Metabolic Diseases of Muscle

Home , Metabolic disorder, Muscle weakness

Facts About Metabolic Diseases of Muscle

Updated December 2009 Dear Friends:

f you’ve just learned that you or a loved my beautiful wife and three children. I Ione has a metabolic muscle disorder, work full time as a human resource pro- you’re probably both relieved and con- fessional, attend college, and spend my cerned. That’s how I felt when I learned at spare time remodeling houses, camping age 27 that I had muscle phosphorylase and doing the activities I enjoy. deficiency, or McArdle disease. Those whose metabolic disease is more It was a great relief to have a name and disabling will find much support today. an explanation for a problem I’d had since Federal laws guarantee your right to a early childhood. Knowing that my disease public education, equal employment is rare and hard to diagnose helped me opportunity and access to public places. understand why I’d spent so many years Technology makes it possible for many believing I needed to “try harder,” but only people to perform work that’s suited to feeling weaker when I did. It was a relief their levels of ability and health. to know that I wasn’t “lazy” and wasn’t the Part of maintaining a healthy lifestyle is only one with this problem. learning about your metabolic muscle But getting a diagnosis also raised some disease. I take care of myself by avoid- questions. ing injury, eating healthy and visiting the doctor regularly. Meeting other people What treatment was there? Would my with McArdle disease, participating in symptoms get worse? Did the disease medical research and talking to doctors affect more than my voluntary muscles? have helped me take control of my life. How could I avoid episodes of weakness? Learning more about your disease is just Would my children have the same dis- the beginning of your journey. ease? “MDA is Here to Help You,” on page 13, All those questions are addressed in this Keith Stout describes the many services MDA offers. booklet from the Muscular Dystrophy The Association’s scientists are making Association. MDA offers information and great progress in understanding metabolic support that will help you move from self- diseases and finding treatments for them. doubt to self-management of your meta- We all pray for the day when no one has bolic disorder. to go through the physical and emotional pain that these diseases can cause. You can, to a great extent, manage your disorder and minimize some of the seri- This booklet will give you the basic facts ous effects. I’ve learned how to say no to about your metabolic muscle disease, activities that could do harm. I’ve learned and MDA will help you answer all your to watch for signs of muscle breakdown questions as they arise. As you face the so I can avoid kidney failure. I know what challenges ahead, please remember that treatment I need in case of an emergency. you’re not alone. Metabolic muscle diseases affect each person differently, but for most of us, it doesn’t limit our lives as much as you Keith Stout may fear. Edmond, Oklahoma I’m in my mid-40s and live a very active lifestyle. My life is full and rewarding with

2 Metabolic Diseases of Muscle • ©2009 MDA What are Metabolic Diseases of Muscle? etabolic diseases of muscle were There are 10 metabolic diseases of Mfirst recognized in the second muscle (myopathies) in MDA’s pro- half of the 20th century. Each of these gram. Each one gets its name from disorders is caused by a different the substance that’s lacking: genetic defect that impairs the body’s metabolism, the collection of chemical • acid maltase deficiency changes that occur within cells during (Pompe disease) normal functioning. • carnitine deficiency Specifically, the metabolic diseases of heart • carnitine palmityl transferase muscle interfere with chemical reac- deficiency voluntary tions involved in drawing energy from muscles food. Normally, fuel molecules derived • debrancher enzyme deficiency from food must be broken down fur- (Cori or Forbes disease) ther inside each cell before they can be used by the cells’ mitochondria to • lactate dehydrogenase deficiency make the energy molecule ATP. • myoadenylate deaminase liver The mitochondria inside each cell deficiency could be called the cell’s “engines.” • phosphofructokinase deficiency The metabolic muscle diseases are (Tarui disease) caused by problems in the way certain fuel molecules are processed before • phosphoglycerate kinase deficiency they enter the mitochondria, or by the inability to get fuel molecules into • phosphoglycerate mutase mitochondria. deficiency kidneys Muscles require a lot of energy in the • phosphorylase deficiency form of ATP to work properly. When (McArdle disease) energy levels become too low, muscle weakness and exercise intolerance What causes with muscle pain or cramps may metabolic diseases? occur. Nine of the diseases in this brochure are In a few metabolic muscle disorders, caused by defects in the enzymes that symptoms aren’t caused so much by control chemical reactions used to break a lack of energy, but rather by unused down food. Enzyme defects are caused fuel molecules that build up inside by flaws in the genes that govern pro- muscle cells. This buildup may damage duction of the enzymes. the cells, leading to chronic weakness. The 10th disease, carnitine deficiency, Metabolic diseases of muscle can affect all the body’s voluntary muscles, such as those in the Metabolic muscle diseases that have is caused by lack of a small, natu- arms, legs and trunk. Some also can involve their onset in infancy tend to be the rally occurring molecule that’s not an increased risk of heart or liver diseases, and the enzyme but is involved in metabolism. effects can damage the kidneys. most severe, and some forms are fatal. Those that begin in childhood or Enzymes are special types of proteins adulthood tend to be less severe, and that act like little machines on a micro- changes in diet and lifestyle can help scopic assembly line, each performing most people with the milder forms a different function to break down food adjust. molecules into fuel. When one of the

