Single Gene Disorders

These disorders involve mutations in the DNA sequences of single genes. As a result, the protein the gene codes for is either altered or missing.

Adenosine deaminase (ADA) deficiency

What is Adenosine deaminase (ADA) deficiency?

The disease is caused by a mutation in a gene on chromosome 20. The gene codes for the enzyme adenosine deaminase (ADA). Without this enzyme, the body is unable to break down a toxic substance called deoxyadenosine. The toxin builds up and destroys infection-fighting immune cells called T and B lymphocytes.

ADA deficiency is one form of SCID (severe combined immunodeficiency), a disorder that affects the immune system. ADA deficiency is very rare, but very dangerous, because a malfunctioning immune system leaves the body open to infection from bacteria and viruses.

How do people get ADA deficiency?

ADA deficiency is an autosomal recessive disorder. Both parents need to pass a copy of the defective gene to their child in order for that child to inherit the deficiency.

What are the symptoms of ADA deficiency?

Because ADA deficiency affects the immune system, people who have the disorder are more susceptible to all kinds of infections, particularly those of the skin, respiratory system, and gastrointestinal tract. They may also be shorter than normal. Sadly, most babies who are born with the disorder die within a few months.

How do doctors diagnose ADA deficiency?

Doctors can identify ADA deficiency during the mother's pregnancy (1) by taking a tiny sample of tissue from the amniotic sac where the baby develops (called chorionic villus sampling), or (2) by looking at enzyme levels in a fetal blood sample taken from the umbilical cord. After the child is born, doctors can test a sample of his or her blood to see if it contains ADA.

How is ADA deficiency treated?

There are no real cures for ADA deficiency, but doctors have tried to restore ADA levels and improve immune system function with a variety of treatments:

  • Bone marrow transplantation from a biological match (for example, a sibling) to provide healthy immune cells
  • Transfusions of red blood cells (containing high levels of ADA) from a healthy donor
  • Enzyme replacement therapy, involving repeated injections of the ADA enzyme
  • Gene therapy - to insert synthetic DNA containing a normal ADA gene into immune cells

Alpha-1 Antitrypsin Deficiency

What is alpha-1 antitrypsin deficiency (Alpha-1)?

When SERPINA1 is mutated, the abnormal alpha-1 antitrypsin protein gets stuck in the liver and is unable to pass into the bloodstream. Without protection from this protein, the lungs are left vulnerable to attack by neutrophil elastase. The accumulation of alpha-1 antitrypsin can also damage the liver.

Alpha-1 antitrypsin deficiency (also referred to as Alpha-1) is caused by mutations in the SERPINA1 gene on chromosome 14. This gene codes for an enzyme called alpha-1 antitrypsin. It is made in the liver and released into the blood, ultimately to protect the lungs from attack by an enzyme called neutrophil elastase. Neutrophil elastase is made by white blood cells in response to infection or irritants, to digest damaged tissue in the lungs.

How do people get Alpha-1?

Alpha-1 is an autosomal recessive disorder. A child must inherit one abnormal gene from each parent to develop the disease. If a child inherits a normal gene from one parent and an abnormal gene from the other, he or she will only be a carrier. Carriers produce lower-than-normal levels of the alpha-1 antitrypsin protein, but they still have enough of it to protect their lungs.

Autosomal Recessive

What are the symptoms of Alpha-1?

Alpha-1 antitrypsin deficiency damages the tiny air sacs (alveoli) in the lungs. When the alveoli are damaged, the lungs aren't able to expand and contract well enough for the person to breathe normally. Patients may feel short of breath, and they may cough or wheeze. As the lungs deteriorate, many patients develop lung diseases, such as emphysema, asthma, or chronic bronchitis.

About 10% of infants and 15% of adults with the disorder also have liver damage, which can develop into the chronic disease cirrhosis. In rare cases, patients may develop hard and painful lumps under their skin, called panniculitis.

How do doctors diagnose Alpha-1?

Alpha-1 antitrypsin deficiency is often misdiagnosed because its symptoms look a lot like the symptoms of asthma, bronchitis, or smoking-induced emphysema. Doctors can test for the disorder by checking a sample of the patient's blood for abnormal alpha-1 antitrypsin levels. To measure lung and liver function, doctors may also do chest x-rays, pulmonary (lung) function tests, lung volume measurements, and blood tests to check liver function.


How is Alpha-1 treated?

Doctors try to increase the amount of alpha-1 antitrypsin in a patient's blood with augmentation therapy. Each week, the patient is given injections of alpha-1 antitrypsin from the blood of healthy donors. Although augmentation therapy does not cure alpha-1-antitrypsin deficiency, it can slow its progression.

