Metabolic disorders are illnesses that occur when the body is unable to process fats (lipids), proteins, sugars (carbohydrates), or nucleic acids properly. Most metabolic disorders are caused by genetic mutations that result in missing or dysfunctional enzymes that are needed for the cell to perform metabolic processes.
Most metabolic disorders are inherited, which means they are passed down through families. Examples of metabolic disorders include adrenoleukodystrophy (ALD), alkaptonuria, cystinosis, DIDMOAD syndrome (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness syndrome), glucose 6-phosphage dehydrogenase
(G6PD) deficiency, hyperornithinemia-hyperammonemia-homocitrullinuria (HHH), inborn errors of urea synthesis, Kearns-Sayre, maple syrup urine disease, McArdle's disease, MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes) syndrome, metabolic syndrome, phenylketonuria (PKU), pyruvate carboxylase deficiency, subacute necrotizing encephalopathy, Tay-Sachs disease, and trimethylaminuria.
Prognosis and treatment varies, depending on the type and severity of the disorder.
Adrenoleukodystrophy, ALD, alkaptonuria, biotin-responsive inborn errors of metabolism, coronary artery disease, cystinosis, DIDMOAD syndrome, Folling's disease, G6PD deficiency, GAMT deficiency, hyperalaninemia, hyperornithinemia, Kearns-Sayre syndrome, Leigh's disease, maple syrup urine disease, McArdle's disease, MELAS syndrome, metabolic syndrome, ornithine, PDH, phenylketonuria, PKU, pyruvate carboxylase deficiency, pyruvate dehydrogenase deficiency, subacute necrotizing encephalopathy, Tay-Sachs disease, trimethylaminuria, urea synthesis, wolfram syndrome.
Overview: Adrenoleukodystrophy is a rare and fatal genetic disorder that is passed down among families. Patients with ALD accumulate high levels of saturated, very long chain fatty acids (VLCFA) in the brain and adrenal cortex because they are unable to produce an enzyme that normally breaks down the fatty acids.
As a result, the condition leads to the breakdown of the myelin sheath, which is a fatty membrane that surrounds and protects the brain and spinal cord. It also causes the adrenal glands to become dysfunctional. The adrenal glands secrete cortisol, which regulates proper glucose metabolism, blood pressure, and insulin release for blood sugar maintenance. Cortisol is also involved in the inflammatory response.
Patients usually die within one to 10 years after symptoms appear.
Causes: ALD has two subtypes: X-linked ALD and neonatal ALD.
X-linked ALD occurs when the patient inherits the abnormal gene from one or both parents. Since males only have one X chromosome, they will have the disease if they inherit one copy of the mutated X chromosome. Since females have two X chromosomes, they must inherit two copies of the mutated chromosome in order to have the disease. If females have just one copy of the mutated gene, they are called carriers. Carriers of ALD may experience mild symptoms of ALD.
Neonatal ALD is also an inherited condition. Unlike X-linked ALD, the mutated gene that causes neonatal ALD is not located on the X-chromosome. This means that both male and female babies are affected equally.
Symptoms: Symptoms of X-linked ALD may develop in childhood or adulthood. The childhood form, which usually develops between the ages of four and 10, is the most severe. The most common symptoms are behavioral changes (such as abnormal withdrawal or aggression), poor memory, and poor performance at school. Other symptoms may include visual loss, learning disabilities, seizures, poorly articulated speech, difficulty swallowing, deafness, difficulty walking, poor coordination, fatigue, intermittent vomiting, darkening of the skin tone, and progressive dementia.
Symptoms of X-linked ALD are usually milder if they develop during adulthood. Adult-onset symptoms, which usually develop between the ages of 21 and 35, may include progressive stiffness, weakness or paralysis of the lower limbs, and loss of coordination. Although adult-onset ALD progresses more slowly than the childhood form, it may also result in deterioration of brain function.
Carriers of X-linked ALD may experience mild symptoms, which may include spastic weakness (but not paralysis of the legs called paraparesis), loss of coordination, excessive muscle tone, urinary problems, and numbness or tingling sensations in the hands or feet (called peripheral neuropathy).
Symptoms of neonatal ALD develop during infancy. Common symptoms include mental retardation, facial abnormalities, seizures, weak muscle tone, enlarged liver, and adrenal dysfunction. Symptoms of adrenal dysfunction typically includes muscle weakness and fatigue, weight loss and decreased appetite, darkening of the skin, low blood pressure, fainting, cravings for salt, low blood sugar levels, irritability, depression, diarrhea, nausea, and vomiting. This form usually progresses rapidly.
