none will develop the disease)

■ If 1 parent has Pompe disease and the other is a carrier (a very rare situation), then there is a 50% chance of having a child who will develop the dis-ease and a 50% chance of having a child who is a carrier

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How is Pompe disease diagnosed? Diagnosing Pompe disease can be challenging because many of the symptoms aresimilar to those of other diseases. In addition, symptoms often develop slowly andmay not show up at the same time. It may be easier to diagnose the infantile-onset form of Pompe disease because the rapid progression and more pronounced symptoms may prompt healthcare providers to perform moreextensive testing. Many healthcare providers, though, have never seen a patientwith Pompe disease. In most cases, healthcare providers have to rule out othermore common possible causes before considering a diagnosis of Pompe disease. Ifa patient complains only of breathing problems — or only of muscle weakness —Pompe disease may be overlooked. The patient may then receive another diagnosis, such as carnitine deficiency, hypothyroidism, orlimb-girdle muscular dystrophy.

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■ Primary care physicians

■ Pediatricians and developmentalpediatricians

■ Neurologists

■ Pulmonologists

■ Cardiologists

■ Metabolic specialists

■ Geneticists

■ Emergency room specialists

Medical specialists who assist in diagnosis

If there are no specialists in your area who are familiarwith Pompe disease, ask your family doctor to refer you to a major medical center that is known for diagnosing rare diseases. If the nearest center is too far away, urge your doctor to consult with an expert there about how to handle your case. As many people with Pompe and other rare diseases have learned, it is important to work closely with your healthcare provider to make sure you get the best care possible.

Tests that confirm the diagnosisA number of tests may be done to help diagnose Pompe disease and deter-mine the extent of muscle weakness or how far the disease has progressed. However, an enzyme assay is commonly used to confirm a diagnosis of Pompe disease. This biochemical test measures the activity ofacid alpha-glucosidase in a small sample of skin, muscle, or blood. The enzymeassay may be performed using different samples. These include:

■ Cultured skin fibroblasts ■ Lymphocyte (blood)

■ Muscle ■ Dried blood spot (not yet available; underinvestigation in the United States)

A diagnosis of Pompe disease is confirmed if the test shows there is less thannormal or no enzyme activity. You may find regional differences in the avail-ability of these tests and how healthcare professionals use them to diagnosePompe disease.

Other clinical tests that may be performed Healthcare providers may also order other tests. These tests may pointtoward a muscle disorder or detect which muscles and organs may beaffected and to what extent. These tests may include:

■ BBlloooodd tteessttss to check the level of creatine kinase (CK), an enzyme that isreleased at higher levels when muscle injury occurs

■ EElleeccttrroommyyooggrraapphhyy (ee-LEK-tro-my-AH-graph-ee) (EMG), a test thatrecords electrical activity in affected muscles (but may show a normalpattern in some people with late-onset Pompe disease)

■ A cchheesstt xx--rraayy,, often performed in infants to see if the heart is enlarged

■ An eecchhooccaarrddiiooggrraamm (eh-co-CAR-dee-oh-gram) or echo test, an ultrasoundthat can show if the heart muscle has become too thick or is not func-tioning properly

■ An eelleeccttrrooccaarrddiiooggrraamm (ee-LEK-tro-CAR-dee-oh-gram) (EKG) that candetect abnormal patterns of heartbeats and electrical activity

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Infantile-onset Pompe diseaseInfantile-onset Pompe disease is a life-threatening condition that affects all of the major body organs. The chart below lists the major symptoms.Without a disease-specific treatment, the disease progresses rapidly. The infantmay quickly become gravely ill. Babies with infantile-onset Pompe disease are notlikely to survive past the age of 1 year.

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What are the different forms of Pompe disease?

Pompe disease shows up in different ways in children and adults of all ages. AA 33--mmoonntthh--oolldd bbaabbyy who seemed “normal” at birth is diagnosed with an enlarged heart. At 6 months he cannot sit up without support. Tests confirmthe baby has infantile-onset Pompe disease. He becomes very weak and needs a feeding tube to help him gain weight. Even with his physical problems, he is a happy baby who greetseveryone he sees with bright eyes and a smile.

AA 66--yyeeaarr--oolldd is having trouble climbing the stairsand doesn’t have the energy to make it through gym class. After many tests, she isdiagnosed with late-onset Pompe disease. Thoughshe is too weak to play catch, she is able to ride a bicycle all through her childhood. In her twenties, her muscles becomeso weak that she must trade the bicycle for an adapted car — and a wheelchair. Rather than dwell on the loss of mobility, she sees the wheelchair as a way to stay active and independent.

