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.

Alkalosis is a condition in which the blood and other body fluids are too alkaline (basic). As with acidosis, respiratory disorders are a major cause; however, in respiratory alkalosis, carbon dioxide levels fall too low. Lung disease, aspirin overdose, shock, and ordinary anxiety can cause respiratory alkalosis, which reduces the normal concentration of H⁺.

Metabolic alkalosis often results from prolonged, severe vomiting, which causes a loss of hydrogen and chloride ions (as components of HCl). Medications also can prompt alkalosis. These include diuretics that cause the body to lose potassium ions, as well as antacids when taken in excessive amounts, for instance by someone with persistent heartburn or an ulcer.

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.

Amyloidosis occurs when abnormal proteins called amyloids build up and form deposits. The deposits can collect in organs such as the kidney and heart. This can cause the organs to become stiff and unable to work the way they should.

There are three main types of amyloidosis:

• Primary - with no known cause
• Secondary - caused by another disease, including some types of cancer
• Familial - passed down through genes

Symptoms can vary, depending upon which organs are affected. Treatment depends on the type of amyloidosis you have. The goal is to help with symptoms and limit the production of proteins. If another disease is the cause, it needs to be treated.

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.

Normal arterial blood pH is restricted to a very narrow range of 7.35 to 7.45. A person who has a blood pH below 7.35 is considered to be in acidosis (actually, “physiological acidosis,” because blood is not truly acidic until its pH drops below 7), and a continuous blood pH below 7.0 can be fatal. Acidosis has several symptoms, including headache and confusion, and the individual can become lethargic and easily fatigued (Figure 26.18). A person who has a blood pH above 7.45 is considered to be in alkalosis, and a pH above 7.8 is fatal. Some symptoms of alkalosis include cognitive impairment (which can progress to unconsciousness), tingling or numbness in the extremities, muscle twitching and spasm, and nausea and vomiting. Both acidosis and alkalosis can be caused by either metabolic or respiratory disorders.

As discussed earlier in this chapter, the concentration of carbonic acid in the blood is dependent on the level of CO₂ in the body and the amount of CO₂ gas exhaled through the lungs. Thus, the respiratory contribution to acid-base balance is usually discussed in terms of CO₂ (rather than of carbonic acid). Remember that a molecule of carbonic acid is lost for every molecule of CO₂ exhaled, and a molecule of carbonic acid is formed for every molecule of CO₂ retained.

Figure 26.18 Symptoms of Acidosis and Alkalosis Symptoms of acidosis affect several organ systems. Both acidosis and alkalosis can be diagnosed using a blood test.

Metabolic Acidosis: Primary Bicarbonate Deficiency

Metabolic acidosis occurs when the blood is too acidic (pH below 7.35) due to too little bicarbonate, a condition called primary bicarbonate deficiency. At the normal pH of 7.40, the ratio of bicarbonate to carbonic acid buffer is 20:1. If a person’s blood pH drops below 7.35, then the person is in metabolic acidosis. The most common cause of metabolic acidosis is the presence of organic acids or excessive ketone bodies in the blood. Table 26.2 lists some other causes of metabolic acidosis.

Common Causes of Metabolic Acidosis and Blood Metabolites

Table 26.2 *Acid metabolites from ingested chemical.

The first three of the eight causes of metabolic acidosis listed are medical (or unusual physiological) conditions. Strenuous exercise can cause temporary metabolic acidosis due to the production of lactic acid. The last five causes result from the ingestion of specific substances. The active form of aspirin is its metabolite, sulfasalicylic acid. An overdose of aspirin causes acidosis due to the acidity of this metabolite. Metabolic acidosis can also result from uremia, which is the retention of urea and uric acid. Metabolic acidosis can also arise from diabetic ketoacidosis, wherein an excess of ketone bodies are present in the blood. Other causes of metabolic acidosis are a decrease in the excretion of hydrogen ions, which inhibits the conservation of bicarbonate ions, and excessive loss of bicarbonate ions through the gastrointestinal tract due to diarrhea.

Metabolic Alkalosis: Primary Bicarbonate Excess

Metabolic alkalosis is the opposite of metabolic acidosis. It occurs when the blood is too alkaline (pH above 7.45) due to too much bicarbonate (called primary bicarbonate excess).

