A genetic brain disorder is caused by a variation or a mutation in a gene. A variation is a different form of a gene. A mutation is a change in a gene. Genetic brain disorders affect the development and function of the brain.

Some genetic brain disorders are due to random gene mutations or mutations caused by environmental exposure, such as cigarette smoke. Other disorders are inherited, which means that a mutated gene or group of genes is passed down through a family. They can also be due to a combination of both genetic changes and other outside factors.

Some examples of genetic brain disorders include

• Leukodystrophies
• Phenylketonuria
• Tay-Sachs disease
• Wilson disease

Many people with genetic brain disorders fail to produce enough of certain proteins that influence brain development and function. These brain disorders can cause serious problems that affect the nervous system. Some have treatments to control symptoms. Some are life-threatening.

Metabolism is the process your body uses to make energy from the food you eat. Food is made up of proteins, carbohydrates, and fats. Your digestive system breaks the food parts down into sugars and acids, your body's fuel. Your body can use this fuel right away, or it can store the energy in your body. If you have a metabolic disorder, something goes wrong with this process.

One group of these disorders is amino acid metabolism disorders. They include phenylketonuria (PKU) and maple syrup urine disease. Amino acids are "building blocks" that join together to form proteins. If you have one of these disorders, your body may have trouble breaking down certain amino acids. Or there may be a problem getting the amino acids into your cells. These problems cause a buildup of harmful substances in your body. That can lead to serious, sometimes life-threatening, health problems.

These disorders are usually inherited. A baby who is born with one may not have any symptoms right away. Because the disorders can be so serious, early diagnosis and treatment are critical. Newborn babies get screened for many of them, using blood tests.

Treatments may include special diets, medicines, and supplements. Some babies may also need additional treatments if there are complications.

Metabolism is the process your body uses to make energy from the food you eat. Food is made up of proteins, carbohydrates, and fats. Chemicals in your digestive system (enzymes) break the food parts down into sugars and acids, your body's fuel. Your body can use this fuel right away, or it can store the energy in your body tissues. If you have a metabolic disorder, something goes wrong with this process.

Carbohydrate metabolism disorders are a group of metabolic disorders. Normally your enzymes break carbohydrates down into glucose (a type of sugar). If you have one of these disorders, you may not have enough enzymes to break down the carbohydrates. Or the enzymes may not work properly. This causes a harmful amount of sugar to build up in your body. That can lead to health problems, some of which can be serious. Some of the disorders are fatal.

These disorders are inherited. Newborn babies get screened for many of them, using blood tests. If there is a family history of one of these disorders, parents can get genetic testing to see whether they carry the gene. Other genetic tests can tell whether the fetus has the disorder or carries the gene for the disorder.

Treatments may include special diets, supplements, and medicines. Some babies may also need additional treatments, if there are complications. For some disorders, there is no cure, but treatments may help with symptoms.

When you play the piano or hit a tennis ball you are activating the cerebellum. The cerebellum is the area of the brain that controls coordination and balance. Problems with the cerebellum include

• Cancer
• Genetic disorders
• Ataxias - failure of muscle control in the arms and legs that result in movement disorders
• Degeneration - disorders caused by brain cells decreasing in size or wasting away

Treatment of cerebellar disorders depends on the cause. In some cases, there is no cure but treatment may help with symptoms.

Friedreich's ataxia is an inherited disease that damages your nervous system. The damage affects your spinal cord and the nerves that control muscle movement in your arms and legs. Symptoms usually begin between the ages of 5 and 15. The main symptom is ataxia, which means trouble coordinating movements. Specific symptoms include

• Difficulty walking
• Muscle weakness
• Speech problems
• Involuntary eye movements
• Scoliosis (curving of the spine to one side)
• Heart palpitations, from the heart disease which can happen along with Friedreich's ataxia

People with Friedreich's ataxia usually need a wheelchair 15 to 20 years after symptoms first appear. In severe cases, people become incapacitated. There is no cure. You can treat symptoms with medicines, braces, surgery, and physical therapy.

Degenerative nerve diseases affect many of your body's activities, such as balance, movement, talking, breathing, and heart function. Many of these diseases are genetic. Sometimes the cause is a medical condition such as alcoholism, a tumor, or a stroke. Other causes may include toxins, chemicals, and viruses. Sometimes the cause is not known.

Degenerative nerve diseases include

• Alzheimer's disease
• Amyotrophic lateral sclerosis
• Friedreich's ataxia
• Huntington's disease
• Lewy body disease
• Parkinson's disease
• Spinal muscular atrophy

Degenerative nerve diseases can be serious or life-threatening. It depends on the type. Most of them have no cure. Treatments may help improve symptoms, relieve pain, and increase mobility.

Your brain is the control center of your body. It controls your thoughts, memory, speech, and movement. It regulates the function of many organs. It's part of your nervous system, which also includes your spinal cord and peripheral nerves. The nervous system sends signals between your brain and the rest of the body. Your nerves take in information from your senses and send it to the brain to be processed. Your brain and nerves also communicate to help you move and to control your body's functions.