Researchers are currently experimenting with gene therapy, in which the patient is given the healthy gene using a modified virus. Unlike the viruses that make us sick, this special virus 'infects' the patient's cells and causes them to start making the normal protein.

To control bronchial symptoms, doctors prescribe asthma medications, such as inhaled steroids or bronchodilators. Patients in the late stages of the disease may have so much lung or liver damage that they need an organ transplant.

Interesting facts about Alpha-1

Alpha-1 is more prevalent among caucasians, affecting 1 in 2,500. In fact, it is one of the most common autosomal recessive disorders among this population. This disorder is hard to spot because people are often not diagnosed until middle adulthood. An estimated 95% of people who have alpha-1 antitrypsin deficiency have never been diagnosed.

Patients with this disorder need to stay away from tobacco, because smoking worsens the disease. Smoke damages the lungs by increasing secretion of neutrophil elastase and by inhibiting alpha-1 antitrypsin.

More information

Alpha-1 Association
The Alpha-1 Association Genetic Counseling Center provides confidential genetic counseling to the Alpha-1 community. It is also an expert resource for health care professionals. The toll-free phone number is 1-800-785-3177.
American Lung Association
American Liver Foundation

Cystic Fibrosis

What is cystic fibrosis?

Cystic Fibrosis Chromosome

Cystic fibrosis is a genetic disorder that affects the respiratory and digestive systems.

People with cystic fibrosis inherit a defective gene on chromosome 7 called CFTR (cystic fibrosis transmembrane conductance regulator). The protein produced by this gene normally helps salt (sodium chloride) move in and out of cells. If the protein doesn't work correctly, that movement is blocked and an abnormally thick sticky mucus is produced on the outside of the cell. The cells most seriously affected by this are the lung cells. This mucus clogs the airways in the lungs, and increases the risk of infection by bacteria.

The thick mucus also blocks ducts in the pancreas, so digestive enzymes can't get into the intestines. Without these enzymes, the intestines cannot properly digest food. People who have the disorder often do not get the nutrition they need to grow normally.

Finally, cystic fibrosis affects the sweat glands. Too much salt is lost through sweat, which can disrupt the delicate balance of minerals in the body.

How do people get cystic fibrosis?

Cystic fibrosis is a recessive disorder, which means that both parents must pass on the defective gene for any of their children to get the disease. If a child inherits only one copy of the faulty gene, he or she will be a carrier. Carriers don't actually have the disease, but they can pass it on to their children.

What are the symptoms of cystic fibrosis?

Symptoms of cystic fibrosis can include coughing or wheezing, respiratory illnesses (such as pneumonia or bronchitis), low weight, salty-tasting skin, and greasy stools. Because the lungs are clogged and repeatedly infected, lung cells don't last as long as they should. Therefore, cystic fibrosis patients who don't receive treatment have shortened lifespans.

Autosomal Recessive

How do doctors diagnose cystic fibrosis?

People with cystic fibrosis have between 2 and 5 times the normal amount of salt in their sweat. Thus, doctors can use a sweat test to measure the amount of salt (sodium chloride) in a person's sweat. Sweat is collected from the person's arm or leg and taken to a laboratory to be analyzed.

In newborns, doctors can measure the amount of a protein called trypsinogen in the blood. The level of this protein is higher than normal in people with cystic fibrosis.

Finally, genetic tests can identify a faulty CFTR gene using a sample of the patient's blood.

CF Channel

How is cystic fibrosis treated?

Although there is no cure for cystic fibrosis, new treatments are helping people with the disease live longer than before. Most treatments work by clearing mucus from the lungs and preventing lung infections. Common treatments include:

  • Chest physical therapy, in which the patient is repeatedly clapped on the back to free up mucus in the chest
  • Inhaled antibiotics to kill the bacteria that cause lung infections
  • Bronchodilators (also used by people with asthma) that help keep the airways open
  • Pancreatic enzyme replacement therapy to allow proper food digestion
  • Gene therapy (a treatment currently in clinical trials), in which the healthy CFTR gene is inserted into the lung cells of a patient to correct the defective gene
CF Organs
Organs Affected By Cystic Fibrosis

Interesting facts about cystic fibrosis

More than 1,000 different mutations in the CFTR gene have been identified in cystic fibrosis patients. The most common mutation (in 70% of cystic fibrosis patients) is a three-base deletion in the DNA sequence, causing an absence of a single amino acid in the protein product.

Some evidence suggests that cystic fibrosis carriers are resistant to certain types of bacterial infections

About 2,500 babies are born with cystic fibrosis in the U.S. each year.