3 Metabolic Diseases of Muscle • ©2009 MDA enzymes in the line is defective, the process weakness in a person who has the disease goes more slowly or shuts down entirely. because of a genetic flaw. Our bodies can use carbohydrates (starches What happens to someone and sugars), fats and protein for fuel. Defects in the cells’ carbohydrate- and fat- with a metabolic disease? processing pathways usually lead to weak- Exercise intolerance ness in the voluntary muscles, but also may The main symptom of most of the meta- affect the heart, kidneys or liver. Although bolic myopathies is difficulty performing defects in protein-processing pathways can some types of exercise, a situation known occur as well, these usually lead to different as exercise intolerance, in which the per- kinds of disorders that affect other organs. son becomes tired very easily.

A gene is a “recipe” or set of instructions The degree of exercise intolerance in the for making a protein, such as an enzyme. A metabolic myopathies varies greatly between defect in the gene may cause the protein to disorders and even from one individual to be made incorrectly or not at all, leading to the next within a disorder. For instance, a deficiency in the amount of that enzyme. some people may run into trouble only when Genes are passed from parents to children. jogging, while others may have trouble after Therefore, gene defects can be inherited. mild exertion such as walking across a park- (See “Does it Run in the Family?” on page The main symptom of ing lot or even blow-drying their hair. Each 11.) most of the metabolic person must learn his activity limitations. myopathies is difficulty The metabolic muscle diseases aren’t In general, people with defects in their performing some kind of contagious, and they aren’t caused by cer- carbohydrate-processing pathways tend exercise. tain kinds of exercise or lack of exercise. to become very tired at the beginning of However, exercise or fasting (not eating exercise but may experience a renewed regularly) may bring on episodes of muscle feeling of energy after 10 or 15 minutes.

FUEL

In normal metabolism, food provides fuel that’s processed inside the cells, pro- ducing energy (ATP) for muscle contraction and other cellular functions. In metabolic myopathies, missing enzymes prevent mitochondria from properly processing fuel, and no energy is produced for muscle function.