A transient excess of bicarbonate in the blood can follow ingestion of excessive amounts of bicarbonate, citrate, or antacids for conditions such as stomach acid reflux—known as heartburn. Cushing’s disease, which is the chronic hypersecretion of adrenocorticotropic hormone (ACTH) by the anterior pituitary gland, can cause chronic metabolic alkalosis. The oversecretion of ACTH results in elevated aldosterone levels and an increased loss of potassium by urinary excretion. Other causes of metabolic alkalosis include the loss of hydrochloric acid from the stomach through vomiting, potassium depletion due to the use of diuretics for hypertension, and the excessive use of laxatives.

Respiratory Acidosis: Primary Carbonic Acid/CO₂ Excess

Respiratory acidosis occurs when the blood is overly acidic due to an excess of carbonic acid, resulting from too much CO₂ in the blood. Respiratory acidosis can result from anything that interferes with respiration, such as pneumonia, emphysema, or congestive heart failure.

Respiratory Alkalosis: Primary Carbonic Acid/CO₂ Deficiency

Respiratory alkalosis occurs when the blood is overly alkaline due to a deficiency in carbonic acid and CO₂ levels in the blood. This condition usually occurs when too much CO₂ is exhaled from the lungs, as occurs in hyperventilation, which is breathing that is deeper or more frequent than normal. An elevated respiratory rate leading to hyperventilation can be due to extreme emotional upset or fear, fever, infections, hypoxia, or abnormally high levels of catecholamines, such as epinephrine and norepinephrine. Surprisingly, aspirin overdose—salicylate toxicity—can result in respiratory alkalosis as the body tries to compensate for initial acidosis.

Compensation Mechanisms

Various compensatory mechanisms exist to maintain blood pH within a narrow range, including buffers, respiration, and renal mechanisms. Although compensatory mechanisms usually work very well, when one of these mechanisms is not working properly (like kidney failure or respiratory disease), they have their limits. If the pH and bicarbonate to carbonic acid ratio are changed too drastically, the body may not be able to compensate. Moreover, extreme changes in pH can denature proteins. Extensive damage to proteins in this way can result in disruption of normal metabolic processes, serious tissue damage, and ultimately death.

Respiratory Compensation

Respiratory compensation for metabolic acidosis increases the respiratory rate to drive off CO₂ and readjust the bicarbonate to carbonic acid ratio to the 20:1 level. This adjustment can occur within minutes. Respiratory compensation for metabolic alkalosis is not as adept as its compensation for acidosis. The normal response of the respiratory system to elevated pH is to increase the amount of CO₂ in the blood by decreasing the respiratory rate to conserve CO₂. There is a limit to the decrease in respiration, however, that the body can tolerate. Hence, the respiratory route is less efficient at compensating for metabolic alkalosis than for acidosis.

Metabolic Compensation

Metabolic and renal compensation for respiratory diseases that can create acidosis revolves around the conservation of bicarbonate ions. In cases of respiratory acidosis, the kidney increases the conservation of bicarbonate and secretion of H⁺ through the exchange mechanism discussed earlier. These processes increase the concentration of bicarbonate in the blood, reestablishing the proper relative concentrations of bicarbonate and carbonic acid. In cases of respiratory alkalosis, the kidneys decrease the production of bicarbonate and reabsorb H⁺ from the tubular fluid. These processes can be limited by the exchange of potassium by the renal cells, which use a K⁺-H⁺ exchange mechanism (antiporter).

Diagnosing Acidosis and Alkalosis

Lab tests for pH, CO₂ partial pressure (PCO₂),and HCO₃^– can identify acidosis and alkalosis, indicating whether the imbalance is respiratory or metabolic, and the extent to which compensatory mechanisms are working. The blood pH value, as shown in Table 26.3, indicates whether the blood is in acidosis, the normal range, or alkalosis. The PCO₂ and total HCO₃^– values aid in determining whether the condition is metabolic or respiratory, and whether the patient has been able to compensate for the problem. Table 26.3 lists the conditions and laboratory results that can be used to classify these conditions. Metabolic acid-base imbalances typically result from kidney disease, and the respiratory system usually responds to compensate.

Types of Acidosis and Alkalosis

Table 26.3 Reference values (arterial): pH: 7.35–7.45; pCO₂: male: 35–48 mm Hg, female: 32–45 mm Hg; total venous bicarbonate: 22–29 mM. N denotes normal; ↑ denotes a rising or increased value; and ↓ denotes a falling or decreased value.