Diagnosis: If ALD is suspected, a blood test and/or skin biopsy will show that the patient has high levels of long chain fatty acids in the body. A magnetic resonance imaging (MRI) scan may also be performed to take pictures of the brain. If the patient has ALD, the MRI image will show damaged brain tissue, called white matter. A genetic test may also be performed to diagnosis neonatal ALD. During the procedure, a sample of the patient's blood is taken and sent to a laboratory. If abnormal chromosomes are found in the blood, the patient is diagnosed with the condition.
Treatment: There is currently no cure for ALD. Instead treatment focuses on reducing symptoms. Patients typically receive steroids to replace the hormones that are normally produced by the adrenal glands. Patients typically receive corticosteroids, such as hydrocortisone (Cortef® or Hydrocortone®), prednisone, cortisone, and dexamethasone (Decadron®, Baldex®, or Dexone®), to replace low levels of cortisol. These medications are taken once or twice a day to control hormone levels. Corticosteroids may increase blood glucose levels and should be used cautiously in diabetics.
Patients should also consume a diet that is low in long chain fatty acids. Patients should work with their healthcare providers and/or nutritionists to plan an appropriate diet.
Recent evidence suggests that a substance made of oleic acid and euric acid, called Lorenzo's oil" may help reduce or delay symptoms of X-linked ALD. However, Lorenzo's oil is not as effective as initially thought. Researchers are performing studies to determine if modifications to Lorenzo's oil can help make this treatment more effective.
Researchers are currently studying bone marrow transplantation as a possible treatment for patients with X-linked ALD.
Overview: Alkaptonuria, also called onchorosis, is a rare inherited metabolic disorder that is characterized by arthritis in adulthood and dark brown or black urine. This occurs when a patient unable to break down a type of amino acid called tyrosine due to a defect in an enzyme called homogentisic acid oxidase.
This genetic defect causes homogentisic acid to be excreted in the urine. The homogentisic acid turns brown when it is exposed to air. The bones and cartilage of the body may also be brown-colored.
Alkaptonuria is not life threatening. Patients typically require lifelong treatment to manage symptoms, but they are expected to live relatively normal, healthy lives.
Causes: Alkaptonuria is inherited as an autosomal recessive disorder. This means a patient must inherit two copies of the mutated gene (one from each parent) in order to develop the disorder. Autosomal genetic diseases do not involve the X or Y (sex) chromosome.
Patients who have only one copy of the gene are called carriers. Carriers do not have the disease, but they can pass a copy of the gene on to each of their children.
Symptoms: Infants, children, and adults with the disorder have dark brown or black urine. Adults may also experience progressive arthritis (especially of the spine), darkening of the color of the ears and nose, and dark spots on the white of the eyes and cornea.
Diagnosis: Alkaptonuria is diagnosed after a urine test (called a urinalysis). A sample of urine is taken from the patient. If there is a high level of homogentisic acid oxidase in the urine, alkaptonuria is diagnosed.
Treatment: Although there is no cure for the disorder, treatment can help reduce symptoms.
Some patients benefit from high-doses of vitamin C (ascorbic acid). The vitamin has been shown to reduce the build of brown pigment in the cartilage of the ears, which may slow the progression of arthritis.
Patients with arthritis may take nonsteroidal anti-inflammatory drugs (NSAIDs) to relieve pain and inflammation. Commonly used over-the-counter NSAIDs include ibuprofen (Advil® or Motrin®) and naproxen sodium (Aleve®). Higher doses of these drugs are also available by prescription. Commonly prescribed NSAIDs include diclofenac (Cataflam® or Voltaren®), nabumetone (Relafen®), and ketoprofen (Orudis®). NSAIDs may be taken by mouth, injected into a vein, or applied to the skin. Patients with more severe arthritis symptoms may benefit from the selective COX-2 inhibitor called celecoxib (Celebrex®). This medication is taken by mouth daily to reduce pain and inflammation associated with arthritis.
Overview: Cystinosis is characterized by an abnormal accumulation of an amino acid, called cystine, in the body. The condition causes cystine to build up in areas of the body, such as the kidneys, eyes, muscles, pancreas, and brain. This eventually leads to tissue and organ damage throughout the body. As the patient ages, different organs may become affected.
There are three types of cystinosis: infantile (nephropathic), late-onset, and benign. All three types are inherited, which means they are passed down among families.
When patients inherit the mutated gene, they are unable to transport cystine out of a cell compartment called the lysosome. Therefore, cystine builds up in the cell, forming crystals that ultimately destroy the cell.
Causes: All three types of cystinosis are inherited as autosomal recessive diseases. This means that patients must inherit two copies of the mutated gene (one from each parent) in order to develop the disease. Autosomal genetic disorders do not involve the X or Y (sex) chromosomes.
Patients who have one copy of the mutated gene will not have the disease. However, they may pass a copy of the mutated gene on to each of their children.