AA 3377--yyeeaarr--oolldd mmaann suddenly starts falling asleepduring the day and has trouble breathing when he is lying down. After 2 years of being tested and examined by different healthcare providers, he is diagnosed withlate-onset Pompe disease. Looking back, he canrecall that even though he was active in sports as achild, he could never quite keep up with the otherkids on the team. He now uses a ventilator atnight to help with his breathing problems. He isstill driving and enjoys working full-time.

Major symptoms of infantile-onset Pompe disease

MMuusscclleess

■ Severe muscle weakness

■ “Floppiness” due to loss ofmuscle tone

■ Head lag — when you try to pull the baby up to a sitting position by grasping thehands or arms, the head drops back

■ Frog-like position of legs

■ Failure to meet developmentalmilestones such as rolling over,sitting up, crawling, and walking — or loss of mile-stones

LLuunnggss

■ Difficulty breathing

■ Frequent respiratory infections

■ Respiratory failure

DDiiggeessttiivvee ((GGII)) TTrraacctt

■ Feeding problems that occur asit becomes harder to breathe,suck, or swallow

■ Failure to thrive or gain weightas rapidly as other babies thesame age

■ Enlarged liver

■ GI discomfort: vomiting, regur-gitation

■ Enlarged tongue

HHeeaarrtt

■ Enlarged heart

■ Heart failure

■ Heart rhythm changes

Pompe disease variesfrom person to person

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What are some of the common health problems of Pompe disease? Muscle weakness can lead to many different health problems. Yet not all people with Pompe disease have the same problems. For some, the impactwill be severe. For others, it will be milder. In either case, when medical prob-lems occur, it can be hard to realize that they could be related to Pompe disease. But if one knows what to expect, he or she will be better able to seek medical care that is tailored to specific needs. KKeeeeppiinngg ttrraacckkooff ssyymmppttoommss aanndd ggeettttiinngg rreegguullaarr cchheecckkuuppss ccaann aallssoo hheellpp pprreevveenntt hheeaalltthh pprroobblleemmssffrroomm bbeeccoommiinngg mmoorree sseerriioouuss..

BBrreeaatthhiinngg pprroobblleemmss mmaayy ddeevveelloopp sslloowwllyy oorr ccoommee oonn ssuuddddeennllyy.. Pompe disease weakens the diaphragm, one of the main muscles used for breathing (located just below the lungs and above the abdomen). It can be hard to breathe deeply, especially when lying on the back. Patients may feel short of breath and have trouble sleeping soundly. Patients may getmorning headaches. It may also be hard to cough strongly enough to clear mucus from the lungs. This increases the risk for lung infections such aspneumonia.

Prolonged shallow breathing can result in respiratory insufficiency. This is a condition that occurs when reduced airflow into the lungs causes carbon diox-ide to build up in the blood. This may cause shortness of breath, morning headaches, or sleep problems. It may make it hard to function during the day. Respiratory insufficiency increases the risk for developing chestinfections and respiratory failure, which means patients cannot breathe on theirown. SSeeeekkiinngg ttrreeaattmmeenntt aatt tthhee ffiirrsstt ssiiggnn ooff bbrreeaatthhiinngg pprroobblleemmss ccaann hheellpp pprreevveenntttthhiiss mmeeddiiccaall eemmeerrggeennccyy..

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Late-onset Pompe diseaseLate-onset Pompe disease tends to progress more slowly than the infantile-onsetform. Symptoms and severity can vary widely from one person to another. Thechart below describes the major symptoms. Major breathing problems, such as res-piratory failure, can shorten the life span of individuals with late-onset Pompe dis-ease. But many are able to adapt to the challenges that the disease presents andcontinue with their lives.

Major symptoms of late-onset Pompe disease

MMuusscclleess

■ Progressive muscle weakness inthe legs and hips

■ Difficulty climbing stairs, running, or getting up from a chair

■ Walking with swaying hips or awaddle

■ Frequent trips and falls (loss of balance)

■ Gradual loss of motor milestones that have beenachieved, such as walking, run-ning, or jumping (children)

■ Low back pain

■ Scoliosis (curvature of the spine)

LLuunnggss

■ Difficulty breathing, especiallyafter exertion or when lying onyour back

■ Morning headaches, daytimesleepiness, shortness of breathand other signs of respiratoryinsufficiency

■ Frequent respiratory infections, such as bronchitisand pneumonia

DDiiggeessttiivvee ((GGII)) TTrraacctt

■ Difficulty gaining or maintaining weight

■ Problems chewing and/or swal-lowing

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How is Pompe disease managed? For now, medical problems that arise are managed with supportive care. This is arange of services delivered by a team of health professionals. These therapies canease the burden of living with Pompe disease by helping people with Pompe disease feel better emotionally and physically.Investigational treatment that aims to replace the missing enzyme is being stud-ied in clinical trials. Even when treatment becomes available, supportive care will continue to be an important part of Pompe disease manage-ment. It is important for patients to work with their healthcare team to find thespecific therapies that may offer the most value.

