SNP Shot: Genomic Insights

Atypical hemolytic-uremic syndrome (aHUS) is a disease that primarily impairs kidney function. Affecting individuals of all ages, aHUS is characterized by the formation of abnormal blood clots (thrombi) in the small blood vessels of the kidneys. These clots can severely restrict or block blood flow, leading to significant medical complications. The defining features of aHUS, all related to abnormal clotting, are hemolytic anemia, thrombocytopenia, and kidney failure.

Hemolytic anemia involves the premature breakdown of red blood cells (hemolysis). In aHUS, red blood cells can rupture as they pass by clots within the kidneys' small blood vessels. If red blood cells are destroyed at a faster rate than the body can replace them, anemia develops. Anemia can manifest as unusually pale skin (pallor), yellowing of the skin and eyes (jaundice), fatigue, shortness of breath, and a rapid heartbeat.

Thrombocytopenia refers to a decreased number of platelets in circulation. Platelets are cells crucial for normal blood clotting. In aHUS, the excessive formation of abnormal clots consumes a large number of platelets, leading to a reduced platelet count in the bloodstream. This can result in easy bruising and abnormal bleeding.

The formation of clots in the kidneys' small blood vessels causes kidney damage and acute kidney failure in individuals with aHUS. Approximately half of all aHUS cases progress to end-stage renal disease (ESRD). This life-threatening complication impairs the kidneys' ability to effectively filter fluids and waste products from the body.

Atypical hemolytic-uremic syndrome should not be confused with typical hemolytic-uremic syndrome, a more common condition. These two disorders have distinct causes and symptoms. Unlike aHUS, typical HUS is caused by infection with specific strains of Escherichia coli bacteria that produce toxic substances called Shiga-like toxins. Typical HUS is usually associated with severe diarrhea and primarily affects children under 10 years of age. Compared to aHUS, typical HUS is less likely to cause recurrent episodes of kidney damage leading to ESRD.

Inheritance:

Most cases of atypical hemolytic-uremic syndrome (aHUS) are sporadic, meaning they occur in individuals without a family history of the condition. Familial aHUS, where the disorder runs in families, accounts for less than 20% of all cases. Familial aHUS can be inherited in either an autosomal dominant or autosomal recessive pattern.

Autosomal dominant inheritance implies that only one copy of a mutated gene in each cell is needed to increase the risk of developing the disorder. In some instances, an affected individual inherits the mutation from a parent who also has the condition. However, many individuals with autosomal dominant aHUS have no family history of the disorder. Because not everyone who inherits the gene mutation develops the disease, some individuals may have unaffected relatives who carry the same mutation.

Autosomal recessive inheritance signifies that both copies of a gene in each cell must carry mutations for the condition to manifest. The parents of an individual with an autosomal recessive disorder each carry one copy of the mutated gene, but they usually do not exhibit any signs or symptoms of the condition.