When the brain is healthy, it works quickly and automatically. But when you have a brain disease, it may affect how well you can function and do your daily activities. Some common brain diseases include:

• Brain tumors, which can press on nerves and affect brain function.
• Degenerative nerve diseases, which can affect many of your body's activities, such as balance, movement, talking, breathing, and heart function. Types include Alzheimer's disease and Parkinson's disease.
• Encephalitis (inflammation in the brain), which can lead to problems such as vision loss, weakness, and paralysis.
• Genetic brain disorders, which are caused by changes in genes (also called variants or mutations). These disorders can affect the development and function of the brain.
• Strokes, which can cause a loss of brain cells and can affect your ability to think clearly.
• Traumatic brain injuries (TBIs), which can affect brain function. They may range from mild to severe. The effects of a TBI may be temporary or permanent.

The symptoms of brain diseases vary widely, depending on the specific problem. In some cases, damage is permanent. In other cases, treatments such as surgery, medicines, or therapies such as physical, occupational, and speech therapies, may cure the disease or improve the symptoms.

Ataxia-telangiectasia (A-T) is a rare, inherited disease. It affects the nervous system, immune system, and other body systems. Symptoms appear in young children, usually before age 5. They include

• Ataxia - trouble coordinating movements
• Poor balance
• Slurred speech
• Tiny, red spider veins, called telangiectasias, on the skin and eyes
• Lung infections
• Delayed physical and sexual development

People with A-T have an increased risk of developing diabetes and cancers, especially lymphoma and leukemia. Although it affects the brain, people with A-T usually have normal or high intelligence.

A-T has no cure. Treatments might improve some symptoms. They include injections to strengthen the immune system, physical and speech therapy, and high-dose vitamins.

Genes are the building blocks of heredity. They are passed from parent to child. They hold DNA, the instructions for making proteins. Proteins do most of the work in cells. They move molecules from one place to another, build structures, break down toxins, and do many other maintenance jobs.

Sometimes there is a mutation, a change in a gene or genes. The mutation changes the gene's instructions for making a protein, so the protein does not work properly or is missing entirely. This can cause a medical condition called a genetic disorder.

You can inherit a gene mutation from one or both parents. A mutation can also happen during your lifetime.

There are three types of genetic disorders:

• Single-gene disorders, where a mutation affects one gene. Sickle cell anemia is an example.
• Chromosomal disorders, where chromosomes (or parts of chromosomes) are missing or changed. Chromosomes are the structures that hold our genes. Down syndrome is a chromosomal disorder.
• Complex disorders, where there are mutations in two or more genes. Often your lifestyle and environment also play a role. Colon cancer is an example.

Genetic tests on blood and other tissue can identify genetic disorders.

A genetic disorder is a disease caused in whole or in part by a change in the DNA sequence away from the normal sequence. Genetic disorders can be caused by a mutation in one gene (monogenic disorder), by mutations in multiple genes (multifactorial inheritance disorder), by a combination of gene mutations and environmental factors, or by damage to chromosomes (changes in the number or structure of entire chromosomes, the structures that carry genes).

As we unlock the secrets of the human genome (the complete set of human genes), we are learning that nearly all diseases have a genetic component. Some diseases are caused by mutations that are inherited from the parents and are present in an individual at birth, like sickle cell disease. Other diseases are caused by acquired mutations in a gene or group of genes that occur during a person's life. Such mutations are not inherited from a parent, but occur either randomly or due to some environmental exposure (such as cigarette smoke). These include many cancers, as well as some forms of neurofibromatosis.

What is genetic testing?

Genetic testing is a type of medical test that looks for changes in your DNA. DNA is short for deoxyribonucleic acid. It contains the genetic instructions in all living things. Genetic tests analyze your cells or tissue to look for any changes in

• Genes, which are parts of DNA that carry the information needed to make a protein
• Chromosomes, which are thread-like structures in your cells. They contain DNA and proteins.
• Proteins, which do most of the work in your cells. Testing can look for changes in the amount and activity level of proteins. If it finds changes, it might be due to changes in your DNA.

Why is genetic testing done?

Genetic testing may be done for many different reasons, including to

• Find genetic diseases in unborn babies. This is one type of prenatal testing.
• Screen newborn babies for certain treatable conditions
• Lower the risk of genetic diseases in embryos that were created using assisted reproductive technology
• Find out if you carry a gene for a certain disease that could be passed on to your children. This is called carrier testing.
• See whether you are at increased risk of developing a specific disease. This may be done for a disease that runs in your family.
• Diagnose certain diseases
• Identify genetic changes that may be causing or contributing to a disease that you were already diagnosed with
• Figure out how severe a disease is
• Help guide your doctor in deciding the best medicine and dosage for you. This is called pharmacogenomic testing.