A team approach to supportive care

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WWeeaakk mmuusscclleess ccaann ccaauussee eeaattiinngg pprroobblleemmss.. Pompe disease can weaken the muscles used for biting, chewing, and swallowing food. Infants who are very weak may not be able to suck from a breastor bottle. In infantile-onset disease, vomiting or regurgitation (when swallowedfood mixes with stomach acids and flows back toward the throat) may also occur.

Eating problems may also prevent patients with late-onset Pompe disease from get-ting the nutrition their bodies need. They may lose weight or have trouble keepingit on. If breathing problems disrupt sleep, patients may lose their appetites or be too tired to eat.

WWeeaakknneessss ooff tthhee sskkeelleettaall mmuusscclleess ccaann lleeaadd ttoo mmoobbiilliittyy pprroobblleemmss.. Pompe disease weakens muscles throughout the body that enable patients to walk, keep their balance, stand up straight, and move freely. Increasing weak-ness and lack of muscle use can make muscles stiff and tight, which can bepainful. Extra stress on joints and ligaments may also cause muscle aches andlower back pain. If muscles or tendons get too tight, they can “freeze” or become fixed in one position, forming a contracture. This can prevent normal movement. Muscle weakness may also lead to the development of scolio-sis, a sideways curvature of the spine, which, in severe cases, can make it harder tobreathe.

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CARE COORDINATOR

Cardiology and pulmonology care visits

Psychosocial therapy

Respiratorytherapy

Genetic counseling

Physical therapy

Speech therapy

Nutritional anddietary therapy

Occupational therapy

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Types of supportive care

RReessppiirraattoorryy tthheerraappyy Respiratory therapy can provide the critical support needed to manage breathing problems. A respiratory therapist can teach exercises to strengthen breathing muscles. As the muscles used for breathing get weaker, mechanical ventilation may be needed. Mechanical

ventilation uses machines that support breathing by sending air to the lungs. Itmay be provided in 1 of 2 ways.

NNoonniinnvvaassiivvee vveennttiillaattiioonn may be used to manage early-stage breathing problems. Portable machines supply air through a mask that fits over the nose orboth the nose and mouth. At first, a ventilator may be needed only at nightwhile you sleep. As breathing problems become more severe, the ventilator maybe needed during the day as well.

Two types of noninvasive ventilators are often recommended for people withPompe disease. They are bilevel airway pressure (BiPAP) ventilators and continu-ous positive airway pressure (CPAP) ventilators. Both allow you to vary theamount of air delivered to the lungs while you inhale. This way, your musclesare still doing some of the work of breathing. CPAP ventilators provide positivepressure that is constant when a patient inhales and exhales. This can requiremore work for the muscles to exhale. For people with Pompe disease, the CPAPmachine is generally used to treat sleep apnea (when breathing stops for shortperiods during sleep).

IInnvvaassiivvee vveennttiillaattiioonn provides more intensive respiratory support to infants, chil-dren, and adults. It is used when a serious lung infection or worsening breathingproblems result in respiratory failure. In these emergency situations, there is oftenan urgent need to get air into the lungs as quickly as possible. This may be donemanually by inserting a tube directly into the windpipe through the mouth ornose, called intubation (in-too-BAY-shun). It may also be done surgically byinserting the tube into the windpipe. This procedure is called a tracheostomy (tray-key-OSS-toe-me). The breathing tube isthen connected to a ventilator that provides breathing support.

The information in this booklet is not meant to take the place of professional medical advice. Always discuss your questions and concerns with your healthcare provider.

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Development of standards of care Standards of care are guidelines for healthcare providers to follow when diagnosing and treating diseases. These guidelines can help ensure earlier diagno-sis and aid in managing a disease like Pompe. They can also help patients receivemedical care tailored to the disease and get better follow-up care. Two professionalgroups are working on developing standards of care for Pompe disease. TheAmerican College of Medical Genetics (ACMG) has proposed draft guidelines forscreening inherited metabolic disorders in newborns and children. The European Neuromuscular Center (ENMC) is developing standards of care to diagnose, monitor, and manage Pompe disease in infants, children, and adults. Genzyme’s Pompe Community Web site(www.pompe.com) will provide information regarding these developments in Pompedisease management as it becomes available.