Symptoms: Symptoms of infantile cystinosis typically develop between the ages of six and 18 months old. Symptoms usually include excessive thirst and urination, rickets (bone disease caused by vitamin D deficiency), and failure to thrive. When children are about one year old the built up cystine in the eyes will look like crystals. These crystals are visible to the naked eye. Infantile cystinosis generally leads to sensitivity to light. Patients will also have high levels of cystine in their white blood cells. Over time, patients may develop problems such as underactive thyroid (called hypothyroidism), severe muscle weakness, and central nervous system complications. Without treatment, children with cystinosis develop end-stage kidney failure by the time they are nine years old. Kidney failure is fatal, unless the patient receives a kidney transplant.
Patients with adult-onset cystinosis experience symptoms similar to infantile cystinosis. The main difference is that adult-onset occurs later in life.
Benign cystinosis does not cause kidney damage. Instead patients typically develop crystals in their eyes, which may cause sensitivity to light during adulthood. Crystals also develop in the bone marrow and white blood cells, but they usually do not cause any symptoms.
Diagnosis: Infantile and adult-onset cystinosis is typically diagnosed after a blood test. Patients will have high levels of cystine in their white blood cells. Benign cystinosis is often discovered during a routine eye exam.
Pregnant women who are carriers of the disease may wish to have their fetus' undergo prenatal testing. Amniocentesis or chorionic villus sampling may be performed to retrieve a sample of the fetus' cells for genetic testing. During amniocentesis, a needle is inserted through the pregnant woman's abdominal wall and into the uterus. A small amount of fluid is removed from the sac surrounding the fetus. During chorionic villus sampling (CVS), a small piece of tissue, called chorionic villi, is removed from the placenta. The cells are then tested for mutated genes associated with cystinosis. If the mutated gene is present, the fetus has cystinosis. There are risks associated with both of these procedures, including miscarriage. Patients should discuss the potential risks and benefits of these procedures with their healthcare providers.
Treatment: Patients with cystinosis typically take a medication called cysteamine (Cystagon®) by mouth. This medication reduces the buildup of cystine in the cells. Therefore, it may help prevent organ damage, including kidney failure. Eye drops containing cysteamine may also be applied to the eyes.
Children with cystinosis usually need to drink fluids that contain sodium and potassium citrate to prevent dehydration.
Vitamin D and phosphate supplements may be necessary to prevent rickets. Patients should talk with their healthcare providers and nutritionists before taking supplements.
Patients who have underactive thyroids may need to take a man-made thyroid hormone called levothyroxine (Levothroid®, Levoxyl®, Synthroid®, or Unithroid®). This hormone is identical to the natural thyroid hormone called thyroxine. The medication is taken by mouth.
Patients with end-stage kidney failure need to receive a kidney transplant. If a patient receives a transplant, the new kidney will not be affected by the disease. This is because the donated organ does not contain the cystinosis genetic defect in its cells. As a result, the cells in the donated kidney cells are able to transport cystine from the lysosomes. However, a kidney transplant does not prevent the disease from spreading to other organs.
didmoad (wolfram) syndrome
Overview: DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness) syndrome, also called Wolfram syndrome, is an inherited neurodegenerative disease that is passed down among families.
The disorder occurs when a protein, called wolframin, does not function properly. It causes many abnormalities, including diabetes insipidus (the inability to concentrate the urine), diabetes mellitus (the inability to produce and/or properly use insulin), blindness (optic atrophy), and deafness. Patients also suffer from serious abnormalities of the nervous system.
Causes: DIDMOAD syndrome occurs in patients who have mutations in the gene that produces wolframin. As a result, wolframin does not function properly and symptoms of DIDMOAD develop. Patients can inherit different variations of the mutated gene. This means some patients may experience more severe symptoms than others.
The mutated gene is inherited as an autosomal recessive trait. This means patients must inherit two copies of the mutated gene (one from each parent) in order to inherit the disorder.
Symptoms: All patients with DIDMOAD syndrome develop type I diabetes between the ages of five and 15. Symptoms generally include increased thirst, increased urination, weight loss, decreased appetite, vomiting, nausea, abdominal pain, fatigue, and absence of menstruation (in females).
Some patients may develop diabetes insipidus, which causes them to urinate frequently and constantly feel thirsty.
All patients are colorblind. Overtime, vision gets progressively worse and leads to blindness by the time the patient is eight to 10 years old.
Some patients may experience hearing loss, which worsens over time and may lead to deafness.
Diagnosis: DIDMOAD is diagnosed after patients test positive for both type I diabetes and optic atrophy. Diabetes is diagnosed after the patient's blood sugar level is tested. Patients who have more than 200 milligrams of sugar per deciliter of blood and have symptoms of diabetes are diagnosed with the condition. Optic atrophy is diagnosed after an eye exam is performed.