4 Metabolic Diseases of Muscle • ©2009 MDA On the other hand, those with carnitine progressive muscle weakness, rather than palmityl transferase deficiency (CPT) may exercise intolerance, is the primary symp- experience fatigue only after prolonged tom. Over time, people with acid maltase exercise. deficiency or debrancher enzyme deficiency may eventually need a wheelchair A person with exercise intolerance also to get around and, as respiratory muscles may experience painful muscle cramps weaken, may require ventilatory assistance and/or injury-induced pain during or after to provide extra oxygen at night. All three exercising. of these disorders may be associated with The exercise-induced cramps (actually sharp heart problems. contractions that may seem to temporar- It’s important to realize that, although the ily “lock” the muscles) are especially noted metabolic muscle diseases characterized in many of the disorders of carbohydrate by exercise intolerance typically don’t metabolism and, rarely, in myoadenylate involve muscle weakness, some chronic deaminase deficiency. The injury-induced or permanent weakness can develop in pain is caused by acute muscle breakdown, response to repeated episodes of rhab- a process called rhabdomyolysis, which domyolysis and to the normal loss of may occur in any metabolic muscle disorder strength that occurs with aging. The and is particularly noted in CPT. degree of muscle weakness that devel- A person with exercise Episodes of rhabdomyolysis usually occur ops in these disorders is extremely vari- intolerance also may when a person with a metabolic myopathy able and may depend on such factors as experience painful muscle “overdoes it” (sometimes unknowingly). genetic background and the number of cramps and/or pain during These episodes, often described as “severe episodes of rhabdomyolysis experienced. or after exercise. muscle pain,” may occur during exercise The diseases involving exercise intoler- or several hours afterward. In those with ance don’t usually progress to the degree carbohydrate-processing disorders, rhab- that a wheelchair or any other mechanical domyolysis may be triggered by aerobic assistance is needed. exercise (such as running or jumping) or isometric exercise (like pushing or pulling Special issues in heavy objects, squatting or standing on tip- metabolic disorders toes). In people with CPT, rhabdomyolysis is • Myoglobinuria: Myoglobinuria refers usually brought on by prolonged, moderate to rust-colored urine caused by the pres- exercise, especially if an affected person ence of myoglobin (a muscle protein). exercises without eating. In CPT, rhabdomy- When overexertion triggers acute muscle olysis may also be triggered by illness, cold, breakdown (rhabdomyolysis), muscle pro- fasting, stress or menstruation. teins like creatine kinase and myoglobin Because rhabdomyolysis is painful and are released into the blood and ultimately can cause extensive kidney damage, many appear in the urine. Myoglobinuria can people with metabolic muscle diseases try cause severe kidney damage if untreated. to avoid triggering these episodes by modi- Incidences of myoglobinuria should be fying their physical activities or diet. Your dealt with as emergencies and may require MDA clinic director can help you work out intravenous fluids to avoid renal failure. a lifestyle plan to optimize your health and • Emergencies: The metabolic muscle abilities. diseases are so rare that emergency room Muscle weakness staffs are frequently unfamiliar with them. In acid maltase deficiency, carnitine defi- As a result, they may not treat episodes ciency and debrancher enzyme deficiency, properly (with fluids and pain medica-

5 Metabolic Diseases of Muscle • ©2009 MDA tions) or may give the patient food or How are metabolic anesthesia that could trigger further prob- diseases of muscle treated? lems. In April 2006, the U.S. Food and Drug People with these disorders may want to Administration (FDA) approved Myozyme, consider carrying a treatment “protocol” a synthetic form of the acid maltase listing their doctor’s phone number, the enzyme, manufactured by Genzyme of patient’s current medications and dietary Cambridge, Mass., for the treatment of requirements, and guidelines for handling Pompe disease. emergency situations. A MedicAlert bracelet also can be worn. The enzyme replacement therapy requires intravenous infusions of the drug, and • Anesthesia: People with metabolic has significantly improved survival in muscle disorders may be at higher risk for patients with infantile-onset Pompe dis- a potentially fatal reaction to certain com- ease. A December 2007 trial of Myozyme mon general anesthetics (typically combi- in patients who were at least 8 years old nations of halothane and succinylcholine). showed it improved walking endurance This reaction, called malignant hyperther- and respiratory function in that group as mia, can be avoided in planned surgeries well. by using lower-risk anesthetics. However, it’s a good idea to wear a MedicAlert For many other people with metabolic For many with metabolic bracelet stating this susceptibility in case muscle diseases, the only treatment need- muscle diseases, the only of an emergency. ed is to understand what activities and treatment needed is to situations tend to trigger attacks of rhab- understand what activities • Cardiac care: People with debrancher domyolysis. A small percentage of adults and situations tend to trigger enzyme deficiency, carnitine deficiency with metabolic disorders may experience attacks. and acid maltase deficiency may develop painful muscle cramps that have no obvi- significant heart problems. In the case ous triggers; painkillers and meditation of primary carnitine deficiency, the only techniques may be effective under these symptom may be heart failure; however, circumstances. this disorder responds well to carnitine supplementation. If you’re at risk for car- In addition, some people with metabolic diac problems, a cardiologist who’s famil- disorders have benefited from dietary iar with your disorder should monitor your changes. There’s evidence that those with heart function. carbohydrate-processing problems may be helped by a high-protein diet, while those • Respiratory care: Acid maltase defi- with difficulty processing fats may do well ciency and debrancher enzyme deficiency on a diet high in carbohydrates and low tend to weaken the respiratory muscles, in fat. Carnitine supplements are usually those that operate the lungs, meaning given for carnitine deficiency and can be that a person with one of these disorders very effective in reversing heart failure in may require supplemental oxygen at some this disorder. point. If you’re at risk for respiratory problems, your breathing should be moni- Please consult your doctor before under- tored regularly by a specialist. Also, be taking any special diets. Your MDA clinic conscious of symptoms such as unusual director can help you design a specific shortness of breath on exertion or morn- plan suited for your metabolic disorder ing headaches that may indicate that your and your individual needs. breathing is compromised. There’s also emerging evidence that people with some carbohydrate-processing