Play an active role to help get the care you needYou may find that many healthcare providers have never heard of Pompe dis-ease. And those who offer supportive care may not know how to meet yourspecific needs. If that’s the case, it may take additional steps to get the kind of care you need. Here are some steps you can take:

■ RReeaacchh oouutt ttoo PPoommppee ppaattiieenntt oorrggaanniizzaattiioonnss oorr tthhee MMuussccuullaarr DDyyssttrroopphhyyAAssssoocciiaattiioonn for information, resources, and support. They can suggesttherapists in your area who have been trained to treat neuromuscular disorders

■ TTrryy ttoo lleeaarrnn aass mmuucchh aass yyoouu ccaann aabboouutt PPoommppee so that you can ask your healthcare providers about therapies that might be helpful for you

■ CCoonnttaacctt GGeennzzyymmee (see page 32) to request free copies of this booklet and A Physician’s Guide to Pompe Disease. These resources areavailable to members of your healthcare team who may not be familiarwith Pompe disease

This active role may not be familiar to you, but it is the kind of role that maybe helpful when you are affected by a rare disease like Pompe. (For moresuggestions on how to obtain care for Pompe disease, see page 20.)

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PPhhyyssiiccaall tthheerraappyyPhysical therapy can improve balance, posture, and muscle tone; support mobility; maintain flexibility and

range of motion; and ease muscle painand stiffness. The goal is to help people stay healthy, strong, and mobile.The therapy may include the use of exercis-es, massage, machines, and adaptive devices such as foot splints orwheelchairs. Stretching exercises canimprove a young child’s posture and helpprevent contractures (muscle tightness).The physical therapist can help peoplelearn new ways to sit, stand, or movearound as muscle weakness progresses. The therapist can also teach people how to use different muscles to do the work of muscles they can no longer use.

OOccccuuppaattiioonnaall tthheerraappyyOccupational therapy helps people with muscle weakness learnnew ways to complete daily tasks at home, in school, and atwork. The therapy may consist of specific exercises to helpmaintain strength and dexterity (the skill and ease with whichyou use your hands). It can teach how to use

adaptive devices that make it easier to do activities of daily living (such as bathing, dressing, and cooking), participate in school activities, or perform job duties. Occupational therapists may also recommend special equipment or changes that can be made in the classroom or workplace to help people with progressive muscle weakness function well in these environ-ments.

The information in this booklet is not meant to take the place of professional medical advice. Always discuss your questions and concerns with your healthcare provider.

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DDiieettaarryy tthheerraappyyIf you have eating problems that make it hard to maintain a healthy weight, a registered dietitian

can help you plan well-balanced meals to get the calories and nutrients you need.To help prevent muscle wasting in patients with late-onset Pompe disease,doctors may prescribe a high-protein, low-carbohydrate diet. This diet is high inmeats, poultry, and fish and low in breadsand starchy foods. This type of dietary thera-py has not been shown to provide consistentresults. Some children and adults have hadimprovements in lung function and musclestrength after following a carefully supervised high-protein diet. For others, the benefits havebeen modest at best. Combining a high-pro-tein diet with daily exercise (also carefullysupervised) may produce better results. Always consult your healthcare provider before beginning any diet or exercise program. Some studieshave suggested that adding alanine, an amino acid (one of the building blocks of protein), to the diet may also be helpful.

Tube feeding may be required for infants who are not gaining weight or for childrenand adults who are severely underweight or have serious swallowing or breathingproblems. Liquid food is carried directly to the stomach or intestines. This can bedone through a nasal tube that goes through the nose, throat, and esophagus or bya gastrostomy (gas-TROSS-toe-me) tube, or G-tube, that is surgically attached to the stomach wall. Another option is a gastrojejunostomy (GAS-troh-jee-ju-NOSS-toe-me) tube, or G-J tube,that is attached to the small intestine.

AA ppaattiieenntt eexxppeerriieennccee::A 27-year-old womandiagnosed with late-onset Pompe diseasealways had trouble gaining weight. Butafter starting a special dietand exercise programsupervised by a metabolic specialist, her health improved dramatically. The extranutrition she gets fromovernight tube feedinghelps keep the weighton and gives her moreenergy to get throughthe day.

AA ppaattiieenntt eexxppeerriieennccee::A 13-year-old with late-onset Pompe disease is showing signsof scoliosis. He exercis-es with a physical thera-pist to help strengthenhis muscles and hope-fully delay the need fora wheelchair. He alsokeeps up his strength by playing tennis andswimming.

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The medical specialists who may be involved in your care have a wide range of skills. In addition to the healthcare professionals who provide supportive care, your careteam may include the specialists listed below.

