Welcome to the Rare Classroom, a new series from Patient Worthy. Rare Classroom is designed for the curious reader who wants to get informed on some of the rarest, most mysterious diseases and conditions. There are thousands of rare diseases out there, but only a very small number of them have viable treatments and regularly make the news. This series is an opportunity to learn the basics about some of the diseases that almost no one hears much about or that we otherwise haven’t been able to report on very often.
Eyes front and ears open. Class is now in session.
The disease that we will be learning about today is:
Atypical Hemolytic Uremic Syndrome
What is Atypical Hemolytic Uremic Syndrome?
- Atypical hemolytic uremic syndrome (aHUS) is a disease that causes abnormal blood clots to form in small blood vessels in the kidneys. These clots can cause serious medical problems if they restrict or block blood flow, including hemolytic anemia, thrombocytopenia, and kidney failure.
- This disease affects 1 to 2 of every million Americans. The illness causes dysfunction of the complement system. Blood vessels are often damaged and can cause excessive platelet activity.
- In childhood, aHUS affects males and females in equal numbers. In adulthood, females are affected more often than males, most likely because pregnancy is a triggering event.
- In Europe, the disorder is estimated to affect approximately .11 per 1 million individuals between the ages of 0-18. aHUS accounts for approximately 5-10% of all cases of hemolytic uremic syndrome.
How Do You Get It?
- It can occur at any age and is often caused by a combination of environmental and genetic factors.
- In most cases, aHUS is related to gene mutations, coupled with a triggering event. Just having a gene mutation alone usually will not cause the disease. You need a gene mutation and a triggering event for a flare-up to start. Some examples of aHUS triggers are:
- Pregnancy
- Infections (from viruses and/or bacteria)
- Cancers
- Certain medicines
- In other more rare cases, aHUS is related to the development of antibodies that attack your body’s own immune system. The reason some people develop these antibodies is unknown.
- In aHUS cases where gene mutations and antibodies are not involved, the cause is not known. Many researchers think that cases of aHUS where the cause is unknown are linked to mutations in genes that have not yet been discovered.
- A number of genetic mutations have been linked to this disease including:
- CFH – accounting for approximately 30% of cases.
- CD46, also known as MCP – accounting for approximately 12% of cases.
- CFI – accounting for approximately 5%-10% of cases.
- C3 – accounting for approximately 5% of cases.
- CFB – extremely rare, <2% of cases.
- THBD – accounting for approximately 3% of cases.
- DGKE – accounting for approximately 27% of cases with onset before age of 1 year. It is considered a distinct disorder by some researchers because this gene does not encode for a complement protein or complement regulatory protein.
- One or two additional factors may be required for development of aHUS – an environmental trigger and a second genetic abnormality.
- In most patients, there is a triggering event such as an acute infection. Pregnancy is a common trigger in women.
- A genetic modifier could be a mutation in a second complement gene or the presence of a polymorphism that increases the risk of uncontrolled activation of the complement system.
What Are The Symptoms?
- The onset of symptoms can occur at any age and can occur very gradually to very suddenly.
- Early impacts include overactive platelets and damage to blood vessels.
- Overactive platelets can trigger symptoms of thrombotic microangiopathy (TMA)
- TMA symptoms can include:
- Bloody stool or urine
- Small red, purple, or brown spots on the skin
- Bruises
- Prolonged bleeding
- Confusion
- Weight loss or gain
- Difficulty breathing
- Paleness
- Jaundice
- Fatigue
- Dark urine
- Low urine output
- Listlessness
- Uremic encephalopathy
- Vomiting
- Nausea
- Swelling
How Is It Treated?
- Treatment by a medical team familiar with the unique challenges of aHUS is recommended and can include pediatricians or general internists, kidney specialists (nephrologists), intensive care physicians, nurses, nutritionists and social workers.
- Blood transfusions are administered when the hemoglobin level is below 7 g/dl. Platelet transfusions are avoided if at all possible. Drugs that expand the blood vessels (vasodilators) are used to control blood pressure (hypertension).
- Plasmapheresis in conjunction with drugs that suppress the immune system (immunosuppressive therapy) can be used to treat individuals with aHUS due to autoantibodies to factor H.
- In 2011, the U.S Food and Drug Administration (FDA) approved the use of the humanized anti-C5 monoclonal antibody eculizumab as a treatment for acute hemolytic uremic syndrome. In 2019 (FDA) approved ULTOMIRIS ® (ravulizumab-cwvz) for the treatment of atypical hemolytic uremic syndrome (aHUS)
- aHUS is commonly treated with a drug called eculizumab. For now, it is the only medicine approved in the United States to treat aHUS. Eculizumab can improve platelet and red blood cell counts. It may also reverse acute kidney injury and prevent kidney failure if it is taken soon enough. Eculizumab is given by injection at a doctor’s office.
- Other drug treatments used for this disease include:
- Ravulizumab-cwvz
- Narsoplimab
- Avacopan
- Plasma therapies including infusions and exchanges are sometimes used to treat aHUS, but these methods do not treat the underlying disease. Plasma therapies work for treating aHUS in some people, but do not work for everyone.
- For years, plasma therapy was the standard treatment for individuals with aHUS. Both infusions of fresh frozen plasma (plasma infusion) as well as plasma exchange (plasmapheresis) were utilized.
- Fresh frozen plasma is a blood derivative that is obtained from donors.
- Plasma exchange is a method for removing potentially harmful substances (e.g. toxins, metabolic substances, and plasma parts) from the blood.
- Blood is removed from the affected individual and blood cells are separated from the plasma.
- The plasma is then replaced with other human plasma and the blood is transfused into the affected individuals. Plasma exchange can also remove mutant factors and autoantibodies.
- Individuals who fail to recover kidney function after treatment may require a kidney (renal) transplant.
Where Can I Learn More???
- Check out our cornerstone on this disease here.
- Learn more about this illness from the National Organization for Rare Disorders.
