At 5 years old, Little Isabella was once the liveliest child in kindergarten, but a persistent cough marked the turning point of her destiny. She seemed trapped by an invisible chain—hospitalized for pneumonia every month, with incessant thick nasal discharge, lingering bruises on her knees, and platelet counts in blood tests that plummeted like a roller coaster. Her parents took her to countless hospitals until a genetic test report with the words "PIK3CD gene mutation" unveiled the truth behind this "immune storm": APDS1 (PI3Kδ Overactivation Syndrome Type 1), a rare autosomal dominant primary immunodeficiency disease.
Doctors used an analogy: "Her immune system is like a car with failed brakes—unable to resist foreign pathogens, leading to repeated infections; meanwhile, it 'misjudges' and attacks her own blood cells, causing lymph nodes, liver, and spleen to swell like balloons. More critically, these patients face dozens of times higher risk of developing lymphoma than ordinary children." The statistics stunned her parents: globally, about 1 to 2 in 100,000 newborns carry such genetic defects. In China, among confirmed APDS1 patients, 100% experience recurrent infections, 85% have lymphoproliferation, and 50% develop secondary autoimmune diseases.
APDS1 caused by gene mutation remains a refractory disease with extremely limited treatment options. Due to its rarity, many hospitals are ill-equipped to manage it. "The only curative approach is hematopoietic stem cell transplantation," said Dr. Jiang from Kyoto Children's Hospital, as Isabella's father crushed the mineral water bottle in his hand. Transplantation requires first "resetting" Isabella's original immune system and rebuilding a "defense system" with healthy stem cells, but the process is as risky as walking a tightrope—infection and rejection could be fatal at any moment.
Thankfully, the China Umbilical Cord Blood Bank matched a fully compatible cord blood unit. As a leading institution in pediatric hematological disease treatment in China, Kyoto Children's Hospital has cured multiple APDS children through hematopoietic stem cell transplantation. During the pre-transplant conditioning period, Isabella's body became a "battlefield": antibiotics were administered like cannonballs to clear existing infections, and chemotherapy drugs "bombed" abnormal immune cells. The little girl, who loved drawing, sketched syringes as robots and infusion bottles as magic castles on the back of her medical records, writing: "When I recover, I want to paint a picture of the sun rising."
On March 15, 2023, as cord blood stem cells slowly flowed into Isabella's body through the infusion tube, her father outside the transplant chamber stared at the cell count on the monitor, tears dropping onto the record board. Fourteen days later, a peripheral blood chimerism test showed that the new hematopoietic stem cells had successfully engrafted, and Isabella's white blood cells and platelets began to rise steadily. Medical teams from multiple disciplines at Kyoto Children's Hospital—including otolaryngology, ophthalmology, endocrinology, gastroenterology, and nephrology—closely monitored her indicators. With decades of clinical experience, interdisciplinary collaboration, and timely treatment adjustments, they ensured her recovery. Statistics show that all APDS1 transplant surgeries completed by Kyoto Children's Hospital have achieved successful engraftment, far exceeding the international average, bringing hope to numerous APDS1 children families.
In the first year after transplantation, Isabella needed to gradually resume a normal life. Her days were filled with "follow-ups" but also illuminated by hope: weekly immunoglobulin checks, monthly lymphocyte subset analyses, and quarterly bone marrow biopsies. Once, during a blood draw, she looked at the nurse and asked: "Auntie, is my blood now as brave as little soldiers?" The nurse smiled and nodded: "Braver than ever."
Now Isabella has returned to school. In her schoolbag, besides textbooks, there is a "health diary" recording daily body temperature, diet, and medications. The doctor team at Kyoto Children's Hospital has developed a "Multidisciplinary Escort Plan" for her: immunologists adjust anti-infection regimens, nutritionists design high-protein diets to enhance immunity, and psychologists use art therapy to help her manage stress. Most reassuringly, Isabella's lymph nodes have shrunk to normal size, and her platelet count stabilizes at 150×10⁹/L (normal range 100–300×10⁹/L). The child once trapped by disease can finally run on the playground with her classmates.
"Is there still hope if transplantation is temporarily unavailable?" This is the most pressing question for many APDS1 children parents. Currently, the PI3K-δ inhibitor leniolisib (CDZ173) shows promising suppression of lymphoproliferation, but it is not yet approved in China and comes with a prohibitive cost—exceeding one million yuan annually—hindering widespread use. Meanwhile, gene therapy is on the horizon—scientists are exploring viral vectors to repair defective PIK3CD genes, with animal experiments already demonstrating immune function reconstruction.
Kyoto Children's Hospital in Beijing has never stopped advancing medical research. It actively participates in various scientific projects, collaborates with top domestic and international medical institutions and rare disease organizations, and jointly explores cutting-edge treatment strategies for APDS1. The hospital's expert team has repeatedly shared clinical research findings on APDS1 at domestic and international academic conferences, contributing to industry progress. As of 2024, Kyoto Children's Hospital has treated dozens of APDS1 children, including 13 who underwent hematopoietic stem cell transplantation—all with successful engraftment—making it the global leader in reported treatment cases.
APDS1 is characterized by diverse manifestations and high heterogeneity, making diagnosis challenging. "Early detection and intervention are critical," warns experts from Kyoto Children's Hospital. Although extremely rare, its symptoms often mimic chronic infections, leading to neglect or misdiagnosis. If a child exhibits symptoms such as "≥6 middle ear infections in a year," "persistent lymph node enlargement ≥2 cm," or "unexplained thrombocytopenia," they should undergo immune function screening and genetic testing at a comprehensive children's hospital as soon as possible. As Isabella's attending physician said: "Every APDS1 child is an angel 'misjudged' by their genes. With timely treatment, they can grow up to marry, have children, and chase their dreams like any other child."
Today, Isabella's easel displays a new painting: under the sun, a little girl with a ponytail holds her parents' hands, standing on a field of blooming sunflowers. In the corner, a small note reads: "My life has been rebooted." This is not just a child's rebirth story but a miracle of life written by medicine and love—where technology and compassion meet, the iceberg of rare diseases can be chiseled to let in a ray of hope. And Kyoto Children's Hospital is playing a pivotal role in this light, illuminating the path forward for more children.
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