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How do I find medical care for Pompe disease?Your primary healthcare provider or yourchild’s pediatrician may recommend that yousee a Pompe disease medical expert. Buthow do you find one? Few medical centersspecialize in the management of Pompe disease. And there may be a limitto how far you are willing or able to travel toget care. But you may be able to obtain expert care close to home. Manyclinics and rehabilitation centers treat neuro-muscular disorders that are similar to Pompedisease, such as muscular dystrophy (MUSS-cue-larr DISS-tro-fee). There are also a number of medicalcenters at major universities that specializein caring for patients with rare genetic diseases.

CCoommpprreehheennssiivvee ccaarree cceenntteerrss ccaann ooffffeerr aa rraannggee ooff sseerrvviicceess iinn oonnee ppllaaccee

Many of these facilities also participate in clinical trials to evaluate an investigational treatment for Pompe disease.

■ Genetic screening and counseling

■ Diagnostic procedures, such as muscle biopsy or enzyme level testing

■ Lab tests

■ Sleep studies

■ Early intervention fordevelopmental delays

■ Visits with specialists, such as car-diologists, pulmonologists, andneurologists

■ Supportive therapy to managesymptoms

■ Regular checkups

■ Flu vaccines

■ Support groups

■ Help with insurance claims

CCaarree ccoooorrddiinnaattoorr

This healthcare provider takes the lead in planning and arranging for testsand disease management. This person may be a primary care physician,a pediatrician, or a specialist.

EExxppeerrttss wwhhoo ddiiaaggnnoossee aanndd ttrreeaatt mmeeddiiccaall pprroobblleemmss ccaauusseedd bbyy PPoommppee ddiisseeaassee

■ NNeeuurroollooggiisstt oorr ppeeddiiaattrriicc nneeuurroollooggiisstt:: diagnoses and treats neuromuscular problems

■ CCaarrddiioollooggiisstt:: monitors and treats heart problems

■ PPuullmmoonnoollooggiisstt oorr rreessppiirraattoorryy ssppeecciiaalliisstt:: monitors and treats breathing problems

■ GGeenneettiicciisstt//mmeettaabboolliicc ssppeecciiaalliisstt:: diagnoses and counsels family membersabout genetic diseases

■ GGaassttrrooeenntteerroollooggiisstt:: treats digestion and feeding problems

■ OOrrtthhooppeeddiisstt:: treats joint and bone problems, such as scoliosis and contractures

PPrroovviiddeerrss wwhhoo aaddddrreessss ppssyycchhoossoocciiaall aanndd pprraaccttiiccaall nneeeeddss

■ SSoocciiaall wwoorrkkeerr oorr ppssyycchhootthheerraappiisstt:: offers emotional support and assists with practical matters or financial concerns

■ GGeenneettiicc ccoouunnsseelloorr:: provides guidance on genetic issues, such as family planning, carrier testing, and prenatal screening

TIPTo help locate comprehensive care centers for neuromuscular disorders or genetic diseases, see pages 30-32.

If you do not have access toa center, you might contactspecialists at one of thesecenters and ask them toconsult with your localhealthcare providers byphone or e-mail. Or askyour local healthcareproviders to contact thespecialists on your behalf.

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Current status of ERT clinical trials■ More than 140 people around the world are receiving the investigational

enzyme through clinical studies or expanded access programs to evaluate thesafety and/or effectiveness of rhGAA (recombinant human acid alpha-glucosi-dase)

■ In an expanded access program, patients who do not qualify for a clinical trial are able to receive the investigational enzyme. These programs are generally managed by the manufacturer of the drug and not the researchers who are managing the investigational clinical trial

■ If you have questions about enrolling in clinical trials or expanded access pro-grams for Pompe disease (see Resources available from Genzyme on page 32),contact the Medical Information department at Genzyme

FFoorr mmoorree iinnffoorrmmaattiioonn oonn cclliinniiccaall ttrriiaallss,, yyoouu ccaann ggoo ttoo wwww..cclliinniiccaallttrriiaallss..ggoovv aannddsseeaarrcchh ffoorr ““PPoommppee”” wwhheerree yyoouu wwiillll ffiinndd aa lliisstt ooff aaccttiivvee aanndd ccoommpplleetteedd ttrriiaallss ffoorrPPoommppee ddiisseeaassee..

Gene therapyWith gene therapy, scientists hope to insert a normal copy of the GAA gene into the body so that it would be able to start making acid alpha-glu-cosidase on its own. So far, preclinical research (using animals) has focused onfinding the best vehicle to transfer the gene into the body and reach the cells that will make enough enzyme to start clearing away glycogen and restoring muscle function. If this effort succeeds, it would be a major advance in the treatment of Pompe disease. Gene therapy is still in its early stages, and testing has not yet begun in humans.

