Imagine atypical haemolytic uraemic syndrome or aHUS on a well know quiz show, say Mastermind. How would it look?—
The Mastermind studio lights dim slightly as Emily Bartley settles into the black leather chair, her navy blazer and white shirt impeccable, the red blood cell pin glinting under the spotlight. Her glasses catch the light as she adjusts them, and her steady hands rest on the armrests, ready for battle. The Mastermind host, with his deep, authoritative voice, announces, “And your specialist subject is atypical Haemolytic Uremic Syndrome. You have two minutes starting… now.”
Question 1: “In aHUS, what protein dysregulation is most commonly associated with uncontrolled complement activation?”
Emma’s eyes narrow for a split second, then she responds, “ Complement Factor H.”
“Correct.”
Question 2: “What is the primary organ affected by the thrombotic microangiopathy in aHUS?”
“Kidneys,” Emma says firmly, her voice steady.
“Correct.”
Question 3: ” What makes up the membrane attack complex?
Emma hesitates, her fingers twitching slightly. “Pass.”
Question 4: “What is the typical age of onset for most aHUS patients?”
“Any age, but often in childhood or early adulthood,” she replies quickly.
“Correct.”
Question 5: “Which drug, approved in 2011, is a monoclonal antibody used to treat aHUS by inhibiting the complement system?”
“Eculizumab,” Emma answers without missing a beat, a flicker of pride in her eyes.
“Correct.”
Question 6: “What is the main difference between aHUS and typical HUS in terms of causative agents?”
Emma pauses, then says, “Typical HUS is usually caused by E. coli, while aHUS is not.”
“Correct.”
Question 7: “How does aHUS differ from thrombotic thrombocytopenic purpura in terms of ADAMTS13 activity?”
Her brow furrows. “Pass.”
Question 8: “What are the three hallmark clinical features of aHUS?”
“Haemolytic anaemia, thrombocytopenia, and acute kidney injury,” Emma recites smoothly.
“Correct.”
Question 9: “What does C3 make up with in the C5 convertase of the Alternative Pathway?”
“Pass” she says, momentarily confused.
Question 10: “In which complement protein was a disease causing genetic variant first discovered? Emma bites her lip, then admits, “CFH.”
“Correct”
Question 11: “Name the syndrome that aHUS can be mistaken for in pregnancy due to similar symptoms.”
“HELLP syndrome,” she replies, recalling her research on pregnancy-related cases.
“Correct.”
Question 12: “What is the long-term prognosis for untreated aHUS?”
“High risk of end-stage renal disease or death,” Emma says gravely, her voice heavy with the weight of the disease’s impact.
“Correct.”
At this point, the timer is winding down, and the host, sensing the pressure, leans in. “And what role does… ” as the buzzer for time up sounds. “I have started so I will finish” says the question master “What role does the alternative complement pathway play in the pathogenesis of aHUS?”
Emily opens her mouth but hesitates, the complexity overwhelming her in the final seconds. “ When the alternative complement pathway is overactive in aHUS, leading to endothelial damage and microthrombi formation” she says, relief evident from the look in her eyes.
“Correct”
“Emily you have scored 10 on your specialists subject. You passed on 3 .
The Alternative Pathway C5 convertase is made up of C3bBbC3b,
aHUS different from TTP because the ADAMTS 13 in TPP are very low or non existent but not in aHUS
The membrane attack complex is made up of C5b,C6,C7,C8 and C9″.
The audience applauds, and the host nods respectfully. “An impressive performance on a challenging subject,” he says, as Emily prepares for the general knowledge round.
Article No. 736
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