Treatment: There is currently no cure for DIDMOAD syndrome. Patients receive insulin injections to manage type I diabetes. Initially, vision problems may be corrected with eyeglasses. However, the condition eventually progresses to permanent blindness that cannot be corrected. Patients with hearing loss may benefit from hearing aids.
glucose 6‑phosphate dehydrogenase (g6pd) deficiency
Overview: Glucose 6-phosphate dehydrogenase (G6PD) deficiency is an inherited enzyme deficiency of the red blood cells. Patients with the disorder have low levels of G6PD in their blood cells. This causes the red blood cells to die prematurely when the patient has an infection or is exposed to certain chemicals in foods or medications. When there are low levels of red blood cells in the blood, the condition is called causing hemolytic anemia.
Medications, such as antimalarial drugs, aspirin, nonsteroidal anti-inflammatory drugs (e.g. ibuprofen), quinidine, quinine, and sulfonamids, are the most common triggers of hemolytic anemia in patients with G6PD deficiency. Other chemicals, including those in mothballs, may also trigger symptoms in patients.
The severity of the illness varies among patients, depending on the magnitude of the missing enzyme.
In general, most episodes of hemolytic anemia resolve once the infection is treated or the food or medication is stopped. Rarely, kidney failure or death may occur after a severe hemolytic episode. Therefore, patients should seek immediate medical treatment if they experience signs and symptoms, such as rapid heartbeat and yellow eyes or skin (jaundice).
The disorder primarily affects males because it is inherited as an X-linked recessive trait.
Causes: A patient develops G6PD deficiency when he/she inherits a mutated chromosome from one or both parents. Since males only have one X chromosome, they will have the disease if they inherit one copy of the mutated X chromosome. Since females have two X chromosomes, they must inherit two copies of the mutated chromosome in order to have the disease. If females have just one copy of the mutated gene, they are called carriers. Carriers do not have the disease, but they may pass the mutated gene on to each of their children.
Symptoms: Patients with G6PD deficiency are not normally anemic. They do not experience any signs or symptoms of the disease until they have an infection or are exposed to certain chemicals in food or medication.
Symptoms of hemolytic anemia may include dark urine, enlarged spleen, fatigue, pale complexion, rapid heartbeat, shortness of breath, and yellow skin or eyes (jaundice). Episodes of hemolytic anemia are usually short because young red blood cells have normal G6PD activity.
Diagnosis: A blood test is the standard diagnostic test for G6PD deficiency. Patients with the disorder will have low levels of G6PD in their blood in between episodes.
Patients may also be diagnosed during an episode of hemolytic anemia. During an attack, patients will have high levels of bilirubin in their blood. When red blood cells die, bilirubin is released into the bloodstream. If high levels of bilirubin are detected, the patient's G6PD levels may be measured after the attack to confirm a diagnosis.
Treatment: There is currently no cure for G6PD deficiency. Treatment focuses on stopping the cause of the episode. In rare cases, a blood transfusion may be necessary. If an infection is causing an episode, the infection should be treated as quickly as possible. If a chemical or food is causing the reaction, it should be discontinued and symptoms will eventually resolve. If a medication is causing the reaction, patients should stop taking the drug after consulting their healthcare providers.
Patients can prevent episodes of hemolytic anemia by avoiding medications and foods known to trigger reactions. Patients should talk to their healthcare providers to determine what medications and foods are safe. Maintaining good hygiene and minimizing contact with sick individuals helps reduce the risk of acquiring infections that may lead to hemolytic episodes.
Overview: Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) is a rare inherited metabolic disorder that is characterized by learning disabilities and poor coordination. HHH occurs when an amino acid, called ornithine, builds up in the blood and prevents nitrogen waste from being removed from the body. Abnormally high levels of nitrogen in the body can lead to cognitive dysfunction. An estimated 50 cases of HHH have been reported to date worldwide.
Prognosis varies significantly among patients. Some patients are able to live relatively normal lives while others may experience progressive neurological and cognitive dysfunction.
Causes: HHH is inherited as an autosomal recessive trait. This means patients must inherit two copies of the mutated gene (one from each parent) in order to develop the disorder. Patients are called carriers if they have one copy of the gene and do not experience symptoms. Although carriers do not have the disease, they can pass their copy of the mutated gene on to each of their children.
Symptoms: The severity and variation of symptoms vary widely. Symptoms may become apparent during infancy or adulthood. Growth and developmental delays, learning disabilities (especially speech delay), and periodic confusion and loss of coordination (called ataxia) are typical symptoms of HHH. Early detection and treatment may lead to a more favorable outcome.
Diagnosis: Patients with HHH will have high levels of ornithine and nitrogen in their blood and urine.