How is genetic testing done?

Genetic tests are often done on a blood or cheek swab sample. But they may also be done on samples of hair, saliva, skin, amniotic fluid (the fluid that surrounds a fetus during pregnancy), or other tissue. The sample is sent to a laboratory. There, a lab technician will use one of several different techniques to look for genetic changes.

What are the benefits of genetic testing?

The benefits of genetic testing include

• Helping doctors make recommendations for treatment or monitoring
• Giving you more information for making decisions about your health and your family's health:
  • If you find out that you are at risk for a certain disease, you might take steps to lower that risk. For example, you may find out that you should be screened for a disease earlier and more often. Or you might decide to make healthy lifestyle changes.
  • If you find out that you are not at risk for a certain disease, then you can skip unnecessary checkups or screenings
  • A test could give you information that helps you make decisions about having children
• Identifying genetic disorders early in life so treatment can be started as soon as possible

What are the drawbacks of genetic testing?

The physical risks of the different types of genetic testing are small. But there can be emotional, social, or financial drawbacks:

• Depending on the results, you may feel angry, depressed, anxious, or guilty. This can be especially true if you are diagnosed with a disease that does not have effective treatments.
• You may be worried about genetic discrimination in employment or insurance
• Genetic testing may give you limited information about a genetic disease. For example, it cannot tell you whether you will have symptoms, how severe a disease might be, or whether a disease will get worse over time.
• Some genetic tests are expensive, and health insurance might only cover part of the cost. Or they may not cover it at all.

How do I decide whether to be tested?

The decision about whether to have genetic testing is complex. In addition to discussing the test with your health care provider, you can meet with a genetic counselor. Genetic counselors have specialized degrees and experience in genetics and counseling. They can help you understand the tests and weigh the risks and benefits. If you do get a test, they can explain the results and make sure that you have the support that you need.

Genetic testing is a type of medical test that identifies changes in genes, chromosomes, or proteins. The results of a genetic test can confirm or rule out a suspected genetic condition or help determine a person’s chance of developing or passing on a genetic disorder. More than 77,000 genetic tests are currently in use, and others are being developed.

Genetic testing involves looking for changes in:

• Genes: Gene tests study DNA sequences to identify variations (mutations) in genes that can cause or increase the risk of a genetic disorder. Gene tests can be narrow or large in scope, analyzing an individual DNA building block (nucleotide), one or more genes, or all of a person’s DNA (which is known as their genome).
• Chromosomes: Chromosomal genetic tests analyze whole chromosomes or long lengths of DNA to see if there are large genetic changes, such as an extra copy of a chromosome, that cause a genetic condition.
• Proteins: Biochemical genetic tests study the amount or activity level of proteins or enzymes; abnormalities in either can indicate changes to the DNA that result in a genetic disorder.

Genetic testing is voluntary. Because testing has benefitsas well as limitations and risks, the decision about whether to be tested is a personal and complex one. A geneticist or genetic counselor can help by providing information about the pros and cons of the test and discussing the social and emotional aspects of testing.

Genetic testing uses laboratory methods to look at your genes, which are the DNA instructions you inherit from your mother and your father.

How are genetic tests used?

Genetic tests may be used to identify increased risks of health problems, to choose treatments, or to assess responses to treatments.

What can I learn?

There are many different types of genetic tests. Genetic tests can help to:

• Diagnose disease

• Identify gene changes that are responsible for an already diagnosed disease

• Determine the severity of a disease

• Guide doctors in deciding on the best medicine or treatment to use for certain individuals

• Identify gene changes that may increase the risk to develop a disease

• Identify gene changes that could be passed on to children

• Screen newborn babies for certain treatable conditions

Genetic test results can be hard to understand, however specialists like geneticists and genetic counselors can help explain what results might mean to you and your family. Because genetic testing tells you information about your DNA, which is shared with other family members, sometimes a genetic test result may have implications for blood relatives of the person who had testing.

What are the different types tests?

Diagnostic testing is used to precisely identify the disease that is making a person ill. The results of a diagnostic test may help you make choices about how to treat or manage your health.

Predictive and pre-symptomatic genetic tests are used to find gene changes that increase a person's likelihood of developing diseases. The results of these tests provide you with information about your risk of developing a specific disease. Such information may be useful in decisions about your lifestyle and healthcare.

Carrier testing is used to find people who "carry" a change in a gene that is linked to disease. Carriers may show no signs of the disease; however, they have the ability to pass on the gene change to their children, who may develop the disease or become carriers themselves. Some diseases require a gene change to be inherited from both parents for the disease to occur. This type of testing usually is offered to people who have a family history of a specific inherited disease or who belong to certain ethnic groups that have a higher risk of specific inherited diseases.

Prenatal testing is offered during pregnancy to help identify fetuses that have certain diseases.

Newborn screening is used to test babies one or two days after birth to find out if they have certain diseases known to cause problems with health and development.