Metabolic acidosis is problematic, as lower-than-normal amounts of bicarbonate are present in the blood. The PCO₂ would be normal at first, but if compensation has occurred, it would decrease as the body reestablishes the proper ratio of bicarbonate and carbonic acid/CO₂.

Respiratory acidosis is problematic, as excess CO₂ is present in the blood. Bicarbonate levels would be normal at first, but if compensation has occurred, they would increase in an attempt to reestablish the proper ratio of bicarbonate and carbonic acid/CO₂.

Alkalosis is characterized by a higher-than-normal pH. Metabolic alkalosis is problematic, as elevated pH and excess bicarbonate are present. The PCO₂ would again be normal at first, but if compensation has occurred, it would increase as the body attempts to reestablish the proper ratios of bicarbonate and carbonic acid/CO₂.

Respiratory alkalosis is problematic, as CO₂ deficiency is present in the bloodstream. The bicarbonate concentration would be normal at first. When renal compensation occurs, however, the bicarbonate concentration in blood decreases as the kidneys attempt to reestablish the proper ratios of bicarbonate and carbonic acid/CO₂ by eliminating more bicarbonate to bring the pH into the physiological range.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a genetic disorder that is most common in males. About 1 in 10 African American males in the United States has it. G6PD deficiency mainly affects red blood cells, which carry oxygen from the lungs to tissues throughout the body. The most common medical problem it can cause is hemolytic anemia. That happens when red blood cells are destroyed faster than the body can replace them.

If you have G6PD deficiency, you may not have symptoms. Symptoms happen if your red blood cells are exposed to certain chemicals in food or medicine, certain bacterial or viral infections, or stress. They may include

• Paleness
• Jaundice
• Dark urine
• Fatigue
• Shortness of breath
• Enlarged spleen
• Rapid heart rate

A blood test can tell if you have it. Treatments include medicines to treat infection, avoiding substances that cause the problem with red blood cells, and sometimes transfusions.

Gaucher disease is an inherited disorder that affects many of the body's organs and tissues. The signs and symptoms of this condition vary widely among affected individuals. Researchers have described several types of Gaucher disease based on their characteristic features.

Type 1 Gaucher disease is the most common form of this condition. Type 1 is also called non-neuronopathic Gaucher disease because the brain and spinal cord (the central nervous system) are usually not affected. The features of this condition range from mild to severe and may appear anytime from childhood to adulthood. Major signs and symptoms include enlargement of the liver and spleen (hepatosplenomegaly), a low number of red blood cells (anemia), easy bruising caused by a decrease in blood platelets (thrombocytopenia), bone abnormalities such as bone pain and fractures, and joint conditions such as arthritis.

Types 2 and 3 Gaucher disease are known as neuronopathic forms of the disorder because they are characterized by problems that affect the central nervous system. In addition to the signs and symptoms described above, these conditions can cause abnormal eye movements, seizures, and brain damage. Type 2 Gaucher disease usually causes life-threatening medical problems beginning in infancy. Type 3 Gaucher disease also affects the nervous system, but it tends to worsen more slowly than type 2.

The most severe type of Gaucher disease is a very rare form of type 2 called the perinatal lethal form. This condition causes severe or life-threatening complications starting before birth or in infancy. Features of the perinatal lethal form can include extensive swelling caused by fluid accumulation before birth (hydrops fetalis); dry, scaly skin (ichthyosis) or other skin abnormalities; hepatosplenomegaly; distinctive facial features; and serious neurological problems. As its name indicates, most infants with the perinatal lethal form of Gaucher disease survive for only a few days after birth.

Another form of Gaucher disease is known as the cardiovascular type (or type 3c) because it primarily affects the heart, causing the heart valves to harden (calcify). People with the cardiovascular form of Gaucher disease may also have eye abnormalities, bone disease, and mild enlargement of the spleen (splenomegaly).

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.

Hemochromatosis is a disease in which too much iron builds up in your body. Your body needs iron but too much of it is toxic. If you have hemochromatosis, you absorb more iron than you need. Your body has no natural way to get rid of the extra iron. It stores it in body tissues, especially the liver, heart, and pancreas. The extra iron can damage your organs. Without treatment, it can cause your organs to fail.