More than 10 million Americans carry the cystic fibrosis gene but don't know it.


What is galactosemia?

Galactosemia Chromosome Galactosemia is a rare disorder that affects the body's ability to break down a food sugar called galactose (found in milk and other dairy products).

The body breaks down lactose into galactose and glucose and uses these sugars for energy. Most people with galactosemia are missing an enzyme (called GALT) that helps further break down galactose. Defects in galactose metabolism cause toxic chemicals to build up in cells of the body.

How do people get galactosemia?

The most common form of the disorder, classic galactosemia, is passed down in an autosomal recessive pattern. To get the disorder, a child must inherit one defective copy of the gene from each parent. Inheriting one normal gene and one mutated gene makes a person a carrier. A carrier produces less of the GALT enzyme than normal, but is still able to break down galactose and avoid having symptoms of galactosemia. However, carriers can pass the mutated gene to their children.

What are the symptoms of galactosemia?

Defects in galactose metabolism can cause several severe symptoms, including kidney failure, an enlarged liver, cataracts (clouding of the eye lens), poor growth, and intellectual disability.

People can inherit a milder form of the disorder when a different gene, also involved in galactose metabolism, is mutated. These patients often suffer from cataracts, but not the other symptoms associated with classical galactosemia.

Autosomal Recessive

Galactosemia Pathway

How do doctors diagnose galactosemia?

In most states, babies are tested for galactosemia at birth. Using a tiny blood sample taken from the baby's heel, the test checks for low levels of the GALT enzyme. This allows for prompt treatment, which can substantially prevent the serious symptoms of this disorder.

For those families with a history of the disorder, a doctor can determine during a woman's pregnancy whether her baby has galactosemia (1) by taking a sample of fluid from around the fetus (amniocentesis), or (2) by taking a sample of fetal cells from the placenta (chorionic villus sampling or CVS).

How is galactosemia treated?

The only way to treat galactosemia is through dietary restrictions. People with the disorder must stay away from foods and drinks containing galactose, including milk, cheese, and legumes (dried beans).

Huntington's Disease

What is Huntington's Disease?

Huntington's Disease Chromosome Huntington's Disease (HD) is a brain disorder that affects a person's ability to think, talk, and move.

The disease destroys cells in the basal ganglia, the part of the brain that controls movement, emotion, and cognitive ability. HD is caused by a mutation in a gene on chromosome 4. The job of its protein product, huntingtin, is to direct the delivery of small packages (vesicles containing important molecules) to the outside of the cell. Normally, the coding region of this gene contains the DNA sequence "CAG" repeated again and again. The number of times this triplet is repeated varies from person to person, ranging from 10 to 26 times. People with HD have an abnormally high number of these CAG triplets, approximately 40 or more. This likely disrupts the function of the gene's protein product, but how the expansion of the CAG repeat causes disease is unknown. Somehow the brain cells of HD patients accumulate clumps of protein that become toxic, resulting in cell death. Some patients lose more than 25% of their brain cells before they die.

How do people get Huntington's Disease?

Huntington's disease is inherited in an autosomal dominant pattern. This means that everyone who inherits the faulty gene will eventually get the disease. A parent with a mutation in the HD gene has a 50 percent chance of passing the disease to their children.

Autosomal Dominant

What are the symptoms of Huntington's Disease?

Huntington's disease affects the part of the brain that controls thinking, emotion, and movement. Most people who have the disease start to see symptoms between the ages of 30 and 50 (but symptoms can appear earlier or later in life). The disease gets worse over time.

Symptoms include poor memory, depression and/or mood swings, lack of coordination, twitching or other uncontrolled movements, and difficulty walking, speaking, and/or swallowing. In the late stages of the disease, a person will need help doing even simple tasks, like getting dressed.


Huntington's Disease affects the brain's basal ganglia

How do doctors diagnose Huntington's Disease?

During pregnancy, a woman can find out if her baby will have the disease with two tests: (1)taking a sample of fluid from around the fetus (amniocentesis), or (2)by taking a sample of fetal cells from the placenta (chorionic villus sampling (CVS)).

After the child is born, doctors can identify the disease by first doing a series of neurological and psychological tests. A genetic test can then confirm the diagnosis by determining if the person indeed has inherited the HD gene mutation (an expansion of the CAG triplet). However, the test cannot tell at what age a person will begin to get sick. Some question whether it is ethical to do the genetic test before symptoms appear. However, others wish to know their status before deciding to have children.

How is Huntington's Disease treated?

Treatments do not slow the progression of the disease, but they can help make the patient more comfortable. Medications ease feelings of depression and anxiety; others control involuntary movements. Physical or speech therapy helps HD patients lead more normal lives.