Treatment: Patients may receive supplementation with arginine to reduce nitrogen levels in the blood. Other medications, such as sodium benzoate/sodium phenylacetate (Ammonul® or Ucephan®), may be taken to reduce nitrogen levels.
Patients must follow a low-protein diet to help reduce signs and symptoms of the disorder.
inborn errors of urea synthesis
Overview: Inborn disorders of urea synthesis occur when the urea cycle is disrupted. The urea cycle is a series of enzyme reactions that remove nitrogen waste from the blood. When the urea cycle functions normally, excess nitrogen is then excreted in the urine.
Patients with inborn errors of urea synthesis have increased levels of ammonia, a substance that contains nitrogen, in the blood. This condition, which is called hyperammonemia, leads to mental retardation and eventually coma and death.
Causes: Inborn errors of urea synthesis are inherited, which means they are passed down from parents to their children. Most urea cycle disorders are inherited as autosomal recessive traits. This means a child must inherit two copies of the mutated gene (one from each parent) in order to develop the disease.
Symptoms: Depending on the specific disorder, patients may develop symptoms during infancy or adulthood. Most patients with inborn errors of urea synthesis suffer from severe mental impairment. Symptoms may include loss of coordination, seizures or tremors, lethargy, muscle stiffness or weakness, and increased heartbeat. Even with treatment, the condition eventually progresses to coma and death.
Diagnosis: Patients are diagnosed with inborn errors of urea synthesis if they have high levels of nitrogen in their blood. Healthy individuals typically have 7-20 milligrams of nitrogen per deciliter of blood. Patients with higher levels are positively diagnosed.
Treatment: There is currently no cure for inborn errors of urea synthesis. Patients typically receive medications, such as sodium phenylacetate/sodium benzoate (Ammonul®), which help remove nitrogen waste from the body.
Patients with these disorders must consume diets that are low in dietary protein. This is because dietary protein is a major source of nitrogen, and it may worsen symptoms.
Overview: Kearns-Sayre syndrome is a rare neuromuscular disorder that primarily affects the eyes. The condition occurs when patients have mutated mitochondria inside their cells. In healthy individuals, the mitochondria supply the cell with energy so it can perform normal functions. When the mitochondria do not function properly, the cells do not receive enough energy.
Causes: Although individuals with Kearns-Sayre syndrome are born with the disorder, it does not appear to be inherited. Instead, researchers believe that patients are randomly born with a genetic defect that causes the disorder.
Symptoms: Symptoms of Kearns-Sayre syndrome develop before the age of 20. The muscles that control eye movement start to become paralyzed. This paralysis worsens over time. The retina, part of the eye that is responsible for sight, starts to deteriorate. As a result, patients suffer from progressive vision loss that leads to blindness.
In addition to the eyes, symptoms may develop in many different organs throughout the body, including the brain and heart. Other symptoms may include difficulty walking or moving, muscle weakness, dementia, brain damage, deafness, heart disease, short stature, and small sex organs.
Diagnosis: Kearns-Sayre syndrome can be diagnosed after a spinal tap. During the procedure, a needle is inserted into the patient's lower back and a sample of fluid is taken from the spinal cord. If the patient has the disorder, elevated levels of lactate will be present in the cerebrospinal fluid.
A muscle biopsy may also be performed to diagnose Kearns-Sayre syndrome. During the procedure, the patient receives an injection of anesthetic to numb the area. Then a small sample of muscle tissue is removed with a needle or a scalpel. The muscle is analyzed for abnormal mitochondria. If the patient has abnormal mitochondria in the muscle cells, a positive diagnosis is made.
Treatment: There is currently no cure for Kearns-Sayre syndrome. Even with treatment to reduce symptoms, the disorder generally worsens over time. Patients typically receive physical therapy to help maintain or increase muscle strength. Some patients typically take ubidecarenone (Coenzyme Q10, Ubiquinone®) by mouth to support normal heart function. Patients should regularly visit their eye doctors and heart doctors (cardiologists) to monitor their conditions.
maple syrup urine disease (msud)
Overview: Maple syrup urine disease (MSUD) is an inherited metabolic disorder that is caused by an enzyme deficiency. Patients have low levels of an enzyme called branched-chain alpha-keto acid dehydrogenase (BCKD) in the blood. This enzyme is needed to break down certain parts of proteins, called amino acids. They break down the amino acids: leucine, isoleucine, and valine. Without the BCKD enzyme, these amino acids build up to toxic levels in the body. If left untreated, MSUD will cause brain damage and progressive nervous system damage.
MSUD is a genetic disorder, which means it is passed down from parents to their children. MSUD is inherited as an autosomal recessive trait. This means a child must inherit two copies of the mutated gene (one from each parent) in order to develop the disease.
Symptoms: Symptoms include urine that smells like maple syrup, difficulty feeding, lethargy, seizures, vomiting, muscle spasm, seizures, and coma.