There are two types of hemochromatosis. Primary hemochromatosis is an inherited disease. Secondary hemochromatosis is usually the result of something else, such as anemia, thalassemia, liver disease, or blood transfusions.

Many symptoms of hemochromatosis are similar to those of other diseases. Not everyone has symptoms. If you do, you may have joint pain, fatigue, general weakness, weight loss, and stomach pain.

Your doctor will diagnose hemochromatosis based on your medical and family histories, a physical exam, and the results from tests and procedures. Treatments include removing blood (and iron) from your body, medicines, and changes in your diet.

Homocystinuria is an inherited disorder in which the body is unable to process certain building blocks of proteins (amino acids) properly.

The most common form of homocystinuria, called classic homocystinuria, is characterized by tall stature, nearsightedness (myopia), dislocation of the lens at the front of the eye, a higher risk of blood clotting disorders, and brittle bones that are prone to fracture (osteoporosis) or other skeletal abnormalities. Some affected individuals also have developmental delay and learning problems.

Less common forms of homocystinuria can cause intellectual disability, slower growth and weight gain (failure to thrive), seizures, and problems with movement. They can also cause and a blood disorder called megaloblastic anemia, which occurs when a person has a low number of red blood cells (anemia), and the remaining red blood cells are larger than normal (megaloblastic).

The signs and symptoms of homocystinuria typically develop during childhood, although some mildly affected people may not show signs and symptoms until adulthood.

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.

Your small intestine does most of the digesting of the foods you eat. If you have a malabsorption syndrome, your small intestine cannot absorb nutrients from foods.

Causes of malabsorption syndromes include

• Celiac disease
• Lactose intolerance
• Short bowel syndrome. This happens after surgery to remove half or more of the small intestine. You might need the surgery if you have a problem with the small intestine from a disease, injury, or birth defect.
• Whipple disease, a rare bacterial infection
• Genetic diseases
• Certain medicines

Symptoms of different malabsorption syndromes can vary. They often include chronic diarrhea, abnormal stools, weight loss, and gas. Your doctor may use lab, imaging, or other tests to make a diagnosis.

Treatment of malabsorption syndromes depends on the cause.

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.

Is genetic testing for PKU available?

A blood sample can be used to test for the mutations that cause PKU.

Testing an Infant

A blood test that measures the phenylalanine in an infant's blood is enough to help make a PKU diagnosis. Therefore, DNA testing is not necessary. However, if a child tests positive for PKU, health care providers may recommend genetic testing because identifying the type of mutation involved can help guide selection of the most appropriate treatment plan.

A DNA test also should be performed on a child if both parents are PKU carriers and the standard newborn blood test does not show the condition. The test will definitively indicate or rule out PKU, if the disease-causing mutations in the family have been identified.

Testing During Pregnancy

A pregnant woman can request a prenatal DNA test to learn whether or not her child will be born with PKU. To perform this test, a health care provider takes some cells, either through a needle inserted into the abdomen or a small tube inserted into the vagina. A genetic counselor who understands the risks and benefits of genetic testing can help explain the choices available for testing.1 This discussion may be particularly useful for parents who already have one child with PKU, because they have a higher-than-average chance of conceiving another child with the disorder. The disease causing mutations must have been identified before prenatal testing can be performed.

Testing Possible PKU Carriers

If a child is diagnosed with PKU, other family members may be more likely to conceive children who also will have PKU. The parents' siblings and other close blood relatives should be told that the child has PKU so that they can decide whether or not they should have DNA testing as well.

What is maternal PKU?

Maternal PKU is the term used when a woman who has PKU becomes pregnant. Most children born to PKU mothers do not have the disorder. But if a pregnant woman who has PKU does not strictly follow a low-phenylalanine diet, her child can develop serious problems. These include:

• Intellectual disabilities
• Having a head that is too small (microcephaly)
• Heart defects
• Low birth weight
• Behavioral problems

The newborn’s problems from untreated maternal PKU are caused by the high phenylalanine levels present in the mother’s blood during pregnancy—not by PKU itself. The infant does not have PKU and does not need a PKU diet. The PKU diet will not help these health problems.

Women with PKU and uncontrolled phenylalanine levels also have an increased risk of pregnancy loss.

If I have PKU, what steps should I take during pregnancy to protect my infant?