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Is there treatment for Pompe disease?Investigational therapeutic approaches to Pompe disease are now being studied at research centers around the world. These include enzyme replacement therapy and gene therapy. Before a new therapy can be approved foruse by people with a particular disease, it must be thoroughly tested in formalresearch studies. These are referred to as preclinical studies (animal) and clinicaltrials (human). The studies progress from those using animals to the clinical trials in humans, which are conducted in phases (1 to 3). Each clini-cal trial phase is designed to evaluate the safety and/or effectiveness of the treat-ment by giving it to groups of patients for a set period of time to see how the treatment affects their health. In order to obtain approval for the treat-ment, the data from all of these studies (preclinical and clinical) must be carefully reviewed by government regulatory agencies.

Enzyme replacement therapy (ERT)This investigational treatment aims to replace acid alpha-glucosidase that people with Pompe disease cannot make on their own. It is called a recombinant, or geneticallyengineered, enzyme. ERT is given to patients asan investigational treatment through an intravenous (IV) infusion (an injection given over time directly into a vein).

Studies to evaluate the safety and effectiveness ofERT have been under way for several years and arecurrently ongoing. Initial clinical trials looked at patients with infantile-onset Pompedisease and a small number of severely affectedpatients with late-onset disease. However, a clini-cal trial of ERT with a larger number of late-onsetpatients is now being done. The results of these studies will help deter-mine the overall safety and effectiveness of thistherapy.

Treatment for people with Pompe disease maybe available in thenear future

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What can I do to make it easier to live withPompe disease? Pompe disease is a chronic neuromuscular disease that causes changes over time.Because Pompe affects everyone differently, it is hard to predict how these changesmay affect your day-to-day life. Though you will surely find your own ways tocope with issues that arise, there are a number of strategies and sources of supportthat have helped people with other neuromuscular diseases adapt to the kind ofchallenges you may encounter. The advice presented on the next few pages comes from Pompe patient advocates, familymembers, and professionals who understand the needs of people living with chron-ic neuromuscular diseases. Though not every tip suggested here may apply toyour situation, some may be helpful to you as time goes by. Also turn to pages 30to 32 for more resources.

Suggested strategies for helping children who are living with chronic muscular diseases■ HHeellppiinngg yyoouurr cchhiilldd bbee aass iinnddeeppeennddeenntt aanndd aaccttiivvee aass ppoossssiibbllee.. Giving

children the chance to do tasks, chores, and activities that are tailored to their age and abilities can help them feel better about themselves. At every age, it may help to encourage involvement in sports, art, and musicprograms that meet your child’s need for social interaction and physical activity

■ LLeeaarrnniinngg hhooww ttoo aaddvvooccaattee ffoorr yyoouurr cchhiilldd’’ss ssppeecciiaall nneeeeddss.. For example, work withyour child’s school to set up an Individual Educational Program (IEP). This typeof plan spells out the services the school must provide for your child, such as apersonal aide, special equipment, or adaptive physical education activities

■ TTaakkiinngg ssoommee ttiimmee ffoorr yyoouurrsseellff.. If you are caring for someone with Pompe disease, it is very important for you to take breaks from caregiving.Finding someone reliable and trustworthy to provide care for a short time mayreduce stress and allow you to renew your energy. If your child needs round-the-clock care, it is also important for you to be realistic about how much of thecaregiving you can handle by yourself

Clinical trialsFor a rare disorder like Pompe disease, a clinical trial may give patients the chanceto try an experimental treatment that they may not have access to otherwise. Tojoin a clinical trial, the volunteer patients must meet certain enrollment criteriabased on their age, gender, the stage and severity of their disease, and other fac-tors. The clinical investigator or doctor running the study must explain both therisks and possible benefits of the trial before volunteers can agree to participate. Volunteers must then sign a document calledan Informed Consent Form, in which they acknowledge that they have been advisedof the risks and benefits and voluntarily agree to participate in the trial. Patientscan withdraw from such a trial at any time. This process of informed consent andother rules are in place to help protect the health and safety of patients.

FFiinnddiinngg cclliinniiccaall ttrriiaallssFor up-to-date additional information about Pompe disease research studies throughout the world that are actively recruiting volunteer patients, visit www.clini-caltrials.gov, the US government clinical trial Web site run by the National Library of Medicine (NLM). Enter “Pompe” in the search area. If you do not have access to the Internet, you may call NLM at 1-888-346-3656 (toll free in the United States) or 1-301-594-5983 (from outsidethe United States).