Diagnosis: MSUD is diagnosed after a urine or blood test. Patients with MSUD will have high levels of amino acids and low levels of BCKD in their blood and urine.
Treatment: Without treatment, MSUD can be life threatening. With early diagnosis and prompt treatment, many patients are able to live long and relatively healthy lives.
Infants with MSUD must receive an infant formula that contains low levels of the amino acids leucine, isoleucine, and valine. Patients must then continue a diet that does not contain these amino acids for the rest of their lives. Several commercially available formulas, such as MSUD Express®, are specifically designed for MSUD patients. These formulas are protein supplements that do not contain branched-chain amino acids. This helps prevent brain damage. Patients should also visit their healthcare providers regularly to monitor their conditions.
Overview: MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes) syndrome is a rare type of dementia.
Patients with MELAS are born with mutations in the genetic material (DNA) inside the mitochondria of their cells. The mitochondria produce the energy that cells need to perform everyday functions. Most of the DNA inside of the mitochondria is used to produce proteins, which helps power the cells in the body.
There is currently no cure for MELAS syndrome. The disease is fatal.
Causes: The cause of MELAS is not fully understood. Researchers believe that genetics may play a role because it appears to run in some families.
Symptoms: Symptoms of MELAS can develop at different times in life, ranging from age four to 40 or older. Most patients develop symptoms before the age of 20. The mutated mitochondria lead to brain dysfunction (encephalopathy), which causes abnormal thinking (dementia), seizures, and headaches. Patients also suffer from muscle disease that causes lactic acid to build up in the blood (lactic acidosis). Patients also develop temporary paralysis (stroke-like episodes).
Diagnosis: A muscle biopsy is the standard diagnostic test for MELAS. A small sample of the patient's muscle tissue is removed with a needle or a scalpel. The patient will not feel much pain, if any, because an anesthetic is injected to numb the area. The tissue sample is then analyzed in a laboratory. Patients with MELAS will have ragged red fibers in their muscles.
Treatment: There is currently no cure for MELAS syndrome. Several antioxidants, vitamins, and supplements, including coenzyme Q10, menadione (vitamin K3), and riboflavin, have been suggested as possible treatments to manage symptoms. However, they have been used with varying success.
Overview: Metabolic syndrome, also called syndrome X, is a group of conditions, including high blood pressure, high insulin levels, excess fat around the waist, and high cholesterol, that occur at the same time. Patients with three of more of these conditions have metabolic syndrome. Patients with metabolic syndrome have an increased risk of developing heart disease, stroke, and diabetes.
Causes: Most experts believe that metabolic syndrome is caused by a condition called insulin resistance. This occurs when the body does not respond appropriately to insulin. This hormone is normally produced by the pancreas to control the amount of sugar in the bloodstream. Patients with insulin resistance have high levels of insulin and sugar in the blood.
Insulin resistance interferes with many biological processes. A high level of insulin increases the amount of fat in the blood and disrupts kidney function, which leads to high blood pressure.
Many factors increase a patient's risk of developing metabolic syndrome, including obesity, age, diabetes, heart disease, and polycystic ovary syndrome.
Symptoms: Patients with metabolic syndrome are typically overweight or obese. They tend to have excess fat around the waist. Symptoms of insulin resistance are not always apparent. Having too much insulin in the blood may cause patches of skin on the neck, elbows, knees, knuckles, and/or under the arms to become dark in color. High blood pressure and high cholesterol do not usually cause any symptoms.
Diagnosis: Patients are diagnosed with metabolic syndrome if they have at least three out of the four conditions associated with the syndrome: 1) patients have an elevated waist circumference that is greater than 35 inches in women and 40 inches in men; 2) patients have 150 milligrams or more of triglycerides per deciliter of blood and have low levels of HDL in their blood (less than 40 milligrams of HDL per deciliter of blood in men and less than 50 milligrams of HDL per deciliter of blood in women are considered low levels); and 3) patients have high blood pressure. 4) Patients with more than 100 milligrams of sugar per deciliter of blood.
Treatment: Patients may receive cholesterol-lowering drugs and anti-hypertensive drugs to lower blood pressure. Medications, called insulin sensitizers, may help the body make proper use of insulin. Some healthcare providers may recommend a daily dose of aspirin to reduce the risk of heart attack or stroke. Patients should only take aspirin regularly after talking with their healthcare providers.
Patients with metabolic syndrome are encouraged to make lifestyle changes in order to improve their conditions and prevent heart disease. Individuals should focus on exercising more and eating healthfully. Most experts recommend 30-60 minutes of moderate exercise on most days of the week.
Patients who lose as little as 5-10% of their bodyweight can reduce their blood sugar levels and risk of developing diabetes. Weight loss also reduces high blood pressure.