If you have PKU, it is very important to follow a strict low-phenylalanine diet before becoming pregnant and throughout your pregnancy.

In addition to staying on a PKU diet, also make sure to:

• Visit a PKU clinic on a regular basis
• Have your blood checked often for phenylalanine
• Ask your health care provider how much PKU formula to drink

Keep in mind that untreated maternal PKU can cause serious problems for a developing fetus.

A newborn’s problems from untreated maternal PKU are caused by the high phenylalanine levels present in the mother’s blood during pregnancy—not PKU itself. The infant does not have PKU and does not need a PKU diet. The PKU diet will not help these health problems.

Women with PKU and uncontrolled phenylalanine levels also have an increased risk of pregnancy loss.

What determines the severity of PKU?

A number of factors influence whether a person with PKU has mild symptoms or more severe problems.

Genetic Factors

Many different mutations of the PAH gene can cause PKU. The type of mutation greatly affects the severity of the person's symptoms.

Some mutations cause classic PKU, the most severe form of the disorder. In these cases, the enzyme that breaks down phenylalanine barely works or does not work at all. If it is not treated, classic PKU can cause severe brain damage and other serious medical problems. Some mutations allow the enzyme to work a little better than it does in classic PKU. This is sometimes called non-PKU hyperphenylalaninemia, and is also known as non-PKU HPA. Such cases come with a smaller risk of brain damage. People with very mild cases may not require treatment with a low-phenylalanine diet.

Non-genetic Factors

Genes are not the only factor that influences the severity of PKU symptoms. For example, strictly following a PKU diet greatly reduces the chances that a person will have intellectual disabilities and other problems caused by PKU. Other factors include the person's age at diagnosis and how quickly the person's blood levels of phenylalanine are brought under control.

Does a child with PKU need repeated testing?

Infants and children with PKU need frequent blood tests to measure the phenylalanine in their blood. The health care provider may suggest changes to the diet or formula the child receives if there is evidence of too much or too little phenylalanine.

Infants with PKU will be tested about once a week for the first year of their lives. After the first year, children may be tested once or twice a month. Adults also need to be checked regularly throughout their lives. Often, blood samples can be taken at home and mailed to a laboratory.

Porphyrias are a group of genetic disorders caused by problems with how your body makes a substance called heme. Heme is found throughout the body, especially in your blood and bone marrow, where it carries oxygen.

There are two main types of porphyrias. One affects the skin and the other affects the nervous system. People with the skin type develop blisters, itching, and swelling of their skin when it is exposed to sunlight. The nervous system type is called acute porphyria. Symptoms include pain in the chest, abdomen, limbs, or back; muscle numbness, tingling, paralysis, or cramping; vomiting; constipation; and personality changes or mental disorders. These symptoms come and go.

Certain triggers can cause an attack, including some medicines, smoking, drinking alcohol, infections, stress, and sun exposure. Attacks develop over hours or days. They can last for days or weeks.

Porphyria can be hard to diagnose. It requires blood, urine, and stool tests. Each type of porphyria is treated differently. Treatment may involve avoiding triggers, receiving heme through a vein, taking medicines to relieve symptoms, or having blood drawn to reduce iron in the body. People who have severe attacks may need to be hospitalized.

Porphyrias are rare disorders that mainly affect the skin or nervous system. These disorders are usually inherited, meaning they are caused by gene mutations passed from parents to children.

If you have porphyria, cells fail to change chemicals in your body—called porphyrins and porphyrin precursors—into heme, the substance that gives blood its red color. When these chemicals build up in your body, they cause illness. Depending on the type of porphyria you have, porphyrins or porphyrin precursors may build up in the liver or the bone marrow. Bone marrow is the spongy tissue inside most of your bones.

Heme is a red pigment composed of iron linked to a chemical called protoporphyrin. Heme has important functions in the body. The largest amounts of heme are in the form of hemoglobin, found in red blood cells and bone marrow. Hemoglobin carries oxygen from the lungs to all parts of the body. In the liver, heme is a component of proteins that break down hormones, medications, and other chemicals and keep liver cells functioning normally. Heme is an important part of nearly every cell in the body.

Porphyrias are rare diseases. Studies suggest that all types of porphyrias combined affect fewer than 200,000 people in the United States.