Pharmacogenomic testing gives information about how certain medicines are processed by an individual's body. This type of testing can help your healthcare provider choose the medicines that work best with your genetic makeup.

Research genetic testing is used to learn more about the contributions of genes to health and to disease. Sometimes the results may not be directly helpful to participants, but they may benefit others by helping researchers expand their understanding of the human body, health, and disease.

What are the benefits and drawbacks?

Benefits: Genetic testing may be beneficial whether the test identifies a mutation or not. For some people, test results serve as a relief, eliminating some of the uncertainty surrounding their health. These results may also help doctors make recommendations for treatment or monitoring, and give people more information for making decisions about their and their family's health, allowing them to take steps to lower his/her chance of developing a disease. For example, as the result of such a finding, someone could be screened earlier and more frequently for the disease and/or could make changes to health habits like diet and exercise. Such a genetic test result can lower a person's feelings of uncertainty, and this information can also help people to make informed choices about their future, such as whether to have a baby.

Drawbacks: Genetic testing has a generally low risk of negatively impacting your physical health. However, it can be difficult financially or emotionally to find out your results.

Emotional: Learning that you or someone in your family has or is at risk for a disease can be scary. Some people can also feel guilty, angry, anxious, or depressed when they find out their results.

Financial: Genetic testing can cost anywhere from less than $100 to more than $2,000. Health insurance companies may cover part or all of the cost of testing.

Many people are worried about discrimination based on their genetic test results. In 2008, Congress enacted the Genetic Information Nondiscrimination Act (GINA) to protect people from discrimination by their health insurance provider or employer. GINA does not apply to long-term care, disability, or life insurance providers.

Limitations of testing: Genetic testing cannot tell you everything about inherited diseases. For example, a positive result does not always mean you will develop a disease, and it is hard to predict how severe symptoms may be. Geneticists and genetic counselors can talk more specifically about what a particular test will or will not tell you, and can help you decide whether to undergo testing.

How do I decide whether to be tested?

There are many reasons that people might get genetic testing. Doctors might suggest a genetic test if patients or their families have certain patterns of disease. Genetic testing is voluntary and the decision about whether to have genetic testing is complex.

A geneticist or genetic counselor can help families think about the benefits and limitations of a particular genetic test. Genetic counselors help individuals and families understand the scientific, emotional, and ethical factors surrounding the decision to have genetic testing and how to deal with the results of those tests.

Your doctor may suggest a genetic test to detect your risk of certain health problems, such as cancer. If you have symptoms of a disease, a genetic test may help with diagnosis.

Genetic testing looks for changes in genes. It’s usually done in a lab using a blood sample. Thousands of genetic tests are currently available.

Deciding whether to get a genetic test isn’t easy. It’s important to consider what you may learn. Test results can be a relief. They may give you peace of mind to know that you don’t carry a genetic change linked to a certain disease.

But test results can be alarming, too. Learning that you’re at risk of developing a certain disease may make the future seem uncertain. Keep in mind that such results may not mean that you’ll get that disease.

Genetic counselors are one type of health professional who can help you understand the risks and benefits of genetic testing. Your doctor may refer you to one. They can help you decide whether to undergo testing. And they can help explain what test results mean.

What are leukodystrophies?

Leukodystrophies are a group of rare genetic disorders that affect the central nervous system (CNS). The CNS is made up of your brain and spinal cord. Leukodystrophies damage the white matter of your CNS. The white matter includes

• Nerve fibers, also called axons, which connect your nerve cells
• Myelin, a layer of proteins and fatty materials that covers and protects the nerve fibers. It also helps speed up signals between the nerve cells.

When the white matter is damaged, it can slow down or block the signals between nerve cells. This can cause many different symptoms, including trouble with movement, vision, hearing, and thinking.

There are over 50 types of leukodystrophies. Some types are present at birth, while others may not cause symptoms until a child becomes a toddler. A few types mainly affect adults. Most types get worse over time.

What causes leukodystrophies?

Leukodystrophies are caused by genetic changes. These changes are usually inherited, meaning that they are passed from parent to child.

What are the symptoms of leukodystrophies?

The symptoms of leukodystrophies depend on the type; they can include a gradual loss of

• Muscle tone
• balance and mobility
• Walking
• Speech
• Ability to eat
• Vision
• Hearing
• Behavior

There can also be other symptoms, such as

• Learning disabilities
• bladder issues
• Breathing problems
• Developmental disabilities
• Muscle control disorders
• Seizures

How are leukodystrophies diagnosed?

Leukodystrophies can be hard to diagnose because there are so many different types which can have different symptoms. Your health care provider may use many tools to make a diagnosis:

• Physical and neurological exams
• A medical history, including asking about family history
• Imaging tests, such as an MRI or CT scan
• Genetic testing to look for genetic changes that could cause leukodystrophies
• Lab tests

What are the treatments for leukodystrophies?