Maple Syrup Urine Disease (MSUD)

What is maple syrup urine disease (MSUD)?

MSUD Chromosome MSUD is a potentially deadly disorder that affects the way the body breaks down three amino acids: leucine, isoleucine, and valine. When they're not being used to build a protein, these three amino acids can either be recycled or broken down for energy. They are normally broken down by six proteins working together as a complex called BCKD (branched-chain alpha-ketoacid dehydrogenase).

People with MSUD have a mutation that renders one of the 6 proteins in the complex deficient. Therefore, they can't break down leucine, isoleucine, and valine. They end up with dangerously high levels of these amino acids in their blood, causing the rapid degeneration of brain cells and, if left untreated, even death.

Defects in any of the six subunits of the BCKD protein complex can cause MSUD. The most common defect is caused by a mutation in a gene on chromosome 19 that encodes the alpha subunit of the BCKD complex (BCKDHA).

How do people get MSUD?

MSUD is inherited in an autosomal recessive pattern. For a child to get the disease, he or she must inherit a defective copy of the gene from each parent. If both parents carry the MSUD gene, each of their children has a 1 in 4 chance of getting the disorder, and a 1 in 2 chance of being a carrier.

How do doctors diagnose MSUD?

In some states, all babies are screened for MSUD within 24 hours after birth. A blood sample taken from the baby's heel is analyzed for high leucine levels.

What are the symptoms of MSUD?

There is a classic form of MSUD and several less-common forms. Each form varies in its severity and characteristics. However, all subtypes of the disorder can be caused by mutations in any of the 6 genes used to build the BCKD protein complex.

A baby who has the disorder may appear normal at birth. But within three to four days, the symptoms appear. These may include loss of appetite, fussiness, and sweet-smelling urine. The elevated levels of amino acids in the urine generate the smell, which is reminiscent of maple syrup. This is how MSUD got its name. If left untreated, the condition usually worsens. The baby will have seizures, go into a coma, and die within the first few months of life.

Autosomal Recessive

How is MSUD treated?

Treatment involved dietary restriction of the amino acids leucine, isoleucine, and valine. This treatment must begin very early to prevent brain damage. Babies with the disease must eat a special formula that does not contain the amino acids leucine, isoleucine, and valine. As the person grows to adulthood, he or she must always watch their diet, avoiding high-protein foods such as meat, eggs, and nuts.

If levels of the three amino acids still get too high, patients can be treated with an intravenous (given through a vein) solution that helps the body use up excess leucine, isoleucine, and valine for protein synthesis.

Gene therapy is also a potential future treatment for patients with MSUD. This treatmentwould involve replacing the mutated gene with a good copy, allowing the patient's cells to make a functional BCKD protein complex and break down the excess amino acids.

MSUD Pathway
People with MSUD have a defective BCKD protein complex

Interesting facts about MSUD

MSUD is an extremely rare disorder; only 1 in 180,000 babies is born with MSUD. But in certain populations, the disease is much more common. Among the Mennonites in Pennsylvania, as many as 1 out of every 176 babies is born with the disorder.

Neurofibromatosis Type 1

What is neurofibromatosis type 1 (NF1)?

NF1 is a disorder characterized by the growth of noncancerous tumors called neurofibromas. Neurofibromas usually form on or just underneath the skin, as well as in the brain and peripheral nervous system. But they can also develop in other parts of the body, such as the eye.

The disorder is caused by a mutation in a gene on chromosome 17. The gene codes for a protein called neurofibromin. This protein regulates the activity of another protein, called ras, which promotes cell division. When the NF1 gene is mutated, it usually leads to a shortened version of the neurofibromin protein that cannot bind to ras or regulate its activity. As a result, the ras protein is more active. Cells are told to begin dividing and never told when to stop, causing them to form tumors.

How do people get NF1?

About half of the time, a person inherits the mutated gene from a parent. The disorder is inherited in an autosomal dominant pattern, which means that a child needs to inherit just one copy of the defective gene to get the disorder. Each child of a parent with NF1 has a 1 in 2 chance of getting the disorder.

In the other half of NF1 cases, there is no family history of the disease. The mutation is new and has likely occurred either in the child's parents during egg or sperm production, or early in embryonic development). Embryonic mutations will not be present in every cell of the body, just in some of them. But if it does happen to be in the germ cells (egg or sperm), the person can pass the defective copy to their children. New mutations in NF1 are relatively frequent because the gene is very large, making it more likely to accrue mutations.

Autosomal Dominant

What are the symptoms of NF1?