Patients should visit their healthcare providers regularly to monitor their conditions.
Overview: Phenylketonuria (PKU), also called Folling's disease, is an inherited disorder that occurs when patients are missing an enzyme that is needed to process a protein called phenylalanine. As a result, phenylalanine builds up in the body. Without proper treatment, the condition can be fatal.
Patients with PKU must follow a diet that does not contain any phenylalanine. Phenylalanine is present in high-protein foods, such as cheese, milk, nuts, or meats.
Causes: PKU is inherited as an autosomal recessive trait. Patients develop PKU when they inherited one mutated gene from each of their parents. Patients must inherit two copies of the gene (one copy from each parent) in order to develop the disorder. Patients are called carriers if they have only one copy of the gene and do not experience symptoms. Although carriers do not have PKU, they can pass their copy of the mutated gene on to their children.
Symptoms: Newborns with PKU do not experience any symptoms. However, if the infant does not receive treatment, he/she will develop symptoms within a few months. Symptoms vary from mild to severe. Common symptoms include mental retardation, seizures, tremors, behavioral or social problems, skin rashes, hyperactivities, vomiting, and breath that smells musty. Children will have fair skin and blue eyes because phenylalanine cannot be converted into melanin, which is responsible for the pigment of hair and skin.
The most severe form of the disorder is known as classic PKU. Children with untreated classic PKU usually develop permanent mental retardation and behavioral problems by the time they are one year old.
Less severe forms of PKU, sometimes called mild or moderate PKU, have a smaller risk of brain damage. However, most patients with these forms of the disorder still require a special diet to prevent mental retardation and other complications.
Diagnosis: All newborns in the United States are screened for PKU. Many other countries, including Canada, also screen newborns for PKU. The test is performed one or two days after birth. A small sample of blood is taken from the infant's heel. Tests are most accurate when they are performed between 24 hours and seven days after birth.
Pregnant mothers may have their fetus' screened for PKU if they have a family history of the disorder. Amniocentesis or chorionic villus sampling may be performed to retrieve a sample of the fetus' cells for genetic testing. During amniocentesis, a needle is inserted through the pregnant woman's abdominal wall and into the uterus. A small amount of fluid is removed from the sac surrounding the fetus. During chorionic villus sampling (CVS), a small piece of tissue, called chorionic villi, is removed from the placenta. The cells are then tested for mutated genes associated with cystinosis. If the mutated gene is present, the fetus has the disorder. There are risks associated with these both of these procedures, including miscarriage. Patients should discuss the potential risks and benefits of these procedures with their healthcare providers.
Treatment: Newborns with PKU will have to be fed with a special formula that does not contain any phenylalanine.
Patients will need to continue a strict diet with limited amounts of phenylalanine, which is primarily found in foods that are high in protein. This means patients should avoid foods such as milk and dairy products, eggs, nuts, beans, meats, and fish. This restrictive diet has been shown to effectively eliminate symptoms of PKU. Since the severity of the disorder varies among patients, healthcare providers will recommend specific diets for each individual patient. Patients should visit their healthcare providers regularly to monitor their conditions.
pyruvate carboxylase deficiency (hyperalaninemia)
Overview: Pyruvate carboxylase deficiency, also called hyperalaninemia, is an inherited disorder that occurs when patients are born with low levels of an enzyme called pyruvate carboxylase. This enzyme is needed to break down alanine in the blood.
As a result, patients with hyperalaninemia accumulate high levels of lactic acid in the blood. Because hyperalaninemia is a progressive disorder, patients typically die before the age of six months.
Causes: Hyperalaninemia is an inherited as an autosomal recessive disorder that is passed from parents to their children. Patients develop the disorder when they inherit one mutated gene from each of their parents.
Symptoms: Symptoms may include delayed development, muscle weakness, poor motor control, seizures, and vomiting.
Diagnosis: A blood test is the standard diagnostic test for hyperalaninemia. Patients with the disorder will have high levels of lactic acid in the blood.
Treatment: There is currently no cure for hyperalaninemia. Patients may receive thiamin (vitamin B1) to reduce the buildup of lactic acid in the blood. However, this treatment has a minimal effect on the patient's prognosis.
subacute necrotizing encephalopathy
Overview: Subacute necrotizing encephalopathy, also called Leigh's disease, is an inherited disorder that is characterized by the degeneration of the brain and spinal cord (central nervous system).
Patients with Leigh's disease are missing an enzyme called pyruvate dehydrogenase.
Patients typically only live to be six or seven years old. A few patients have lived until their teenage years.
Causes: Patients may inherit the disorder as an autosomal recessive trait. This means that patients must inherit two copies (one from each parent) of the mutated gene in order to develop the disease. Patients are called carriers if they inherit only one copy of the mutated gene and do not experience symptoms. Although carriers do not have the disorder, they can pass their copy of the mutated gene onto each of their children.