There is no cure for leukodystrophies. Treatment focuses on relieving symptoms and providing support. It may include

• Medicines to manage muscle tone, seizures, and spasticity (muscle stiffness)
• Physical, occupational, and speech therapies to improve mobility, function, and cognitive problems
• Nutritional therapy for eating and swallowing problems
• Educational and recreational programs

Stem cell or bone marrow transplantation can be helpful for a few types of leukodystrophy.

One type of leukodystrophy, CTX, is treatable if it is diagnosed early. It is treated with chenodeoxycholic acid (CDCA) replacement therapy.

Metabolism is the process your body uses to make energy from the food you eat. Food is made up of proteins, carbohydrates, and fats. Chemicals in your digestive system (enzymes) break the food parts down into sugars and acids, your body's fuel. Your body can use this fuel right away, or it can store the energy in your body tissues. If you have a metabolic disorder, something goes wrong with this process.

Lipid metabolism disorders, such as Gaucher disease and Tay-Sachs disease, involve lipids. Lipids are fats or fat-like substances. They include oils, fatty acids, waxes, and cholesterol. If you have one of these disorders, you may not have enough enzymes to break down lipids. Or the enzymes may not work properly and your body can't convert the fats into energy. They cause a harmful amount of lipids to build up in your body. Over time, that can damage your cells and tissues, especially in the brain, peripheral nervous system, liver, spleen, and bone marrow. Many of these disorders can be very serious, or sometimes even fatal.

These disorders are inherited. Newborn babies get screened for some of them, using blood tests. If there is a family history of one of these disorders, parents can get genetic testing to see whether they carry the gene. Other genetic tests can tell whether the fetus has the disorder or carries the gene for the disorder.

Enzyme replacement therapies can help with a few of these disorders. For others, there is no treatment. Medicines, blood transfusions, and other procedures may help with complications.

Lipid storage diseases, or the lipidoses, are a group of inherited metabolic disorders in which harmful amounts of fatty materials (lipids) accumulate in various cells and tissues in the body. People with these disorders either do not produce enough of one of the enzymes needed to break down (metabolize) lipids or they produce enzymes that do not work properly. Over time, this excessive storage of fats can cause permanent cellular and tissue damage, particularly in the brain, peripheral nervous system (the nerves from the spinal cord to the rest of the body), liver, spleen, and bone marrow.

Lipids are fat-like substances that are important parts of the membranes found within and between cells and in the myelin sheath that coats and protects the nerves. Lipids include oils, fatty acids, waxes, steroids (such as cholesterol and estrogen), and other related compounds.

These fatty materials are stored naturally in the body’s cells, organs, and tissues. Tiny bodies within cells called lysosomes regularly convert, or metabolize, the lipids and proteins into smaller components to provide energy for the body. Disorders in which intracellular material that cannot be metabolized is stored in the lysosomes are called lysosomal storage diseases. In addition to lipid storage diseases, other lysosomal storage diseases include the mucolipidoses, in which excessive amounts of lipids with attached sugar molecules are stored in the cells and tissues, and the mucopolysaccharidoses, in which excessive amounts of large, complicated sugar molecules are stored.

Metabolism is the process your body uses to get or make energy from the food you eat. Food is made up of proteins, carbohydrates, and fats. Chemicals in your digestive system break the food parts down into sugars and acids, your body's fuel. Your body can use this fuel right away, or it can store the energy in your body tissues, such as your liver, muscles, and body fat.

A metabolic disorder occurs when abnormal chemical reactions in your body disrupt this process. When this happens, you might have too much of some substances or too little of other ones that you need to stay healthy. There are different groups of disorders. Some affect the breakdown of amino acids, carbohydrates, or lipids. Another group, mitochondrial diseases, affects the parts of the cells that produce the energy.

You can develop a metabolic disorder when some organs, such as your liver or pancreas, become diseased or do not function normally. Diabetes is an example.

Metabolism is the process your body uses to make energy from the food you eat. Food is made up of proteins, carbohydrates, and fats. Chemicals in your digestive system (enzymes) break the food parts down into sugars and acids, your body's fuel. Your body can use this fuel right away, or it can store the energy in your body tissues. If you have a metabolic disorder, something goes wrong with this process.

Mitochondrial diseases are a group of metabolic disorders. Mitochondria are small structures that produce energy in almost all of your cells. They make it by combining oxygen with the fuel molecules (sugars and fats) that come from your food. When the mitochondria are defective, the cells do not have enough energy. The unused oxygen and fuel molecules build up in the cells and cause damage.

The symptoms of mitochondrial disease can vary. It depends on how many mitochondria are defective, and where they are in the body. Sometimes only one organ, tissue, or cell type is affected. But often the problem affects many of them. Muscle and nerve cells have especially high energy needs, so muscular and neurological problems are common. The diseases range from mild to severe. Some types can be fatal.