The severity and physical signs of NF1 can vary widely from patient to patient. Most people with this disorder have very distinctive café au lait spots (the color of coffee with milk), as well as freckles. The number of café au lait spots and freckles increases with age. People with NF1 also have many noncancerous tumors called neurofibromas throughout their body. Rarely, these tumors can progress into malignant cancers.

Others may also have high blood pressure, bone defects, scoliosis (curvature of the spine), learning disabilities, Lisch nodules (benign growths on the iris of the eye), and optic gliomas (benign tumors on the optic nerve that connects the eye to the brain).

Scientists don't know exactly why symptoms vary so much, even among people from the same family. But they predict that genetics has a lot to do with it. It is likely that each patient's unique genetic makeup influences the severity of his or her symptoms. That is, one or more additional genes other than NF1 might also play a role. Scientists call these "modifier genes," and they could be any of the thousands of genes in the human genome.

How do modifier genes work? Proteins encoded by modifier genes might work in the same biological pathways as neurofibromin, and therefore affect how well these pathways work. Variations in the DNA sequence of a modifier gene may alter its protein's function enough to influence the severity of NF1.

To date, scientists have not found any strong candidate NF1 modifier genes.

Other factors that may contribute to the variability observed among NF1 patients are environmental events and different mutations found in the NF1 gene itself. (Over 500 different mutations have been found, and all of them cause this disorder!)

NF1 Symptoms

How do doctors diagnose NF1?

Most of the time, the NF1 is fairly easy to diagnose by its physical symptoms (tumors or café au lait spots) or by a family history of the disorder. The café au lait spots usually appear within the first two years of a child's life.

NF1 can be diagnosed by sequencing a person's NF1 gene to identify mutations. But because of the gene's large size and the high number of possible mutations, genetic testing is usually impractical—and very expensive.

While doctors don't usually recommend genetic testing for NF1, the one exception is for people who have a family history of NF1. If another family member has been tested, and the mutation has been identified, then it becomes relatively easy to look for that same mutation in other family members. Finding the mutation would then confirm the diagnosis of NF1.

How is NF1 treated?

There is no cure or treatment for NF1, but surgery can remove tumors and correct malformed bones. In a very small percentage of cases, the tumors become cancerous. As in other cancers, these tumors are surgically removed and treated with chemotherapy or radiation (to kill cancer cells).

Pachyonychia Congenita

What is Pachyonychia Congenita?

Pachyonychia Congenita (PC) is a rare genetic disorder that primarily affects the skin, nails, and mouth. It is caused by a mutation in any one of four genes that code for keratin proteins. Keratins are proteins that form tough fibers that strengthen skin and things that grow out of the skin, such as hair and finger nails. Although mutations in different keratins can cause many disorders, only mutations in keratins 6a, 6b, 16, and 17 are linked to PC. This disorder does not affect lifespan, but patients do experience constant pain.

Gene Locations

Keratins are a family of related proteins with about 54 members. The keratin genes are located in two clusters, one cluster on chromosome 12 and another on chromosome 17.

How do People Get PC?

PC has a predictable pattern of inheritance. People with PC have a 1 in 2 chance of passing the disease to their children each time they conceive. In other words, the disorder exhibits an autosomal dominant inheritance pattern. Children have to inherit just one copy of the mutated keratin gene to exhibit symptoms.

In some cases, a person with PC will have no family history of the disease. This most commonly happens when a mutation occurs very early in embryonic development, soon after fertilization. It can also occur when a healthy parent's egg or sperm cells acquire a mutation in one of the keratin genes. The mutated gene is passed to the child, resulting in disease. In most cases, the affected child then has a 50% chance of passing PC to each of his or her children.


Normal keratin filaments form a strong structural network (left) that enables cells to withstand pressure and stretching. Mutant keratin proteins form clumps (right), resulting in weak cells that break open under pressure. Images courtesy Prof. W.H. Irwin McLean, University of Dundee, Scotland. Keratin filaments are green, and cell nuclei are blue.

What are the Symptoms of PC?

PC Photos

People with PC show a variety of symptoms, including (clockwise from top left) blisters and calluses on the feet and hands, thickened nails, cysts, bumps around hair follicles, and a thick white growth on the tongue.

While every cell in the body has the genes that are involved in PC, symptoms only appear in places where the genes are active. Thick nails are the hallmark symptom of PC. In fact, pachyonychia means "thick nails." However, the most pronounced symptom for people with PC is painful blisters and thick calluses on the soles of the feet. Without proper keratin filaments, skin cells become fragile and cannot withstand pressure or stretching. Just walking across a room can put enough pressure on the soles of the feet to burst skin cells.