6 Metabolic Diseases of Muscle • ©2009 MDA disorders, such as McArdle disease, may Electromyography (EMG) uses small benefit from light exercise. Researchers needle electrodes to measure the electri- believe that people who are physically cal currents in a muscle as it contracts. fit are better able to use alternative fuel While an EMG can’t definitively diagnose sources to make energy. Because over- metabolic disease, it can be used to rule exertion can trigger muscle breakdown, out a number of other types of neuromus- you should only undertake an exercise cular disease that cause similar patterns of program under the supervision of a doctor weakness. who’s familiar with your disorder. A muscle biopsy requires the removal It’s unclear whether regular exercise is of a small piece of muscle tissue for beneficial in the fat-metabolizing disor- microscopic analysis. The procedure is ders, such as carnitine palmityl transfer- done either surgically, with an incision ase deficiency. to expose the target muscle, or with a needle. A skin biopsy also is sometimes Because of their rarity, the characteristics performed. of several of these diseases aren’t well known. Other tests that may be needed include an electrocardiogram to test heart function, How are metabolic diseases and brain imaging studies such as CT or MRI scans. It’s important to get an of muscle diagnosed? accurate diagnosis of a It’s important to get an accurate diagno- Genetic tests, using a blood sample, can specific metabolic myopathy sis of a specific metabolic myopathy so analyze the person’s genes for particular so diet and exercise can the affected person can modify diet and defects that cause metabolic disease, but be modified and symptoms exercise and monitor potentially serious these tests often aren’t necessary for diag- monitored. disease effects. Because these diseases nosis or for determining treatment. are rare, many people with metabolic disorders of muscle have spent some What are the symptoms time trying to find out what caused their and characteristics of each muscle weakness, myoglobinuria or other type of disease? symptoms. The diagnostic process usually begins with a careful medical history, a CARBOHYDRATE-PROCESSING physical exam and a neurological exam to DISORDERS test reflexes, strength and the distribution These disorders affect the breakdown of of weakness. glycogen or glucose (complex and simple carbohydrates) and also are called glyco- Several specialized tests are used to con- genosis disorders. firm a suspected diagnosis of metabolic disease: Acid maltase deficiency Also called: Blood tests can be used to detect the Glycogenosis type 2, acid-alpha gluco- presence of certain chemicals in the blood sidase deficiency, Pompe disease, lyso- that may indicate some metabolic dis- somal storage disease eases. Onset: An exercise test is used to monitor a per- Infancy to adulthood son’s response to intense or moderate exercise. Blood samples are taken during Inheritance: exercise for testing. Autosomal recessive