Genetic mutations cause these diseases. They usually happen before age 20, and some are more common in infants. There are no cures for these diseases, but treatments may help with symptoms and slow down the disease. They may include physical therapy, vitamins and supplements, special diets, and medicines.

Mitochondrial genetic disorders refer to a group of conditions that affect the mitochondria (the structures in each cell of the body that are responsible for making energy). People with these conditions can present at any age with almost any affected body system; however, the brain, muscles, heart, liver, nerves, eyes, ears and kidneys are the organs and tissues most commonly affected.

Symptom severity can also vary widely. Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy. Those caused by mutations in mitochondrial DNA are transmitted by maternal inheritance, while those caused by mutations in nuclear DNA may follow an autosomal dominant, autosomal recessive, or X-linked pattern of inheritance. Treatment varies based on the specific type of condition and the signs and symptoms present in each person.

A champion swimmer, 16-year-old Joe Wise seems a healthy and happy high school junior. He enjoys time with friends, and he’s looking forward to college. But take a closer look, deep into his cells, and something’s not quite right. There’s a malfunction in the tiny capsule-shaped structures—called mitochondria —that power his cells. These abnormal mitochondria cause extreme fatigue and weakness in his legs, trouble breathing and a host of other problems.

“I used to play baseball, but now I can’t run so I can’t do that any more. Instead, I swim,” Joe says. In the past few years, he’s broken several national swimming records, and in 2008 he was on the U.S. Swim Team in the Beijing Paralympic games.

Joe is 1 of tens of thousands of people nationwide who have mitochondrial diseases, although estimates vary. There are dozens of subtypes, with each affecting less than 1 in 1,500 people. There’s no treatment or cure for any of these rare diseases.

Mitochondrial diseases are caused by abnormal genes that lead to flawed proteins or other molecules in the mitochondria. The various subtypes are caused by alterations in different genes, leading to worn-down cells in different parts of the body. Hardest hit are organs and tissues that need a lot of energy, like muscles, brain, heart, kidneys and liver. When the energy supply slumps, cells can become damaged or destroyed.

But mitochondria have importance beyond rare diseases. Even in healthy people, researchers have found, mitochondria can gradually deteriorate as we grow older. Malfunctioning mitochondria have been linked to diabetes, heart disease, Alzheimer’s disease, Parkinson’s disease and even normal aging. “If we can learn more about the rare mitochondrial disorders, the findings could have implications for understanding more common diseases,” says Dr. Vamsi Mootha of Harvard Medical School.

The rare mitochondrial diseases are notoriously difficult for doctors to recognize and diagnose. Depending on which cells are affected, people with mitochondrial diseases may have muscle weakness and pain, digestive problems, heart disease, seizures and many other symptoms. These diseases affect both children and adults. Some lead to early death. Because the symptoms vary widely, mitochondrial diseases are often mistaken for other conditions.

In Joe Wise’s case, he was an avid baseball and football player before age 8, when his father noticed he was walking and running a little funny. He felt tired and weak. He had trouble swallowing. Joe’s parents took him to see several specialists, who thought he might have juvenile arthritis, muscular dystrophy or maybe a problem with his hip. But eventually, a muscle biopsy showed that he had mitochondrial disease. His doctors didn’t expect him to live beyond age 14. “It was a real shock to the family,” Joe says. “It was something we suddenly had to learn a lot more about.”

Joe had to make difficult adjustments—watching his diet, being careful while walking and using a ventilator twice a day and overnight to help him breathe. He finds he feels weaker over time but continues to swim just about every day. “Swimming has helped in a lot of different ways,” Joe says. “It’s kept me out of a wheelchair. It’s kept me off a larger ventilator.” He’s now in training for the 2012 Paralympics.

Scientists don’t yet know why some patients like Joe can continue to exercise, while others have more severe disabilities. Over the last decades, though, researchers have learned a lot about mitochondria.

Each cell in the body contains dozens or even hundreds of mitochondria. Mitochondria produce about 90% of the energy that cells need to function. They differ from other cell components because each contains its own tiny loops of DNA, called mtDNA. The circular mtDNA differs from the well-known long DNA strands that make up the chromosomes contained in the control center, or nucleus, of your cells. Your nuclear DNA comes from both your mother and your father, but mtDNA comes only from your mother.

Scientists have learned that among the genes in mtDNA are instructions for making 13 proteins that mitochondria need to produce energy. Mutations in these genes can lead to dozens of different diseases.

But mitochondria contain much more than 13 proteins. They also contain over 1,000 proteins that come from genes in the cell’s nucleus. “We now know that the vast majority of genetic mitochondrial disorders are actually due to mutations in the nuclear genome ,” says Mootha.

These nuclear mutations are difficult to identify. While some research centers can now sequence the entire mtDNA and find the mutations that cause a patient’s disease, that can’t be done for most mutations in nuclear DNA.