Other common PC symptoms include blisters and calluses on the palms of the hands, a white growth on the tongue, and a variety of cysts. Children often have different symptoms than adults. Symptoms more common in children include bumps around hair follicles, hoarseness, and intense, short-duration ear pain. Importantly, individual symptoms and their severity can vary between patients, even within a family.

How do Doctors Diagnose PC?

There are two forms of PC, type 1 and type 2. They are distinguished by slightly different symptoms and by which keratin gene is mutated. To make a diagnosis, doctors typically look for a combination of PC symptoms. Because symptoms can vary, diagnosis is usually confirmed by genetic testing. PC is often misdiagnosed. The most common misdiagnosis for PC is onychomycosis, a fungal infection of the nails. Other common misdiagnoses are epidermolysis bullosa and palmoplantar keratodermas, two skin disorders that are similar to PC.

How is PC Treated?

There is no cure for PC, and drug therapies are limited. Patients typically manage their own symptoms. Trimming and filing nails can prevent infections. Hands and feet can be soaked and rubbed to clean off blistered skin. Keeping tender skin moist and cold is often comforting. Special shoes, canes, or crutches can decrease pressure on the feet.

Work is under way to provide better treatments for PC. A new technology involving gene silencing is providing hope for a cure. By inactivating the mutant keratin gene, researchers hope to restore keratin protein assembly and thereby strengthen skin cells.

Gene silencing is a promising new technology that may one day be used to treat PC. In one approach to gene silencing, the mutant keratin gene is turned off (1), allowing the three remaining keratin genes to produce proteins (2) that will assemble into proper filaments (3). Scientists are also working on other gene silencing approaches.

Funding provided by the Pachyonychia Congenita Project.


What is phenylketonuria (PKU)?

PKU Chromosome Phenylketonuria is a rare metabolic disorder that affects the way the body breaks down protein. If not treated shortly after birth, PKU can be destructive to the nervous system, causing intellectual disability.

PKU is caused by a mutation in a gene on chromosome 12. The gene codes for a protein called PAH (phenylalanine hydroxylase), an enzyme in the liver. This enzyme breaks down the amino acid phenylalanine into other products the body needs. When this gene is mutated, the shape of the PAH enzyme changes and it is unable to properly break down phenylalanine. Phenylalanine builds up in the blood and poisons nerve cells (neurons) in the brain.

How do people get PKU?

PKU is an autosomal recessive disorder, meaning that you need to inherit mutations in both copies of the gene to develop the symptoms of the disorder. A carrier does not have symptoms of the disease, but can pass on the defective gene to his or her children. If both parents carry one copy of the faulty gene, each of their children have a 1 in 4 chance of being born with the disease.

What are the symptoms of PKU?

Babies born with PKU usually have no symptoms at first. But if the disease is left untreated, babies experience severe brain damage. This damage can cause epilepsy, behavioral problems, and stunt the growth of the baby. Other symptoms include eczema (skin rash), a musty body odor (from too much phenylalanine), a small head (microcephaly), and fair skin (because phenylalanine is necessary for skin pigmentation).

Autosomal Recessive

How do doctors diagnose PKU?

Because PKU must be treated early, babies in every U.S. state are routinely tested for the disease. A small blood sample is taken from the baby's heel or arm and checked in a laboratory for high levels of phenylalanine.

How is PKU treated?

People who have PKU must eat a very low-protein diet, because nearly all proteins contain phenylalanine. Infants are given a special formula without phenylalanine. Older children and adults have to avoid protein-rich foods such as meat, eggs, cheese, and nuts. They must also avoid artificial sweeteners with aspertame, which contains phenylalanine.

PKU Pathway

People with PKU have a defective PAH enzyme

Severe Combined Immunodeficiency

What is Severe Combined Immunodeficiency (SCID)?

SCID ChromosomeSCID is a group of very rare——and potentially fatal——inherited disorders of the immune system. The immune system normally fights off attacks from dangerous bacteria and viruses. People with SCID have a defect in their immune system that leaves them vulnerable to potentially deadly infections.

There are several types of SCID. The most common form is caused by a mutation in the SCIDX1 gene located on the X chromosome. This gene encodes a protein that is used to build a receptor called IL2RG (interleukin-2 receptor). These receptors sit in the plasma membrane of immune cells. The receptors' job is to allow two types of immune cells—T cells and B cells—to communicate. When the gene is mutated, the receptors cannot form and are absent from immune cells. As a result, the immune cells can't communicate with one another about invaders. Too few T and B cells are made to fight off the infection, and the body is left defenseless.

Another form of SCID is caused by a mutation on chromosome 20 and is characterized by a deficiency of the enzyme adenosine deaminase.