7 Metabolic Diseases of Muscle • ©2009 MDA Symptoms: often improve around puberty. Muscle Causes slowly progressive weakness, weakness may develop later in life, and especially of the respiratory muscles and is most pronounced in the muscles of those of the hips, upper legs, shoulders the forearms, hands, lower legs and feet. and upper arms. Enlargement of the Weakness often is accompanied by loss of tongue and liver impairment occur in muscle bulk. The heart can be affected as the infantile form, but rarely in the older well, and heart function should be moni- forms. Cardiac involvement may occur tored closely. in the infantile or childhood forms, but is less common in adults. The childhood Phosphorylase deficiency and adult-onset forms are less severe Also called: than the infantile form, but may cause Myophosphorylase deficiency, McArdle severe weakness and respiratory insuf- disease, glycogenosis type 5 ficiency, and, without treatment, shortened Onset: life span. Untreated, the infantile form of Childhood to adulthood Pompe disease often leads to death within the first year of life. Inheritance: Autosomal recessive Until recently, there was no treatment of this condition and the only remedy was Symptoms: In April 2006, the U.S. Food supportive medical care. In April 2006, the Causes exercise intolerance, cramps, mus- and Drug Administration U.S. Food and Drug Administration grant- cle pain and weakness shortly after the granted approval for the use ed approval for the use of Myozyme as a beginning of exercise. A person with this of Myozyme as a treatment treatment for Pompe disease. The drug disorder may tolerate light-to-moderate for Pompe disease. was developed by Genzyme Corporation exercise such as walking on level ground, of Cambridge, Mass., with support from but strenuous exercise will usually bring MDA. It substitutes for the enzyme miss- on symptoms quickly. Resting may lead ing in Pompe disease and may keep to a “second wind,” in which activity is muscle cells from dying. then better tolerated. Isometric exercises that require strength, such as lifting heavy Your MDA clinic director will keep you objects, squatting or standing on tiptoe, abreast of ongoing clinical trials for the also may cause muscle damage. disease and work with you to make the best decisions for care. The symptoms of McArdle disease vary in severity among people and even within the Debrancher enzyme deficiency same person from day to day. Symptoms Also called: usually don’t persist between attacks, Cori or Forbes disease, glycogenosis although fixed weakness later in life is type 3 possible. Onset: Phosphofructokinase deficiency Childhood to adulthood Also called: Inheritance: Glycogenosis type 7, Tarui disease Autosomal recessive Onset: Symptoms: Childhood to adulthood Principally affects the liver, causing Inheritance: swelling of the liver, slowing of growth, Autosomal recessive low blood sugar levels and, sometimes, seizures. In children, these symptoms

8 Metabolic Diseases of Muscle • ©2009 MDA Symptoms: Lactate dehydrogenase deficiency Causes exercise intolerance, with pain, Also called: cramps and, occasionally, myoglobinuria. Glycogenosis type 11 Symptoms are very similar to those of phosphorylase deficiency, but people with Onset: this disorder are less likely to experience Early adulthood the “second wind” phenomenon. Inheritance: A carbohydrate meal typically worsens Autosomal recessive exercise capacity in this condition by Symptoms: lowering blood levels of fats, which are Causes exercise intolerance and episodes the major muscle energy fuels for those of myoglobinuria. A skin rash is common, with the disorder. A partial deficiency of probably because skin cells need lactate phosphofructokinase in the red blood cells dehydrogenase. results in the breakdown of those cells and an increase in blood levels of bilirubin, FAT-PROCESSING DISORDERS though the person usually experiences no Carnitine deficiency symptoms. Onset: Phosphoglycerate kinase deficiency Childhood Also called: A carbohydrate meal Inheritance: Glycogenosis type 9 typically worsens Autosomal recessive exercise capacity in Onset: Symptoms: phosphofructokinase Infancy to early adulthood This slowly progressive disorder causes deficiency by lowering cardiac disease and muscle weakness Inheritance: blood levels of fats. in the hips, shoulders, and upper arms X-linked recessive and legs. The neck and jaw muscles may Symptoms: also be weak. Carnitine deficiency may May cause anemia, enlargement of the occur secondary to other metabolic dis- spleen, mental retardation and epilepsy. eases (secondary carnitine deficiency) or More rarely, weakness, exercise intoler- in response to a genetic mutation (gene ance, muscle cramps and episodes of defect) in the protein responsible for myoglobinuria also occur. bringing carnitine into the cell (primary carnitine deficiency). Phosphoglycerate mutase deficiency Primary carnitine deficiency can often be Also called: treated successfully with carnitine supple- Glycogenosis type 10 ments.

