New advances in medical technology have improved how we identify rare genetic disorders and how we create treatments for them.
Lindsay C. Burrage, M.D., Ph.D., FACMG
Chair, Therapeutics Committee, American College of Medical Genetics and Genomics
Jerry Vockley, M.D., Ph.D., FACMG
Board of Directors, American College of Medical Genetics and Genomics
Rare genetic disorders are caused by changes, or variants, in DNA. DNA is a chemical that contains instructions for about 30,000 genes in the body. These genes tell the body how to produce RNA. RNA helps put together amino acids to make proteins, which are the “building blocks” of our cells. Variants in DNA can lead to problems with making RNA or proteins, which then can cause genetic disorders. New tools, like DNA sequencing, have made it easier to diagnose genetic disorders quickly. Because of these tools, researchers and doctors can now focus more on developing new treatments.
Phenylketonuria (PKU) is a good example of how genetic disorders can be treated. PKU happens when there are variants in the gene that makes a protein called phenylalanine hydroxylase (PAH). In people with PKU, the PAH protein does not work correctly, so it cannot turn the amino acid phenylalanine into another amino acid called tyrosine. This causes phenylalanine to build up in the blood, leading to brain damage and severe intellectual disabilities if not treated.
Luckily, if PKU is found early, it can be treated with a special diet that limits phenylalanine. This helps prevent brain damage and allows for normal development. PKU is one of many disorders that can be detected in newborns before symptoms start. Early diagnosis and treatment have greatly improved outcomes for people with PKU. However, the special diet can be expensive and hard to follow for children and adults.
Making treatment options accessible
New treatments are giving hope to people with PKU. One treatment helps the PAH protein work better. Another drug uses a different protein to lower phenylalanine levels in the blood. Scientists are also working on treatments to help the body produce normal PAH protein. These new treatments include RNA therapy and gene therapy. RNA therapy is a temporary fix that needs to be repeated over time because RNA breaks down in the cells. On the other hand, gene therapy can offer a long-term cure. Gene therapy is now becoming a reality, with new gene therapies approved for almost 2 dozen disorders. More of these treatments are expected in the coming years.
Unfortunately, these new treatments are very expensive. Developing drugs for rare disorders costs a lot of money because only a small number of people need them. As a result, the prices for these treatments can be hundreds of thousands or even millions of dollars. Rapid advances in diagnosis and the introduction of new therapies give hope to the millions of Americans living with rare disorders and to the physicians caring for them. Moving forward, doctors, patients, payers, and researchers will need to work together to make sure that available treatments are accessible to all who need them.
For individuals seeking more information on medical genetics or who want to find a medical genetics healthcare professional in their area, the American College of Medical Genetics and Genomics (ACMG) offers “Find a Member” or “Find a Genetic Service” directories. Visit www.acmg.net and then click on Directories.
