Case of man, 23, highlights role of genetic predispositions in aHUS
Patient found to have mutation in MCP/CD46 gene after testing, per report
In a “challenging case,” clinicians found a mutation in the membrane cofactor protein gene, or MCP/CD46, in a 23-year-old man with atypical hemolytic uremic syndrome (aHUS). In reporting the case, the researchers stressed the “critical role of genetic testing” in patient evaluations, highlighting the need to be aware of any potential disease predispositions.
Here, the patient exhibited several cardiovascular and kidney-related complications, according to the researchers. These were acute kidney injury, a persistently low red blood cell count, and uremic pericarditis — a serious complication of chronic kidney disease that causes inflammation in the fluid-filled sac that surrounds and protects the heart.
His condition was ultimately managed with Soliris (eculizumab) and plasmapheresis, a blood-cleaning procedure, as well as hemodialysis to filter waste and excess fluid from the blood.
“This case emphasizes the importance of recognizing genetic predispositions in the context of [thrombotic microangiopathy], as it can significantly impact management strategies and prognosis,” the researchers wrote.
The case study, “Complement-Mediated Hemolytic Uremic Syndrome Due to MCP/CD46 Mutation: A Case Report,” was published in the Journal of Investigative Medicine High Impact Case Reports.
Genetic predispositions have been implicated in aHUS
aHUS is a rare type of thrombotic microangiopathy, called TMA, which is a group of conditions characterized by the formation of blood clots in small blood vessels, leading to organ damage. In aHUS, abnormal activation of the complement cascade — a part of the immune system — triggers increased inflammation and blood clotting in small blood vessels, particularly those in the kidneys. Over time, these blood clots can clog small vessels, causing damage to the kidneys and potentially leading to kidney failure.
Most people with aHUS have mutations in genes that regulate the function of the complement cascade. Mutations in several genes, including CD46, have been implicated in predisposing an individual toward developing aHUS.
Now, researchers in the U.S. described the case of a young man who sought treatment at a medical center for symptoms of chest pain, shortness of breath, and fainting. The man had a past medical history of high blood pressure, high cholesterol, kidney stones, and Bell’s palsy, a temporary neurological disorder that causes weakness or paralysis on one side of the face.
When he went to the emergency department, he was anemic, with low levels of hemoglobin — the oxygen-carrying protein in red blood cells. He also had fluid overload, a condition in which a person has too much fluid volume in the body.
The man was then transferred to the intensive care unit, where doctors noted that he had markedly elevated blood pressure and signs of acute kidney injury. He also had a buildup of fluid in both of lungs and in the sac surrounding the heart.
After blood tests came back with abnormalities, doctors diagnosed him with microangiopathic hemolytic anemia, a condition that occurs when red blood cells break down as they pass through small blood vessels.
Soliris used to slow progression of man’s end-stage kidney disease
The intensive care doctors then consulted with kidney specialists to treat the man’s severe acute kidney disease. These kidney specialists immediately started the patient on daily hemodialysis and he underwent four sessions of plasmapheresis during his hospital stay. Soliris was also started with the goal of slowing the progression of his end-stage kidney disease.
Kidney biopsy samples revealed the man had active TMA. However, the biopsy results did not explain the underlying cause of his TMA, prompting genetic testing.
Approximately five weeks after the patient was first treated, a CD46 gene mutation was found, confirming a genetic predisposition to TMA.
[This case underscores] the importance of genetic predispositions in guiding diagnosis and therapy.
The patient required several blood transfusions throughout his hospitalization due to persistent anemia. He was discharged from the hospital once his kidneys were functioning well enough that he could move from daily hemodialysis to hemodialysis three times a week. Ultimately doctors surgically connected an artery and a vein to improve dialysis access.
The researchers noted, in their report, that “the patient’s clinical presentation and laboratory findings prompted consideration of several differential diagnoses.” As such, the case “[underscores] the importance of genetic predispositions in guiding diagnosis and therapy,” the team wrote.
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