How do people get SCID?

The most common form of SCID has an X-linked recessive pattern of inheritance, and is therefore referred to as X-linked SCID. When a gene is located on the X chromosome, males are more often affected than females. Males do not have a second X chromosome to compensate for the defective one. They need to inherit just one bad copy of the gene to have the disorder. Females, on the other hand, have two X chromosomes. If they inherit one defective X chromosome, they still have its healthy pair. They don't develop the disorder, but they still carry the faulty gene and can pass it to their children.

What are the symptoms of SCID?

Symptoms usually appear in the first few months of life. Because the immune system cannot protect the baby's body, babies with the disorder tend to get one infection after another. Some of these infections may be life-threatening, including pneumonia (lung infection), meningitis (brain infection), and sepsis (blood infection).

To make matters worse, SCID patients often don't respond to the antibiotics used to treat bacterial infections. They may suffer more frequently from ear infections, sinus infections, a chronic cough, and rashes on the skin.

Early diagnosis of SCID is very important, because without quick treatment, children with the disease aren't likely to live past age 2.

How do doctors diagnose SCID?

SCID can be identified before the baby is born either (1)by removing and testing cells from the placenta (chorionic villus sampling or CVS), or (2) by removing and testing a sample of the fluid surrounding the baby (amniocentesis).

Most babies are diagnosed with SCID in the first 6 months of life. The most common screening methods are an immune function test, and a blood test that detects low white blood cell counts, as well as low levels of immune cells (T cells and B cells).

X Linked

How is SCID treated?

Children with SCID must be careful to stay away from germ-rich environments (such as day care centers and crowded shopping malls) where they could pick up a potentially life-threatening infection.

The most effective treatment is a bone marrow transplant. Unspecialized stem cells (that will form blood and immune cells) are taken from the bone marrow of a healthy donor and injected into the SCID patient. Ideally, these new cells will stimulate the production of the needed immune cells. Transplants done within the first few months of life are most successful. The tissue must be "matched" to the patient, however, which can limit the usefulness of this therapy. Siblings make the best donors, as their cells usually have a similar genetic makeup.

Gene therapy for this disorder may soon be possible. This therapy would compensate for the faulty gene by injecting healthy copies of the gene into a patient's bone marrow stem cells.


Defects in ILR2 protein cause SCID.

Interesting facts about SCID

About 1 out of every 100,000 babies is born with SCID.

SCID is sometimes called Bubble Boy disease. In the 1970s, a boy named David Vetter had to live in a plastic bubble for 12 years because of SCID.

Sickle Cell Disease

What is sickle cell disease?

Sickle Cell Chromosome Sickle cell disease is a disorder that affects the red blood cells, which use a protein called hemoglobin to transport oxygen from the lungs to the rest of the body. Normally, red blood cells are round and flexible so they can travel freely through the narrow blood vessels.

The hemoglobin molecule has two parts: an alpha and a beta. Patients with sickle cell disease have a mutation in a gene on chromosome 11 that codes for the beta subunit of the hemoglobin protein. As a result, hemoglobin molecules don't form properly, causing red blood cells to be rigid and have a concave shape (like a sickle used to cut wheat). These irregularly shaped cells get stuck in the blood vessels and are unable to transport oxygen effectively, causing pain and damage to the organs.

How do people get sickle cell disease?

Sickle cell disease is inherited in an autosomal recessive pattern. This means that a child will not inherit the disease unless both parents pass down a defective copy of the gene. People who inherit one good copy of the gene and one mutated copy are carriers. They are clinically normal, but can still pass the defective gene to their children.

What are the symptoms of sickle cell disease?

Sickle cell disease prevents oxygen from reaching the spleen, liver, kidneys, lungs, heart, or other organs, causing a lot of damage. Without oxygen, the cells that make up these organs die. For example, the spleen is often destroyed in these patients, leading to some loss of immune function. As a result, these patients often experience frequent infections.

The red blood cells of patients with sickle cell disease don't live as long as healthy red blood cells. So people with this disorder often have low red blood cell counts (anemia), which is why this disease is commonly referred to as sickle cell anemia.

When sickle-shaped red blood cells get stuck in blood vessels, patients can have episodes of pain called crises. Other symptoms include delayed growth, strokes, and jaundice (yellowish skin and eyes because of liver damage).

Organ damage and other complications often shorten patients lives by about 30 years.

How do doctors diagnose sickle cell disease?

Most states routinely screen newborns for sickle cell disease with a simple blood test.

If the disorder is not detected at birth, a blood sample can be used in a test called hemoglobin electrophoresis. This test will determine whether a person has sickle cell disease or carries the faulty hemoglobin gene.

