Facts About Mitochondrial Myopathies Updated December 2009 Dear Friends: f you are reading this booklet, it’s probably symptoms are common in the general popula- Ibecause you’ve just received a very bewil- tion, such as heart problems, seizures and dering diagnosis: mitochondrial myopathy. diabetes. Therefore, good medical treatments What is a mitochondrial myopathy, and what already exist to help manage many symp- does the term mean? These are questions toms. my wife, Jennifer, and I struggled with when Always remember that researchers are con- our son, Michael, got his diagnosis in 1993. tinually moving toward better treatments, and Mitochondrial myopathies have many dif- ultimately, cures for mitochondrial diseases. ferent faces. As you will read in this booklet, In addition, people with disabilities have great- dozens of varieties of mitochondrial diseases er opportunities than ever before to make the have been identified, with a complex array of most of their abilities, as well as legal rights symptoms. Some symptoms can be so mild to equal employment opportunity and access that they’re hardly noticeable, while others are to public places. Children with physical and life-threatening. cognitive disabilities are guaranteed by law a public education with whatever supports they Michael’s disease causes muscle weakness, need. muscle cramping, fatigue, lack of endurance and poor balance. You or your family member MDA has been a very valuable ally as we con- may have similar symptoms, yet each case is tinue to learn to live with mitochondrial dis- unique. ease. “MDA Is Here to Help You,” on page 14, will tell you more about MDA’s many services. When we first learned that Michael had a mitochondrial myopathy, we naturally were To us, Michael is not a victim of a disease or very frightened and uncertain about the future. a syndrome, but a happy, loving, young man The Kelly family at the MDA Labor Day Telethon. As time passed, we learned that we can do of whom we’re very proud. We’ve discovered things we didn’t think would be possible — that no one can predict exactly how Michael’s we can adapt to the uncertainty, control the or Jennifer’s cases will progress. We’ve been fear, cope with changes as they occur and still blessed to see Michael lead a normal life, have a “normal,” happy family life. earning his Boy Scout Eagle Award and being inducted into the National Honor Society. In 2004 our lives were again turned upside Michael has shown that having a mitochondri- down, when my wife, Jennifer, learned she al disease doesn’t necessarily keep you from too had a mitochondrial disease. Jennifer’s accomplishing anything you set your mind to. symptoms are more severe than Michael’s; she experiences severe muscle weakness, As we struggle to adapt to the changes in our fatigue, gastrointestinal problems, respiratory lives since Jennifer’s diagnosis, it’s reassuring problems and difficulty swallowing. to know that MDA is there for us, assisting us with equipment, clinics, continuing research, This booklet has been prepared to help you and just a friendly voice that understands understand the causes of and treatments for what we are going through. mitochondrial myopathies. We have found information to be a vital tool in managing As you face the challenges ahead, we wish Michael’s and Jennifer’s diseases and achiev- you the same blessing and the comfort of ing the best possible outcome. knowing that you are not alone. From this booklet you’ll also learn a few Richard Kelly encouraging things. For example, although Mansfield, Massachusetts these are very rare disorders, many of their 2 Mitochondrial Myopathies • ©2011 MDA What Are Mitochondrial Diseases? ust as some diseases are named for the Because muscle cells and nerve cells have Jpart of the body they affect (like heart dis- especially high energy needs, muscular and ease), mitochondrial diseases are so-named neurological problems — such as muscle because they affect a specific part of the cells weakness, exercise intolerance, hearing loss, in the body. Specifically, mitochondrial dis- trouble with balance and coordination, sei- eases affect the mitochondria — tiny energy zures and learning deficits — are common factories found inside almost all our cells. features of mitochondrial disease. Other fre- quent complications include impaired vision, Mitochondria are responsible for producing heart defects, diabetes and stunted growth. most of the energy that’s needed for our Usually, a person with a mitochondrial dis- cells to function. In fact, they provide such ease has two or more of these conditions, an important source of energy that a typi- some of which occur together so regularly cal human cell contains hundreds of them. that they’re grouped into syndromes. A mitochondrial disease can shut down some or all the mitochondria, cutting off this A mitochondrial disease that causes promi- essential energy supply. nent muscular problems is called a mito- chondrial myopathy (myo means muscle, Nearly all our cells rely on mitochondria for and pathos means disease), while a mito- a steady energy