Onset: Carnitine palmityl transferase Childhood to early adulthood deficiency Onset: Inheritance: Childhood to early adulthood Autosomal recessive Inheritance: Symptoms: Autosomal recessive Causes exercise intolerance, cramps, muscle pain and, sometimes, myoglobinuria. Symptoms: Permanent weakness is rare. Symptoms usually are brought on by prolonged and intense exercise, especially

9 Metabolic Diseases of Muscle • ©2009 MDA in combination with fasting, but may not DISORDER AFFECTING ATP appear for several hours after activity RECYCLING stops. Short periods of exercise usually Myoadenylate deaminase don’t provoke symptoms. Symptoms deficiency also can be brought on by illness, cold, Onset: stress or menstruation. This disorder Adulthood causes muscle pain, stiffness and tender- ness, while weakness is less common. Inheritance: Breakdown of muscle tissue during an Autosomal recessive attack can cause myoglobinuria. Symptoms: Interferes with the recycling of the major energy molecule of the cell (called ATP). It may cause exercise intolerance, cramps and muscle pain, although, in many cases, people with deficiencies in this enzyme may experience no symptoms.

Fueling the Muscles

Roadblocks Lead to Disorders

Skeletal muscles normally depend on energy from carbohydrates and fats. These fuels can be stored in the muscle (glycogen) or imported directly from the bloodstream (glucose and fatty acids). When a genetic defect ( ) interferes with the processing of specific fuels, energy shortages can occur and toxic byproducts may build up. Some people may be able to bypass their defects by adjusting diet or exercise to draw energy more efficiently from unaffected pathways.

10 Metabolic Diseases of Muscle • ©2009 MDA Does it Run in the Family? n being told they have a genetic dis- A good way to find out more about O order such as a metabolic muscle dis- these risks is to talk to your MDA clinic ease, bewildered patients often ask, “But it physician or ask to see the genetic doesn’t run in the family, so how could it counselor at the MDA clinic. Also, see be genetic?” MDA’s booklet, “Facts About Genetics and Neuromuscular Diseases.” Metabolic myopathies can run in a family, even if only one person in the biological family has it. This is because of the ways in which genetic diseases are inherited.

Most of the metabolic diseases of muscle are inherited in an autosomal recessive pattern, meaning that a person needs two defective genes in order to have the disease. One copy is inherited from each parent, neither of whom would normally have symptoms.

Many parents have no idea Thus, the disease appears to have they’re carriers of a disease occurred “out of the blue,” but in real- until they have a child who ity, both parents may be carriers, silently has the disease. harboring the genetic mutation (a flaw in the gene). Many parents have no idea they’re carriers of a disease until they have a child who has the disease.

Other metabolic disorders have X-linked or autosomal dominant patterns of inheritance, each of which carries different risks for transmission to children. In some cases, a single disorder is associated with more than one pattern of inheritance.

Finally, metabolic disorders actually can occur “out of the blue” when a new mutation appears with a baby’s concep- tion. These are called spontaneous muta- tions, and, after they occur, they can be passed on to the next generation.

The risk of passing on a metabolic myopathy to your children depends on many circumstances, including exactly which type of metabolic disease has been diagnosed.

11 Metabolic Diseases of Muscle • ©2009 MDA MDA’s Search for Treatments and Cures he MDA Web site is constantly updated MDA, for the treatment of Pompe disease. Twith the latest information about the Since Myozyme became available, the neuromuscular diseases in its program. outlook for people of all ages with Pompe See the latest research news at www.mda. disease is considerably brighter, though org/whatsnew. improvement of the drug continues to be the focus of ongoing research. MDA-funded scientists are pursuing a number of promising leads in their quest Targets now being pursued in research to understand the causes of the metabolic include: better diagnosis of metabolic diseases of muscle. diseases, to allow better identification of at-risk individuals and earlier treatment; To date, scientists have isolated all of the continued examination of the role of exer- genes involved in the metabolic myopa- cise and diet in metabolic diseases; devel- thies described in this booklet, and their opment of animal models of metabolic genetic codes have been unraveled, diseases, both to improve understanding offering insight into how particular gene of the diseases and to test possible treat- defects lead to disease. In addition, isola- ments; development of enzyme replace- tion of genes has allowed researchers to ment therapies in addition to Myozyme for begin experiments with gene therapy, a enzyme deficiencies; and development of potential cure for some metabolic dis- gene therapies for metabolic diseases. eases.

The knowledge MDA-funded researchers are obtaining about the mechanisms by which metabolic gene defects cause disease may lead to other strategies for pre- vention and treatment. MDA’s extensive research program includes studies to help in developing new treatments for metabolic diseases of muscle, such as strategies designed to replace the enzymes that are missing in these disorders.