The most common type of acute porphyria is acute intermittent porphyria.

The most common type of cutaneous porphyria—and the most common type of porphyria overall—is porphyria cutanea tarda, which affects about 5 to 10 out of every 100,000 people.

The most common type of porphyria in children is a cutaneous porphyria called erythropoietic protoporphyria.

The porphyrias are a group of different diseases, each caused by a specific abnormality in the heme production process.

What is porphyria?

The porphyrias are a group of different diseases, each caused by a specific abnormality in the heme production process. Heme is a chemical compound that contains iron and gives blood its red color. The essential functions of heme depend on its ability to bind oxygen. Heme is incorporated into hemoglobin, a protein that enables red blood cells to carry oxygen from the lungs to all parts of the body. Heme also plays a role in the liver where it assists in breaking down chemicals (including some drugs and hormones) so that they are easily removed from the body.

Heme is produced in the bone marrow and liver through a complex process controlled by eight different enzymes. As this production process of heme progresses, several different intermediate compounds (heme precursors) are created and modified. If one of the essential enzymes in heme production is deficient, certain precursors may accumulate in tissues (especially in the bone marrow or liver), appear in excess in the blood, and get excreted in the urine or stool. The specific precursors that accumulate depend on which enzyme is deficient. Porphyria results in a deficiency or inactivity of a specific enzyme in the heme production process, with resulting accumulation of heme precursors.

How is porphyria diagnosed?

Porphyria is diagnosed through blood, urine, and stool tests, especially at or near the time of symptoms. Diagnosis may be difficult because the range of symptoms is common to many disorders and interpretation of the tests may be complex. A large number of tests are available, however, but results among laboratories are not always reliable.

How is porphyria treated?

Each form of porphyria is treated differently. Treatment may involve treating with heme, giving medicines to relieve the symptoms, or drawing blood. People who have severe attacks may need to be hospitalized.

What are the signs and symptoms of porphyria?

The signs and symptoms of porphyria vary among types. Some types of porphyria (called cutaneous porphyria) cause the skin to become overly sensitive to sunlight. Areas of the skin exposed to the sun develop redness, blistering and often scarring.

The symptoms of other types of porphyria (called acute porphyrias) affect the nervous system. These symptoms include chest and abdominal pain, emotional and mental disorders, seizures and muscle weakness. These symptoms often appear quickly and last from days to weeks. Some porphyrias have a combination of acute symptoms and symptoms that affect the skin.

Environmental factors can trigger the signs and symptoms of porphyria. These include:

• Alcohol

• Smoking

• Certain drugs, hormones

• Exposure to sunlight

• Stress

• Dieting and fasting

What do we know about porphyria and heredity?

Most of the porphyrias are inherited conditions. The genes for all the enzymes in the heme pathway have been identified. Some forms of porphyria result from inheriting one altered gene from one parent (autosomal dominant). Other forms result from inheriting two altered genes, one from each parent (autosomal recessive). Each type of porphyria carries a different risk that individuals in an affected family will have the disease or transmit it to their children.

Porphyria cutanea tarda (PCT) is a type of porphyria that is most often not inherited. Eighty percent of individuals with PCT have an acquired disease that becomes active when factors such as iron, alcohol, hepatitis C virus (HCV), HIV, estrogens (such as those used in oral contraceptives and prostate cancer treatment), and possibly smoking, combine to cause an enzyme deficiency in the liver. Hemochromatosis, an iron overload disorder, can also predispose individuals to PCT. Twenty percent of individuals with PCT have an inherited form of the disease. Many individuals with the inherited form of PCT never develop symptoms.

If you or someone you know has porphyria, we recommend that you contact a genetics clinic to discuss this information with a genetics professional. To find a genetics clinic near you, contact your primary doctor for a referral.

What triggers a porphyria attack?

Porphyria can be triggered by drugs (barbiturates, tranquilizers, birth control pills, sedatives), chemicals, fasting, smoking, drinking alcohol, infections, emotional and physical stress, menstrual hormones, and exposure to the sun. Attacks of porphyria can develop over hours or days and last for days or weeks.

How is porphyria classified?

The porphyrias have several different classification systems. The most accurate classification is by the specific enzyme deficiency. Another classification system distinguishes porphyrias that cause neurologic symptoms (acute porphyrias) from those that cause photosensitivity (cutaneous porphyrias). A third classification system is based on whether the excess precursors originate primarily in the liver (hepatic porphyrias) or primarily in the bone marrow (erythropoietic porphyrias). Some porphyrias are classified as more than one of these categories.