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WWoorrkk aanndd ssoocciiaall aaccttiivviittiieess■ FFiinnddiinngg wwaayyss ttoo kkeeeepp wwoorrkkiinngg iiff iitt iiss iimmppoorrttaanntt ttoo yyoouu.. As your physical

abilities change, your employer may make accommodations that will helpyou in doing your job. For ideas about what kind of accommodations wouldbest meet your needs, visit the Web site of the Job Accommodation Network (www.jan.wvu.edu) and click on“Individuals with Disabilities”

■ KKeeeeppiinngg uupp yyoouurr ssoocciiaall lliiffee.. As much as possible, try to spend some of your day enjoying hobbies or interests and being with people you like. Ifyou cannot do a hobby as well as you used to, see if you might be able todo it differently. Or try new activities that use the skills and strengths you still have

SSuuppppoorrtt ffrroomm ootthheerrss■ LLeeaarrnniinngg ttoo aasskk ffoorr hheellpp.. Ask family, friends, and neighbors for

help with specific tasks like taking you to your healthcare provider, goingshopping, or keeping your child company for an hour or 2 each week. Let others know you need their companionship, too

■ BBuuiillddiinngg aa nneettwwoorrkk ooff ssuuppppoorrtt.. In addition to your circle of friends and family, reach out to religious groups, government and social service agencies, and healthcare providers in your local community who maybe able to help you get home healthcare, equipment, financial assistance, transportation, or other services

■ SSeeeekkiinngg oouutt ootthheerr ppaattiieennttss aanndd ffaammiilliieess ooff ppeeooppllee wwiitthh PPoommppee ddiisseeaassee ffoorr eennccoouurraaggeemmeenntt aanndd aaddvviiccee.. There are patient organizations around theworld that can help you connect with people in your area (see resources onpages 30 to 32)

Suggested strategies for adults living withchronic neuromuscular diseasesTrying to balance your emotional, social, physical, and financial needs canbe stressful. These strategies can help you reduce stress and put your energy intoliving as well as you can.

EEmmoottiioonnaall hheeaalltthh■ CCaarriinngg ffoorr yyoouurrsseellff.. Focus on what you can do to make life better for yourself.

Learn about supportive therapies for Pompe disease, and talk with your health-care team about which ones are right for you. Try to get enough rest and exer-cise. Educate yourself about Pompe disease so that you can be an active mem-ber of your healthcare team

■ AAddjjuussttiinngg yyoouurr eexxppeeccttaattiioonnss.. Accept that yourabilities may change from day to day. Set some priorities, and put your energyinto doing the things that are most important to you. Seek professional counseling if you are having trouble coping with the impact of Pompe diseaseon your family relationships, daily life, or personal goals

When you feelready, explore waysto help yourself

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PPllaannnniinngg ffoorr ffiinnaanncciiaall nneeeeddssWhen you are facing the prospect of lifelong medical care, it is important to review your insurance plan to know what type of health insurance coverage youhave. You may need to seek financial aid for medical costs and other expenses notcovered by insurance. Financial assistance is available to help patients with Pompedisease and their families cover certain expenses, but it may take some persistence to find it. To learn more, contact the groups listed onpages 30 to 32.

CChhoooossiinngg tthhee rriigghhtt eeqquuiippmmeenntt ffoorr yyoouurr nneeeeddssAdaptive equipment helps people with Pompe disease stay mobile and enablesthem to be more independent. To choose the right equipment for your needs, besure to get advice from your doctor, occupational or physical therapist, and otherparents or people with Pompe disease. Think about how your needs may changeover time and try out equipment before you buy it. The chart on the next pagelists examples of the types of equipment used by people with Pompe disease.

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CCoommmmuunniiccaattiinngg aanndd bbeeiinngg iinnddeeppeennddeenntt

AAddaappttiivvee ddeevviicceess Cellular telephone, computer, intercom, universal remote, medical alert systems

HHooww tthheeyy hheellpp ■ Help you stay connected to the outside world■ Make you feel safer and more secure in your home■ Help you control electronic equipment in your

home, such as lamps, TV, DVD player

GGeettttiinngg aarroouunndd

AAddaappttiivvee ddeevviicceess Foot splint, folding cane, scooter, wheelchair, adapted car

HHooww tthheeyy hheellpp ■ Provide support if you are still able to walk■ Help you stay active and independent if

you are no longer able to walk

SSiittttiinngg,, ssttaannddiinngg,, rreessttiinngg

AAddaappttiivvee ddeevviicceess Cushion, seating shell, stand-up chair, hospital bed, foam mattress

HHooww tthheeyy hheellpp ■ Increase comfort by taking pressure off weak muscles

■ Make it easier to get up from a chair or bed

TTooiilleettiinngg aanndd sseellff--ccaarree

AAddaappttiivvee ddeevviicceess Grab bars, pedestal sink, handheld shower or adjustable-height shower heads, roll-in shower, bath bench, showerchair, lifter, raised toilet seat, adapted toilet

HHooww tthheeyy hheellpp ■ Help you get to all areas of the bathroom■ Improve safety■ Afford privacy and independence

The right equipment can promote independence

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MMuussccuullaarr DDyyssttrroopphhyy CCaammppaaiiggnn ((MMDDCC))Based in the United Kingdom, MDC offers practical, medical, and emotional support to people with neuromuscular conditions and their families and online fact sheets on specific conditions. Provides referrals to MDC Care Advisors at clinics in the UK.