supply, so a mitochondrial chondrial disease that causes both promi- disease can be a multisystem disorder affect- nent muscular and neurological problems is ing more than one type of cell, tissue or called a mitochondrial encephalomyopathy organ. The exact symptoms aren’t the same (encephalo refers to the brain). for everyone, because a person with mito- chondrial disease can have a unique mixture Despite their many potential effects, mito- of healthy and defective mitochondria, with a chondrial diseases sometimes cause little unique distribution in the body. disability. Sometimes, a person has enough healthy mitochondria to compensate for the MANY defective ones. Also, because some symp- toms of mitochondrial disease (such as diabetes or heart arrhythmia) are common in the general population, there are effective treatments for those symptoms (such as insulin or anti-arrhythmic drugs). INSIDE A SINGLE MITOCHONDRION Each mitochondrion is an energy factory that “imports” sugars and fats, breaks them down and “exports” energy (ATP). 3 Mitochondrial Myopathies • ©2011 MDA This booklet describes general causes, mitochondria. Within each mitochondrion consequences and management of mito- (singular of mitochondria), these proteins chondrial diseases, with an emphasis on make up part of an assembly line that uses myopathies and encephalomyopathies and a fuel molecules derived from food to manu- close look at the most common syndromes. facture the energy molecule ATP. This highly These include: efficient manufacturing process requires oxygen; outside the mitochondrion, there are • Kearns-Sayre syndrome (KSS) less efficient ways of producing ATP without • Leigh syndrome oxygen. • mitochondrial DNA depletion Proteins at the beginning of the mitochon- syndrome (MDS) drial assembly line act like cargo handlers, importing the fuel molecules — sugars and • mitochondrial encephalomyopathy, fats — into the mitochondrion. Next, other lactic acidosis and strokelike proteins break down the sugars and fats, episodes (MELAS) extracting energy in the form of charged par- ticles called electrons. • myoclonus epilepsy with ragged red fibers (MERRF) Proteins toward the end of the line — orga- nized into five groups called complexes I, • mitochondrial neurogastrointestinal II, III, IV and V — harness the energy from encephalomyopathy (MNGIE) those electrons to make ATP. Complexes I Mitochondrial diseases through IV shuttle the electrons down the aren’t contagious, and • neuropathy, ataxia and line and are therefore called the electron they’re not caused by retinitis pigmentosa (NARP) transport chain, and complex V actually anything a person does. • Pearson syndrome churns out ATP, so it’s also called ATP syn- thase. • progressive external ophthalmoplegia (PEO) A deficiency in one or more of these com- plexes is the typical cause of a mitochondrial What causes mitochondrial disease. (In fact, mitochondrial diseases are diseases? sometimes named for a specific deficiency, such as complex I deficiency.) First, mitochondrial diseases aren’t conta- gious, and they aren’t caused by anything a When a cell is filled with defective mitochon- person does. They’re caused by mutations, dria, it not only becomes deprived of ATP — or changes, in genes — the cells’ blueprints it can accumulate a backlog of unused fuel for making proteins. molecules and oxygen, with potentially disas- trous effects. Genes are responsible for building our bod- ies, and are passed from parents to children, In such cases, excess fuel molecules are along with any mutations or defects they used to make ATP by inefficient means, have. That means that mitochondrial diseas- which can generate potentially harmful es are inheritable, although they often affect byproducts such as lactic acid. (This also members of the same family in different occurs when a cell has an inadequate oxygen ways. (For more information about genetic supply, which can happen to muscle cells mutations and mitochondrial disease, see during strenuous exercise.) The buildup of “Does It Run in the Family?” on page 12.) lactic acid in the blood — called lactic aci- dosis — is associated with muscle fatigue, The genes involved in mitochondrial disease and might actually damage muscle and nerve normally make proteins that work inside the tissue. 4 Mitochondrial Myopathies • ©2011 MDA Meanwhile, unused oxygen in the cell can be useful. Sometimes, people with mitochon- converted into destructive compounds called drial myopathies experience loss of muscle reactive oxygen species, including so-called strength in the arms or legs, and might need free radicals. (These are the targets of so- braces or a wheelchair to get around. called antioxidant drugs and vitamins.) Exercise intolerance, also called exertional ATP derived from mitochondria provides the fatigue, refers to unusual feelings of exhaus- main source of power for muscle cell con- tion brought on by physical exertion. The traction and nerve cell firing. So, muscle cells degree of exercise intolerance varies greatly and nerve cells are especially sensitive to among individuals.