Over the past 7 years, Mootha and his colleagues have been working to change that. They’ve used powerful new research tools to identify about 1,100 genes in our nuclear DNA that make proteins found in mitochondria. They’re now searching for mutations in these genes in patients who have mitochondrial disease. That will help with developing diagnostics, he says. “And once we know the molecular underpinnings of these disorders, they may offer clues for completely new treatment strategies.”

Several potential therapies for mitochondrial diseases are already being explored. Some patients with mtDNA mutations have a mix of normal and mutant mtDNA in their cells. Researchers are searching for ways to shift the balance toward more normal DNA. At the University of Texas Southwestern Medical School, Dr. Ronald Haller is testing to see if endurance training can safely encourage this shift, or at least improve physical health, in patients with mtDNA mutations.

“The benefits of exercise training in healthy people are well-recognized,” Haller says. One benefit is to increase the number of mitochondria in your muscles. “We want to see if some of these same benefits extend to patients with mitochondrial disease.”

Haller and his colleagues have already conducted small studies that suggest patients who train can improve their ability to walk and do other daily activities. He’s also found evidence that mitochondrial numbers shrink once patients stop training—which also happens in healthy people. Haller has now begun a larger study of 40 patients to see how exercise training, and taking a break from exercise, affect mitochondria and exercise capacity.

“A lot of exciting new research in mitochondrial biology is taking place right now,” says Mootha. “As we learn more about these disorders, we’ll hopefully be able to convert this knowledge into better therapies.”

Mitochondrial Disease Symptoms

Mitochondrial disease can affect different parts of the body. Symptoms can range from mild to severe and might include:

• Poor growth
• Muscle weakness or fatigue
• Visual or hearing problems
• Mental retardation
• Heart, liver or kidney disease
• Digestive problems
• Breathing difficulties
• Diabetes
• Seizures

Q: What are mitochondrial diseases or disorders?

A: Mitochondria are tiny parts of almost every cell in your body. Mitochondria are like the power house of the cells. They turn sugar and oxygen into energy that the cells need to work.

In mitochondrial diseases, the mitochondria cannot efficiently turn sugar and oxygen into energy, so the cells do not work correctly.

There are many types of mitochondrial disease, and they can affect different parts of the body: the brain, kidneys, muscles, heart, eyes, ears, and others. Mitochondrial diseases can affect one part of the body or can affect many parts. They can affect those part(s) mildly or very seriously.

Not everyone with a mitochondrial disease will show symptoms. However, when discussing the group of mitochondrial diseases that tend to affect children, symptoms usually appear in the toddler and preschool years.

Mitochondrial diseases and disorders are the same thing.

Q: Is there a relationship between mitochondrial disease and autism?

A: A child with a mitochondrial disease:

• may also have an autism spectrum disorder,
• may have some of the symptoms/signs of autism, or
• may not have any signs or symptoms related to autism.

A child with autism may or may not have a mitochondrial disease. When a child has both autism and a mitochondrial disease, they sometimes have other problems as well, including epilepsy, problems with muscle tone, and/or movement disorders.

More research is needed to find out how common it is for people to have autism and a mitochondrial disorder. Right now, it seems rare. In general, more research about mitochondrial disease and autism is needed.

Q: What is regressive encephalopathy?

A: Encephalopathy is a medical term for a disease or disorder of the brain. It usually means a slowing down of brain function.

Regression happens when a person loses skills that they used to have like walking or talking or even being social.

Regressive encephalopathy means there is a disease or disorder in the brain that makes a person lose skills they once had.

We know that sometimes children with mitochondrial diseases seem to be developing as they should, but around toddler or preschool age, they regress. The disease was there all the time, but something happens that “sets it off”. This could be something like malnutrition, an illness such as flu, a high fever, dehydration, or it could be something else.

Q: Is there a relationship between autism and encephalopathy?

A: Most children with an autism spectrum disorder do not and have not had an encephalopathy. Some children with an autism spectrum disorder have had regression and some have had a regressive encephalopathy.

Q: What do we know about the relationship between mitochondrial disease and other disorders related to the brain?

A: Different parts of the brain have different functions. The area of the brain that is damaged by a mitochondrial disease determines how the person is impacted. This means that a person could have seizures; trouble talking or interacting with people; difficulty eating; muscle weakness, or other problems. They could have one issue or several.

Q: Do vaccines cause or worsen mitochondrial diseases?

A: As of now, there are no scientific studies that say vaccines cause or worsen mitochondrial diseases. We do know that certain illnesses that can be prevented by vaccines, such as the flu, can trigger the regression that is related to a mitochondrial disease. More research is needed to determine if there are rare cases where underlying mitochondrial disorders are triggered by anything related to vaccines. However, we know that for most children, vaccines are a safe and important way to prevent them from getting life-threatening diseases.

Q: Are all children routinely tested for mitochondrial diseases? What about children with autism?

