About the Disease

Your blood contains many proteins, red blood cells, platelets and other things. When your blood passes thru your kidneys, small vessels (called nephrons) filter out waste. In aHUS, the walls of your blood vessels can become clogged with platelets. So when your body is filtering blood, those platelets are clotting up the kidney function (TMA).

What is the root cause of platelets clotting?

One of the proteins in your blood isn't working right. So when your red blood cells pass thru, they are shattered (shistocytes). Therefore, your platelet counts start to decrease, as does your red blood cell count. As a result, your kidney struggles very hard to do its job. As a result, wastes such as creatinine are not filtered out properly, and their levels rise.

Also, your BUN (Blood Urea Nitrogen) levels may increase. There are a number of different proteins that could be the cause. Your genes are responsible for directing the proteins, so ultimately, one of your genes is not doing its job on the assembly line in your body.

WHAT IS THE COMPLEMENT SYSTEM?

The complement system is a part of the immune system that enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promotes inflammation, and attacks the pathogen's plasma membrane.

WHY IS aHUS REGARDED AS A GENETIC DISORDER?

The root cause of aHUS lies in family genetics in most cases and what was once considered mainly a childhood disease, we now know can strike a person of any age. Some cases have not been linked to any specific gene, but it is believed that ultimately, more telltale genes will be uncovered over the next few years. The root cause of the “micro clots” we mentioned before is uncontrolled complement activation. As you now know, complement is part of our innate immune system (alternative pathway) but do not confuse it with the acquired immune system. The complement system is always ready to attack foreign invaders. However, the complement system has “referees” who control the game, so to speak and those referees mediate on behalf of the body. So, when one of the genes makes a protein that is defective, the protein refuses to “play by the rules”, and continues to attak the body when the attack is not really justified. As a result, the cell walls become injured, micro clotting occurs, and organs can become damaged.

View a medical overview of aHUS by the NIH GeneReview

Deeper Dive

Types of Hemolytic Uremic Syndrome

Hemolytic Uremic Syndrome (HUS) describes clinical scenarios in which patients have microangiopathic hemolysis, decreased platelet count, and organ damage and failure. There are two types of HUS: typical HUS (caused by E coli or other food/water borne pathogens) and atypical HUS (usually a genetic mutation but sometimes triggered by other illnesses or unknown causes).

HUS (Typical HUS)

Typical HUS (aka, Shiga-toxin–producing E. coli hemolytic uremic syndrome, or STEC-HUS) is an acquired illness resulting from exposure to E. coli bacteria or other food-borne pathogens or contaminated water, which often presents as bloody diarrhea. Triggers can range from exposure to animal fecal matter at a farm or park to those illnesses related to eating contaminated foods, such as uncooked hamburger or another unsafe food source. Such toxins can cause an immune system response that causes hemolysis (red blood cell destruction) and kidney failure, as well as damage to other body systems. In typical HUS, most cases will not occur again after the initial onset (typically lasting 4 to 6 weeks). Cases vary widely in impact and outcome, with reports ranging from complete recovery to death, but many experience some degree of long-term kidney damage, long-term neurological complications, and ongoing issues with high blood pressure. This more common type of HUS is usually related to a single event, often traceable via group exposure that affected multiple patients, and their HUS episode will not come back to make the patient ill again.

Atypical HUS  

People with aHUS are born with this genetic disease and have a lifelong risk of having their genetic condition suddenly become active with life-threatening complications. Atypical HUS occurs because of a patient’s abnormal genes at birth, and while certain conditions such as bacterial or viral exposure might be among suspected triggers, genetic mutations are the underlying cause whether the mutations are identified by genetic screening or whether the genetic tests are inconclusive. Atypical HUS is unpredictable and varies greatly in episode length, frequency of events, and severity from patient to patient. Some aHUS patients will have intermittent signs and symptoms, while others have chronic symptoms on a daily basis. Some aHUS events occur with rapid and devastating consequences. Historically, due to limited treatment options, the outlook for patients was poor as life-threatening thromboses (blood clots) could recur and could be fatal.

Atypical HUS is a rare, chronic disease in which uncontrolled complement activation causes blood clots (thrombotic microangiopathy, or TMA) in small blood vessels throughout the body. It affects various organs, including the kidneys, heart, lungs, brain, and gastrointestinal systems. The complement system is part of the human immune system, which normally helps (or complements) our ability to fight illness by attacking any foreign or invading cells. Controlled by a group of genes, our complement system is usually regulated by proteins that prevent it from becoming overactive. In aHUS, certain complement proteins are missing or not working properly, prompting the medical terms “complement dysregulation” or “complement-mediated” disease. 

Genetic screening can be conducted to identify the patient’s mutation, but approximately 30% to 50% of aHUS patients will not have an identified genetic mutation (such as factor H, factor I, membrane cofactor protein, etc), and a diagnosis of aHUS is not dependent on results of genetic tests. A disease is classified as “rare” if it affects fewer than 500 patients per million population, but aHUS bears the “ultra rare” designation reserved for diseases that affect less than 20 per million people. To put this into perspective, according to the United States Census Bureau as of April 2012, with America’s population of 312.8 million people, the number of patients with aHUS would be fewer than 625; with the world population estimated to be 7 billion, the number of patients with aHUS worldwide is estimated to be fewer than 140,000.