020-7720-8055 (UK)www.muscular-dystrophy.org

NNaattiioonnaall OOrrggaanniizzaattiioonn ffoorr RRaarree DDiissoorrddeerrss,, IInncc.. ((NNOORRDD))Maintains a database of information on more than 1100 rare diseases.Distributes a free booklet for physicians about Pompe disease.

1-800-999-6673 or 1-203-744-0100 (USA)www.rarediseases.org

TThhee PPoommppee’’ss GGrroouupp ooff tthhee AAssssoocciiaattiioonn ffoorr GGllyyccooggeenn SSttoorraaggee DDiisseeaassee ((UUKK))Sponsors an online support community for people affected byPompe disease. Shares success stories, concerns, and updates on researchadvances through its Web site, newsletter, and guide for families.

017-3023-1554 (UK) www.pompe.org.uk

UUnniitteedd PPoommppee FFoouunnddaattiioonnAssists patients with Pompe disease and their families with medical costs and other expenses that may not be covered by insurance.

1-559-227-1898 (USA)www.unitedpompe.com

Where can I find more information and support?*Though Pompe disease is rare, there are patient groups and organizations through-out the world that offer information, advice, and support to people living withPompe disease.

AAcciidd MMaallttaassee DDeeffiicciieennccyy AAssssoocciiaattiioonn ((AAMMDDAA))Promotes awareness of Pompe disease through teleconferences, newsletters, andreferrals to patients and families.

1-210-494-6144 (USA)www.amda-pompe.org

IInntteerrnnaattiioonnaall PPoommppee AAssssoocciiaattiioonn ((IIPPAA))A federation of Pompe disease patient groups worldwide, the IPA provides referralsto group contacts, organizes international conferences, and through its Web site,reports the latest news on clinical trials, treatment studies, and standards of carefor Pompe disease.

31-35-548-0461 (The Netherlands)www.worldpompe.org

MMuussccuullaarr DDyyssttrroopphhyy AAssssoocciiaattiioonn ((MMDDAA))Based in the United States, MDA provides comprehensive medical services to indi-viduals affected by neuromuscular diseases, including Pompe disease. The Website has a directory of MDA clinics at hospitals throughout the United States.

1-800-572-1717 (USA)www.mdausa.org

*The Web sites referenced in this booklet are maintained by third parties over whom Genzyme Corporation has no control. As such, Genzyme Corporation makes no representation as to the accuracy or any other aspect of the information contained on such Web sites.

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Resources available from Genzyme As a partner in the effort to manage the challenges of living with Pompe disease,Genzyme offers a wide range of support services to people with Pompe disease and their families.

GGeennzzyymmee TTrreeaattmmeenntt SSuuppppoorrtt A team of nurses and other healthcare professionals are available to provide confi-dential, one-on-one insurance counseling to patients and families who have aUnited States health insurance policy.

MMeeddiiccaall IInnffoorrmmaattiioonnThe Medical Information group can answer questions about Pompe disease andprovide you with information.

PPaattiieenntt AAddvvooccaaccyyThis confidential service offers support to patients and families, such as finding resources or healthcare providers in their community.

For the services described above, use the following contact information:

Call toll free 1-800-745-4447 or 1-617-768-9000.

Monday–Friday 8:00 AM to 6:00 PM, US eastern time

Where do I go from here?

When you're dealing with a disease that spans

the spectrum from mild muscle weakness to

severe disability, there will always be uncertain-

ty about what the future may hold. And every-

one affected by Pompe disease must find a way

to cope with daily struggles and lifelong chal-

lenges.

Learning about Pompe disease, taking time

for yourself, tapping into support resources,

and reaching out to others for advice, comfort,

wisdom, and understanding can help make

your journey easier as you move from

diagnosis to action.

Pompe Community Visit this online resource to download copies of this booklet, learnmore about Genzyme’s services, and find links to otherresources.

www.pompe.com

Pompe RegistryThe Pompe Registry, sponsored and administered by Genzyme, is adatabase of medical information on patients with Pompe disease. Thecollective information from the reg-istry is used to increase the under-standing of the disease and to monitor patient outcomes.

www.pomperegistry.com