A: Children are not routinely tested for mitochondrial diseases. This includes children with autism and other developmental delays.

Testing is not easy and may involve getting multiple samples of blood, and often samples of muscle. Doctors decide whether testing for mitochondrial diseases should be done based on a child’s signs and symptoms.

Q: Should I have my child tested for a mitochondrial disease?

A: If you are worried that your child might have a mitochondrial disease, talk to your child’s doctor.

Phenylketonuria (PKU) is a type of amino acid metabolism disorder. It is inherited. If you have it, your body can't process phenylalanine (Phe). Phe is an amino acid, a building block of proteins. It is in almost all foods. If your Phe level gets too high, it can damage your brain and cause severe intellectual disability. All babies born in U.S. hospitals must now have a screening test for PKU. This makes it easier to diagnose and treat the problem early.

The best treatment for PKU is a diet of low-protein foods. There are special formulas for newborns. For older children and adults, the diet includes many fruits and vegetables. It also includes some low-protein breads, pastas, and cereals. Nutritional formulas provide the vitamins and minerals you can't get from their food.

Babies who get on this special diet soon after they are born develop normally. Many have no symptoms of PKU. It is important to stay on the diet for the rest of your life.

Phenylketonuria is an inherited disorder of metabolism that causes an increase in the blood of a chemical known as phenylalanine.

What is phenylketonuria (PKU)?

Phenylketonuria (PKU) is an inherited disorder of metabolism that causes an increase in the blood of a chemical known as phenylalanine. Phenylalanine comes from a person's diet and is used by the body to make proteins. Phenylalanine is found in all food proteins and in some artificial sweeteners. Without dietary treatment, phenylalanine can build up to harmful levels in the body, causing mental disability and other serious problems.

Women who have high levels of phenylalanine during pregnancy are at high risk for having babies born with mental disability, heart problems, small head size (microcephaly) and developmental delay. This is because the babies are exposed to their mother's very high levels of phenylalanine before they are born.

In the United States, PKU occurs in 1 in 10,000 to 1 in 15,000 newborn babies. Newborn screening has been used to detect PKU since the 1960's. As a result, the severe signs and symptoms of PKU are rarely seen.

What are the symptoms of PKU?

Symptoms of PKU range from mild to severe. Severe PKU is called classic PKU. Infants born with classic PKU appear normal for the first few months after birth. However, without treatment with a low-phenylalanine diet, these infants will develop mental retardation and behavioral problems. Other common symptoms of untreated classic PKU include seizures, developmental delay, and autism. Boys and girls who have classic PKU may also have eczema of the skin and lighter skin and hair than their family members who do not have PKU.

Babies born with less severe forms of PKU (moderate or mild PKU) may have a milder degree of mental retardation unless treated with the special diet. If the baby has only a very slight degree of PKU, often called mild hyperphenylalaninemia, there may be no problems and the special dietary treatment may not be needed.

How is PKU diagnosed?

PKU is usually diagnosed through newborn screening testing that is done shortly after birth on a blood sample (heel stick). However, PKU should be considered at any age in a person who has developmental delays or mental retardation. This is because, rarely, infants are missed by newborn screening programs.

What is the treatment for PKU?

PKU is treated by limiting the amount of protein (that contains phenylalanine) in the diet. Treatment also includes using special medical foods as well as special low-protein foods and taking vitamins and minerals. People who have PKU need to follow this diet for their lifetime. It is especially important for women who have PKU to follow the diet throughout their childbearing years.

Is PKU inherited?

PKU is inherited in families in an autosomal recessive pattern. Autosomal recessive inheritance means that a person has two copies of the gene that is altered. Usually, each parent of an individual who has PKU carries one copy of the altered gene. Since each parent also has a normal gene, they do not show signs or symptoms of PKU.

Gene alterations (mutations) in the PAH gene cause PKU. Mutations in the PAH gene cause low levels of an enzyme called phenylalanine hydroxylase. These low levels mean that phenylalanine from a person's diet cannot be metabolized (changed), so it builds up to toxic levels in the bloodstream and body. Having too much phenylalanine can cause brain damage unless diet treatment is started.

Phenylketonuria (pronounced fen-l-kee-toh-NOOR-ee-uh), often called PKU, is an inherited disorder that that can cause intellectual and developmental disabilities (IDDs) if not treated. In PKU, the body can't process a portion of a protein called phenylalanine, which is in all foods containing protein. If the phenylalanine level gets too high, the brain can become damaged.

All children born in U.S. hospitals are tested routinely for PKU soon after birth, making it easier to diagnose and treat affected children early.

Children and adults who are treated early and consistently develop normally.

Depending on the level of phenylalanine and tolerance for phenylalanine in the diet, PKU is classified into two different types: classic, which is the severe form, and moderate. Therefore, each patient needs an individualized treatment plan. Some people may benefit from a medication called sapropterin dihydrochloride (brand name Kuvan®) that treats the disorder.