Autosomal Recessive
Sickle Cell

How is sickle cell disease treated?

Babies and young children with sickle cell disease must take a daily dose of penicillin to prevent potentially deadly infections. Patients also take folic acid, which helps build new red blood cells.

Doctors advise people with sickle cell disease to get plenty of rest, drink lots of water, and avoid too much physical activity.

Blood transfusions are commonly done to provide a patient with healthy red blood cells.

People with more severe cases of the disease can be treated with a bone marrow transplant. This procedure provides the patient with healthy blood stem cells from a donor, ideally a sibling.

Interesting facts about sickle cell disease

Unlike normal red blood cells, which can live for 120 days, sickle-shaped cells live only 10 to 20 days.

In the United States, the disease most commonly affects African-Americans. About 1 out of every 500 African-American babies born in the United States has sickle cell anemia.

Sickle cell disease is most common among people from Africa, India, the Caribbean, the Middle East, and the Mediterranean. The high prevalence of the defective gene in these regions may be due to the fact that carriers of a mutation in the beta-subunit of hemoglobin are more resistant to malaria. Malaria is a disease caused by a parasite transmitted by infected mosquitoes. The sometimes fatal disease, which causes recurring chills and fever, is common in hot climates.

Smith-Lemli-Opitz Syndrome

What is Smith-Lemli-Opitz syndrome (SLOS)?

SLOS Chromosome SLOS is a metabolic disorder caused by a mutation in the DHCR7 (7-dehydrocholesterol reductase) gene on chromosome 11. This gene codes for an enzyme that is involved in the production of cholesterol. People who have SLOS are unable to make enough cholesterol to support normal growth and development.

Cholesterol is an essential component of the cell membrane and tissues of the brain. A person who can't make enough cholesterol will therefore experience poor growth, developmental delays, and mental retardation. People with this disorder may also have a range of physical malformations (such as extra fingers or toes) and problems with internal organs (such as the heart or kidney).

How do people get SLOS?

SLOS is inherited in an autosomal recessive pattern. Because it is recessive, a child will not have the symptoms of the disorder unless both parents pass on a defective copy of the DHCR7 gene. This can only happen if both parents are carriers. A carrier is a person who has one good copy and one mutated copy of the DHCR7 gene, but does not experience any symptoms of the disorder. If both parents are carriers, each of their children will have a 25 percent chance of inheriting the disorder.

What are the symptoms of SLOS?

Symptoms vary from person to person, depending upon the amount of cholesterol they can produce. In addition to mental retardation and poor growth, common physical signs of SLOS are a cleft palate (a split upper lip), malformed genitals (in males), and polydactyly (extra fingers or toes).

Other symptoms that may be present at birth include: microcephaly (small head), webbing between the second and third toes, drooping eyelids, heart defects, hearing or sight loss, and difficulties feeding.

With the right medical care and proper diet a person with SLOS can experience a normal life expectancy, although independent living is unlikely due to mental retardation. Sadly, children with the most severe cases of SLOS (produce almost no cholesterol) usually die a few months after birth.

How do doctors diagnose SLOS?

An ultrasound (a machine that uses sound waves to look inside a mother's uterus) can reveal the hallmark physical deformities before a baby is born. Amniocentesis and chorionic villus sampling (CVS) can also determine whether the baby will be born with SLOS.

After birth, a blood test can determine whether someone has the disorder. The test looks for low levels of cholesterol, as well as higher-than-normal levels of a precursor of cholesterol.

How is SLOS treated?

There is no real treatment for SLOS, but cholesterol supplements can improve children's growth and development. Surgery may be necessary to correct some of the physical deformities (cleft palate, heart defects) associated with the disorder.


Interesting facts about SLOS

In the United States, about 1 out of every 20,000 babies is born with SLOS.

SLOS was initially named RSH, for the initials of the first three patients diagnosed with the disorder. It was later changed to honor the three geneticists (David Smith, Luc Lemli, and John Opitz) who first described the disorder in 1964.

Autosomal Recessive
  • Funding

    Funding provided by grant 51006109 from the Howard Hughes Medical Institute, Precollege Science Education Initiative for Biomedical Research.

APA format:

Genetic Science Learning Center. (2014, February 15) Single Gene Disorders. Retrieved February 09, 2018, from

CSE format:

Single Gene Disorders [Internet]. Salt Lake City (UT): Genetic Science Learning Center; 2014 [cited 2018 Feb 9] Available from

Chicago format:

Genetic Science Learning Center. "Single Gene Disorders." Learn.Genetics. February 15, 2014. Accessed February 9, 2018.