Wiskott-Aldrich syndrome study shows carriers have symptoms

This article was first published in the Spring 2026 edition of the IDF ADVOCATE newsletter.

Dr. Sumathi Iyengar’s son has Wiskott-Aldrich syndrome (WAS), a rare primary immunodeficiency (PI) that can lead to bleeding problems, infections, and cancer. WAS is inherited in an X-linked recessive manner, which means that most affected individuals are male. Iyengar carries a variant in the WAS gene that she passed on to her son, but she is not diagnosed with WAS herself.

Iyengar enjoyed good health as a child growing up, but that began to change as she got older. She developed sinus infections in her teens, and when she entered her 30s, her platelets (blood cells that help with clotting) started dropping. Today, at 62, Iyengar’s platelet count is severely low, putting her at risk of prolonged bleeding.

The medical community once thought that females with one copy of gene variants for X-linked conditions were mostly just ‘carriers’—they could pass down the variant to their children, but generally did not experience the symptoms of X-linked conditions. New research dispels that medical opinion. On the heels of a 2024 study showing carriers of the gene variant that causes chronic granulomatous disease (CGD) also have CGD symptoms, comes another study describing how the health of women who carry the gene variant for WAS is affected.

Published in February 2026, the self-reported survey of 193 adult WAS carriers—mothers, sisters, daughters, grandmothers, and aunts of individuals with WAS—shows a high proportion of women who carry WAS-causing variants experience many of the same symptoms as the men in their families who are diagnosed with WAS. Many carriers reported low platelet counts (13%), eczema (13%), infections (33%), and autoimmunity (24%). Sinus, ear, skin, and lung infections were common, with most carriers requiring more than one course of antibiotics to clear infections, and 26% needing hospitalization.

The women reported autoimmune diseases like underactive thyroid (Hashimoto’s thyroiditis) and rheumatoid arthritis. A quarter of the 174 women who had children experienced miscarriages.

“Comprehensive clinical studies of WAS carriers should be prioritized to understand the frequency and characteristics of these health issues and assist carriers by defining appropriate preventive approaches, health screening, and support,” concluded the study.

Iyengar, who is a pediatrician and executive director of the Wiskott-Aldrich Foundation, a nonprofit dedicated to supporting families affected by WAS, said the study alters how both patients and healthcare providers view the condition.

“It validates what families have been saying for so many years: that carriers are affected, and therefore, empowers us,” said Iyengar.

According to survey results, WAS carriers also have mental health struggles. The survey showed 41% of respondents had anxiety, 44% depression, and 91% guilt from passing the variant to their children. Furthermore, the women reported a significant lack of genetic counseling related to their carrier status.

“It doesn’t matter if you have a son or a daughter, you transmit it to your child and you have guilt,” said Iyengar. “Scientifically, I understand everything, but that has not taken away my guilt.”

Iyengar said the survey results will inform clinical consensus for global management of WAS carriers. The Wiskott-Aldrich Foundation has 75 researchers, including 11 mental health providers, from around the world working on the guidelines, which will address both physical and mental health.

“This paper could not have come at a better time,” said Iyengar.

Most importantly, said Iyengar, the guidelines will help define under what conditions the mother or sibling of a child with WAS can be their stem cell donor in a bone marrow transplant (BMT). Will a child with WAS transplanted with stem cells from a carrier exhibit some of the symptoms of the carrier later in life? This is one of the many questions researchers need to explore, and the survey contributes to a larger body of research that could one day answer that question and others.

"The physicians have moved away from using carriers [for BMT], but not everybody. Some people still use them. So there are no guidelines, there is no standard. Each center does its own thing. Some will use the mother, some will use the sibling. If the sibling is a full match, do you use the sibling? I mean, imagine you have a full match and you have to say no because you are a carrier. That’s hard,” said Iyengar.

“Genetic counseling is another topic that needs to be addressed in the WAS carrier guidelines,” said Iyengar. The survey showed that some doctors neglected to provide carriers with information about having children who could be affected or unaffected, 37% of mothers received no guidance on genetic testing for their daughters, and nearly 34% felt like doctors didn’t adequately address their concerns about being a carrier.

“You can’t tell women, ‘Oh, you are fine, you have nothing to worry about.’ When you have children, there has to be nuanced counseling that carriers could be affected too,” said Iyengar.

The Wiskott-Aldrich Foundation, Immune Deficiency Foundation (IDF), the Primary Immune Deficiency Treatment Consortium (PIDTC), and Emory University collaborated to administer the study and publish the results.

“This is what IDF does so well. They empower us, they facilitate the communication and collaboration between the clinicians and us,” said Iyengar. “IDF helped design the survey and helped pull statistics together, and to me, this is how it’s supposed to be—patient-led advocacy organizations working together to answer questions that are pertinent to the community.”