Efforts to develop such “enzyme replacement therapies” already have been rewarded with the U.S. Food and Drug Administration’s approval in 2006 of Myozyme, a laboratory-modified acid maltase enzyme developed by Genzyme of Cambridge, Mass., with the support of

he Muscular Dystrophy Association Everyone registered with MDA automati- Toffers a vast array of services to help cally receives Quest, MDA’s award-win- you and your family deal with metabolic ning quarterly magazine. Quest publishes diseases of muscle. The staff at your local detailed articles about research findings, MDA office is there to assist you in many medical and day-to-day care, helpful ways. The Association’s services include: products and devices, social and family issues, and much more. Other MDA pub- • nationwide network of clinics staffed by lications can be found at www.mda.org/ top neuromuscular disease specialists publications; many booklets are available • MDA summer camps for kids with neu- in Spanish. Ask your local office for “MDA romuscular diseases Services for the Individual, Family and Community” and for help with obtaining • help with obtaining durable medical copies of other publications. equipment through its national equipment loan program If you have any questions about metabolic diseases of muscle, someone at MDA will • financial assistance with repairs to all help you find the answer. To reach your types of durable medical equipment local MDA office, call (800) 572-1717.

• annual occupational, physical, respiratory and speech therapy consultations

• annual flu shots

• support groups for those affected, On the cover: spouses, parents or other caregivers Lateef Murdock, who has Pompe disease, composes and produces music in his home • online support services through the studio. He moved from Michigan to Cathedral City, Calif., in 2007 to pursue his music e-community myMDA and through career. He credits MDA “for being there for myMuscleTeam, a program that helps me. I knew I could come out here and still recruit and coordinate in-home help get the great care and treatment I received in Michigan.” MDA’s public health education program helps you stay abreast of research news, medical findings and disability information through magazines, publications, edu- cational speakers, seminars, videos and newsletters.

MDA’s Web site at www.mda.org contains thousands of pages of valuable information, including disease specifics, research findings, clinical trials and past magazine articles.

13 Metabolic Diseases of Muscle • ©2009 MDA MDA’s Purpose and Programs he Muscular Dystrophy Association Metabolic Diseases of Muscle Tfights neuromuscular diseases through Phosphorylase deficiency (McArdle disease) an unparalleled worldwide research effort. Acid maltase deficiency (Pompe disease) The following diseases are included in Phosphofructokinase deficiency MDA’s program: (Tarui disease) Debrancher enzyme deficiency Muscular Dystrophies (Cori or Forbes disease) Myotonic dystrophy (Steinert disease) Mitochondrial myopathy Duchenne muscular dystrophy Carnitine deficiency Becker muscular dystrophy Carnitine palmityl transferase deficiency Limb-girdle muscular dystrophy Phosphoglycerate kinase deficiency Facioscapulohumeral muscular dystrophy Phosphoglycerate mutase deficiency Congenital muscular dystrophy Lactate dehydrogenase deficiency Oculopharyngeal muscular dystrophy Myoadenylate deaminase deficiency Distal muscular dystrophy Emery-Dreifuss muscular dystrophy Myopathies Due to Endocrine Abnormalities Motor Neuron Diseases Hyperthyroid myopathy Amyotrophic lateral sclerosis (ALS) Hypothyroid myopathy Infantile progressive spinal muscular atrophy Other Myopathies (Type 1, Werdnig-Hoffmann disease) Myotonia congenita Intermediate spinal muscular atrophy Paramyotonia congenita (Type 2) Central core disease Juvenile spinal muscular atrophy Nemaline myopathy (Type 3, Kugelberg-Welander disease) Myotubular myopathy Adult spinal muscular atrophy (Type 4) Periodic paralysis Spinal-bulbar muscular atrophy (Kennedy disease) Inflammatory Myopathies Polymyositis Dermatomyositis Inclusion-body myositis Diseases of Neuromuscular Junction Myasthenia gravis MDA’s Web site is constantly Lambert-Eaton (myasthenic) syndrome updated with the latest information Congenital myasthenic syndromes about the diseases in its program. Diseases of Peripheral Nerve Go to www.mda.org. Charcot-Marie-Tooth disease Friedreich’s ataxia Jerry Lewis, National Chairman Dejerine-Sottas disease www.mda.org • (800) 572-1717