Toddler with aHUS-induced Seizures Highlights Importance of Early Intervention, Case Study Says

Toddler with aHUS-induced Seizures Highlights Importance of Early Intervention, Case Study Says

A rare case of atypical hemolytic uremic syndrome (aHUS) manifesting in generalized seizures in a 14-month-old girl highlights the importance of prompt diagnosis and treatment to ensure better outcomes for this young population, a report says.

The case was described in a study, “Seizure as the Presenting Symptom for Atypical Hemolytic Uremic Syndrome,” which was published in The Journal of Emergency Medicine.

aHUS is a progressive disorder with a high risk of permanent renal damage caused by a malfunctioning of the complement system — a set of more than 20 blood proteins that contribute to the body’s natural immune defenses. About 60–70% of aHUS patients carry loss-of-function mutations affecting genes that encode these complement regulatory proteins.

This disorder more commonly shows extra-renal symptoms than typical HUS, often involving the central nervous system, with altered consciousness, seizures, irritability, drowsiness, and focal neurologic deficits. But it can also affect the gastrointestinal and cardiovascular systems, causing diarrhea and heart problems.

“Although these atypical symptoms commonly lead physicians to consider other diagnoses, aHUS should be included in the list of differential diagnoses,” said researchers at Dartmouth–Hitchcock Medical Center.

They reported the case of a 14-month-old girl who experienced vomiting, decreased appetite, and fever for four days, as well as reduced urine production and facial swelling. She had recently been exposed to gastrointestinal illness from her half-sister and upper respiratory symptoms from her mother.

Her parents took her to the hospital after she had a generalized tonic-clonic seizure (commonly known as convulsion) that lasted for 10–15 minutes.

Her family clinical history revealed that her mother had multiple urinary tract infections, and been hospitalized for pelvic thrombosis (blood clots), and unspecified liver and kidney problems during pregnancy. No conclusive diagnosis was made for her mother at that time.

At the hospital, the girl had another seizure that was resolved upon treatment with intranasal midazolam.

Laboratory analyses revealed that she had low levels of hemoglobin, hematocrit, and platelets, and evidence of disrupted red blood cells. She was also found to have slightly low levels of sodium, bicarbonate, and high blood levels of potassium, chloride, calcium, phosphorus, blood urea nitrogen, and creatinine.

Further blood analysis revealed that she had about 10 times higher levels of lactate dehydrogenase, and reduced levels of C3 and C4 complement proteins.

While a head computed tomography, electrocardiogram, and infection analysis did not show any significant alterations that could explain her symptoms, urine testing confirmed that she had impaired renal function with some changes in tissue structure.

In order to reestablish normal blood electrolyte levels, she was treated with calcium gluconate, sodium bicarbonate, insulin, and glucose infusions.

To reduce her facial edema, she was given a dose of Lasix (furosemide), but it failed to resolve her fluid build-up. Given her acute renal failure, she started on dialysis.

The clinical team suspected that she might have aHUS based on her symptoms and test results, and they started to prepare her for treatment with Soliris (eculizumab).

Soliris is a complement inhibitor developed by Alexion. It works by blocking the signals of the immune system’s complement pathway that, when activated in an uncontrolled manner, contributes to the development of rare and serious diseases such as paroxysmal nocturnal hemoglobinuria, aHUS, and generalized myasthenia gravis.

After starting treatment with Soliris, the girl’s renal function improved. She continued treatment with Soliris infusions every three weeks after she was discharged from the hospital, as she was at high risk for relapse. She was in full remission and healthy in the subsequent nine months while receiving the treatment.

However, an influenza infection triggered an aHUS relapse, causing seizures and impaired renal function. The girl received a high dose injection of Soliris to manage aHUS and Ativan (lorazepam) for seizure prevention. Her health improved significantly with the only complication being hypertension, which was resolved in the hospital.

“It is important to recognize the presenting atypical features of aHUS in the emergency department and the pediatric intensive care unit,” the researchers wrote.

“Rapid diagnosis of aHUS is especially important to optimize long-term prognosis, which can be done through administration of eculizumab (Soliris) within 48 h of symptom onset,” they said.