What are the cutaneous porphyrias?

The cutaneous porphyrias affect the skin. People with cutaneous porphyria develop blisters, itching, and swelling of their skin when it is exposed to sunlight. The cutaneous porphyrias include the following types:

Also called congenital porphyria. This is a rare disorder that mainly affects the skin. It results from low levels of the enzyme responsible for the fourth step in heme production. It is inherited in an autosomal recessive pattern.

An uncommon disorder that mainly affects the skin. It results from reduced levels of the enzyme responsible for the eighth and final step in heme production. The inheritance of this condition is not fully understood. Most cases are probably inherited in an autosomal dominant pattern, however, it shows autosomal recessive inheritance in a small number of families.

A rare disorder that mainly affects the skin. It results from very low levels of the enzyme responsible for the fifth step in heme production. It is inherited in an autosomal recessive pattern.

A rare disorder that can have symptoms of acute porphyria and symptoms that affect the skin. It results from low levels of the enzyme responsible for the sixth step in heme production. It is inherited in an autosomal dominant pattern.

The most common type of porphyria. It occurs in an estimated 1 in 25,000 people, including both inherited and sporadic (noninherited) cases. An estimated 80 percent of porphyria cutanea tarda cases are sporadic. It results from low levels of the enzyme responsible for the fifth step in heme production. When this condition is inherited, it occurs in an autosomal dominant pattern.

A disorder that can have symptoms of acute porphyria and symptoms that affect the skin. It results from low levels of the enzyme responsible for the seventh step in heme production. It is inherited in an autosomal dominant pattern.

What are the acute porphyrias?

The acute porphyrias affect the nervous system. Symptoms of acute porphyria include pain in the chest, abdomen, limbs, or back; muscle numbness, tingling, paralysis, or cramping; vomiting; constipation; and personality changes or mental disorders. These symptoms appear intermittently. The acute porphyrias include the following types:

This is probably the most common porphyria with acute (severe but usually not long-lasting) symptoms. It results from low levels of the enzyme responsible for the third step in heme production. It is inherited in an autosomal dominant pattern.

A very rare disorder that results from low levels of the enzyme responsible for the second step in heme production. It is inherited in an autosomal recessive pattern.

Rickets causes soft, weak bones in children. It usually occurs when they do not get enough vitamin D, which helps growing bones absorb the minerals calcium and phosphorous. It can also happen when calcium or phosphorus levels are too low.

Your child might not get enough vitamin D if he or she

• Has dark skin
• Spends too little time outside
• Has on sunscreen all the time when out of doors
• Doesn't eat foods containing vitamin D because of lactose intolerance or a strict vegetarian diet
• Is breastfed without receiving vitamin D supplements
• Can't make or use vitamin D because of a medical disorder such as celiac disease

In addition to dietary rickets, children can get an inherited form of the disease. Symptoms include bone pain or tenderness, impaired growth, and deformities of the bones and teeth. Your child's doctor uses lab and imaging tests to make the diagnosis. Treatment is replacing the calcium, phosphorus, or vitamin D that are lacking in the diet. Rickets is rare in the United States.

Wilson disease is a rare inherited disorder that prevents your body from getting rid of extra copper. You need a small amount of copper from food to stay healthy. Too much copper is poisonous.

Normally, your liver releases extra copper into bile, a digestive fluid. With Wilson disease, the copper builds up in your liver, and it releases the copper directly into your bloodstream. This can cause damage to your brain, kidneys, and eyes.

Wilson disease is present at birth, but symptoms usually start between ages 5 and 35. It first attacks the liver, the central nervous system or both. The most characteristic sign is a rusty brown ring around the cornea of the eye. A physical exam and laboratory tests can diagnose it.

Treatment is with drugs to remove the extra copper from your body. You need to take medicine and follow a low-copper diet for the rest of your life. Don't eat shellfish or liver, as these foods may contain high levels of copper. At the beginning of treatment, you'll also need to avoid chocolate, mushrooms, and nuts. Have your drinking water checked for copper content and don't take multivitamins that contain copper.

With early detection and proper treatment, you can enjoy good health.