Patients may also inherit the disorder as an X-linked recessive trait. This occurs when the patient inherits the abnormal gene from one or both parents. Since males only have on X chromosome, they will have the disease if they inherit one copy of the mutated X chromosome. Since females have two X chromosomes, they must inherit two copies of the mutated chromosome in order to have the disease. If females have just one copy of the mutated gene, they are called carriers. Although carriers do not have the disease, they may pass their copy of the mutated gene on to each of their children.
Symptoms: Symptoms typically develop when the patient is between the ages of three months and two years. Symptoms worsen over time. Common symptoms include loss of previously acquired motor skills, decreased appetite, vomiting, seizure, irritability, generalized weakness, lack of muscle tone, and episodes of lactic acidosis.
Diagnosis: Imaging studies, such as a computerized tomography (CT) scan or magnetic resonance imaging (MRI) scan, may be performed to confirm a diagnosis. These tests provide images of the brain. Patients with the disorder will show changes in the brain that occur when nerve cells die.
A DNA analysis may also be performed to confirm a diagnosis. A small sample of the patient's blood is sent to a laboratory for testing. If genetic mutations associated with the disorder are present, a positive diagnosis is made.
Treatment: The most common treatment for Leigh's disease is thiamin, also called vitamin B1. A high-fat, low carbohydrate diet may also be recommended. Medication called sodium bicarbonate or sodium citrate may also be prescribed to manage lactic acidosis. However, despite these treatments, the prognosis for patients with Leigh's disease is poor.
tay‑sachs disease (tsd)
Overview: Tay-Sachs disease (TSD) is an inherited disorder that progressively destroys the brain and nervous system. Overtime, the body starts to lose basic functioning leading to deafness, blindness, paralysis, and eventually death.
The most common form develops when the infant is six months old. These patients typically die within a few years.
Juvenile onset typically develops during childhood. These patients typically die between the ages of 10 to 15.
Late-onset TSD may develop when the patient is an adolescent or adult. These patients have normal life expectancies.
Causes: TSD is passed on from parents to their children. Patients inherit a mutated gene that causes a deficiency of an enzyme called hexoaminidase (hex-A). The body needs this enzyme to break down a fat called GMT2 ganglioside. As a result, this lipid accumulates in the brain and other tissues of patients with TSD. This leads to the deterioration of the brain and nervous system.
Symptoms: Symptoms of early-onset TSD may include decreased eye contact, twitchy eyes, and difficulty focusing on objects. Over the next several months, symptoms may include limp and floppy muscles, decreased alertness, decreased playfulness, difficulty sitting up, poor motor skills, decreased hearing and eventual deafness, gradual loss of vision, and an abnormally large head (macrocephaly). During the last stage of the disease, the child typically becomes blind, mentally retarded, paralyzed, and unresponsive. The patient may have difficulty swallowing or breathing and may have seizures.
Symptoms of juvenile-onset TSD are generally similar to early-onset TSD. However, symptoms of juvenile-onset TSD do not develop until the patient is three to 10 years old.
Symptoms of late-onset TSD may develop when the patient is an adolescent on in his/her mid 30s. Common symptoms include personality changes, muscle weakness or twitching, slurred speech, impaired thinking, poor memory, difficulty with comprehension, short attention span, and difficulty distinguishing between what is real and unreal (psychosis).
Diagnosis: TSD is diagnosed after low levels of hex-A are found in the blood or other body tissues. An eye exam may also show a cherry-red spot in the center of the retina, which is characteristic of the disease.
Treatment: There is currently no cure for TSD. Treatment focuses on making the patient as comfortable as possible.
Overview: Trimethylaminuria is an inherited metabolic disorder that is characterized by offensive body odor that smells like rotting fish due to the excessive excretion of a protein called trimethylamine (TMA) in urine, sweat, and breath.
Causes: Trimethylaminuria is inherited, which means it is passed from parents to their children. Patients with trimethylaminuria are missing an enzyme that is needed to break down TMA. As a result, TMA builds up in the body and symptoms of trimethylaminuria develop.
Symptoms: Common symptoms include offensive body odor, increased heartbeat, and high blood pressure.
Diagnosis: A blood test is considered the standard diagnostic test for trimethylaminuria. Patients who have high levels of TMA in their blood are diagnosed with the disorder.
Treatment: Patients are able to live normal, healthy lives by eating a diet that is very limited in trimethylamine. Patients should avoid or minimize foods, such as eggs, legumes, certain meats, fish, and foods that contain choline, nitrogen, and sulfur. Patients should talk with their healthcare providers and/or nutritionists to design a safe and healthy diet.