Case Highlights Need to Identify More aHUS-causing Mutations

Case Highlights Need to Identify More aHUS-causing Mutations
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Research is needed to identify more mutations that cause atypical hemolytic uremic syndrome (aHUS), as well as to establish best practices for long-term treatment with Soliris (eculizumab), a case report highlights.

The study, “A Case Report of Atypical Hemolytic Uremic Syndrome in a Two-Month-Old Infant With a Negative Reported Genetic Profile and Five-Year Follow-Up on Eculizumab,” was published in the journal Cureus.

aHUS is a form of thrombotic microangiopathy, a condition in which blood clots form inside the small blood vessels of several organs, particularly the kidneys. The disease is usually caused by the overactivation of the complement system, which is part of the body’s immune system. Often, but not always, this is the result of mutations in complement-associated genes.

Soliris, developed by Alexion, is an approved antibody-based treatment for aHUS that works by inhibiting the activity of the complement system.

In the study, investigators described the case of a male infant who, at the age of 2 months, was brought to the emergency room after four days of vomiting and diarrhea. In the emergency room, the infant experienced a seizure.

Laboratory tests revealed he had anemia and thrombocytopenia (low platelet counts), as well as other indicators of aHUS, such as the presence of schistocytes (red blood cell fragments) on blood smears.

Additional tests also ruled out other conditions, including typical HUS, leading physicians to suspect the boy might have aHUS.

“Diarrhea can occur in aHUS cases; therefore, our diagnostic suspicion was not altered by the presence of diarrhea at presentation,” the authors wrote.

The infant had a genetic test, which ultimately failed to identify any genetic mutations that have been previously linked to aHUS. The authors noted that this negative result, “more than anything, may reflect the present diagnostic limitations in detecting all existing complement pathway mutations.” In other words, the patient may have an aHUS-causing mutation, but it’s not picked up by a genetic test because the mutation has not yet been identified.

Within a day of hospitalization, the patient had another seizure, required peritoneal dialysis due to kidney failure, and intubation to aid his breathing. After four days in the hospital, while waiting for results of the genetic test, the infant began treatment with Soliris.

“The persistence of neurological symptoms and the ongoing requirement of respiratory support led to this decision,” the authors wrote.

Following treatment, his symptoms initially improved to the point that intubation was no longer required. But then, after about a month, the infant had another bout of seizures, accompanied by low platelet counts and other lab abnormalities. Physicians considered this episode a relapse.

The patient continued on aggressive therapy with Soliris, which ultimately resolved his symptoms. He was eventually able to stop dialysis and left the hospital 97 days after being admitted.

“The rationale for aggressive eculizumab therapy early in the course of the disease was related to the patient’s disease severity and the relapse episode,” they wrote.

In the subsequent five years, he had two brief relapses, which were associated with low-grade fever and viral infection. The patient currently has stage 3 chronic kidney disease (CKD), and is being treated with blood pressure and anti-seizure medications, in addition to ongoing treatment with Soliris. The boy also developed a swallowing disorder as a result of aHUS, and is currently using a gastronomy tube for feeding support.

“Although the studies on when eculizumab therapy can be safely stopped are lacking, we plan to continue this therapy due to concerns that another significant episode of relapse can lead to a substantial progression of the patient’s CKD,” they wrote.

“More research is needed to identify additional complement mutations that might contribute to aHUS and to establish standard monitoring guidelines for eculizumab therapy in pediatric patients,” the authors concluded.

Marisa holds an MS in Cellular and Molecular Pathology from the University of Pittsburgh, where she studied novel genetic drivers of ovarian cancer. She specializes in cancer biology, immunology, and genetics. Marisa began working with BioNews in 2018, and has written about science and health for SelfHacked and the Genetics Society of America. She also writes/composes musicals and coaches the University of Pittsburgh fencing club.
Total Posts: 16
Joana holds a BSc in Biology, a MSc in Evolutionary and Developmental Biology and a PhD in Biomedical Sciences from Universidade de Lisboa, Portugal. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells — cells that made up the lining of blood vessels — found in the umbilical cord of newborns.
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Marisa holds an MS in Cellular and Molecular Pathology from the University of Pittsburgh, where she studied novel genetic drivers of ovarian cancer. She specializes in cancer biology, immunology, and genetics. Marisa began working with BioNews in 2018, and has written about science and health for SelfHacked and the Genetics Society of America. She also writes/composes musicals and coaches the University of Pittsburgh fencing club.
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