Schimke Immuno-osseous Dysplasia (SIOD)

What is SIOD?

Schimke immuno-osseous dysplasia (SIOD) is an extremely rare genetic disease that affects multiple systems in the body, including the kidneys, growth plates and cartilage, heart and arteries, lungs, and immune system. SIOD occurs when both a mother and a father carry an abnormal gene. It affects approximately 1 in 1 million to 2 million babies born in North America. SIOD is either severe with early-onset symptoms starting as an infant, or mild with late-onset symptoms starting in the teen years.

What are the signs that my child has SIOD?

Nearly all children with SIOD are short-statured, the first obvious sign. Short stature is caused by a skeletal disorder called spondyloepiphyseal dysplasia, where the bones in the spine, arms, and legs do not fully develop. A doctor might also notice that your child is failing to grow properly or has immune system problems (e.g., a T-cell deficiency leading to a weak immune system that leaves your child vulnerable to serious infections). Fatigue and kidney disease are also common signs of SIOD.

How else does SIOD affect my child’s body?

Children with SIOD typically do not respond to treatment with steroids for kidney disease, which can result in kidney failure. Nearly half of children with SIOD will have vascular disease that can result in a stroke or recurrent migraine headaches. Older children and young adults with SIOD may also experience congestive heart failure and lung disease. There is also an increased risk of developing cancers, such as those of the blood system.

What is the life expectancy for children with SIOD?

When SIOD is severe and the kidney disease is not treated with a transplant, children historically do not live past the average age of 9.2 years. However, their lifespan is likely significantly longer if their kidney disease is treated. Children with milder symptoms can live into adulthood.

How is SIOD diagnosed?

Most cases of SIOD are diagnosed by the age of 6, when a doctor notices typical signs of SIOD. To confirm SIOD, our team of doctors perform a detailed exam and evaluation with specialized tests, including x-rays to view your child’s bones, MRI and CT scans to assess bone health, and genetic testing to detect mutations in your child’s genes.

How has SIOD been treated traditionally?

Traditional treatment for SIOD involves simply managing symptoms. When kidney failure progresses, children must receive dialysis and eventually a kidney transplant to stay alive. Stem cell transplants can also be used to treat immunodeficiency and blood abnormalities. Here at Stanford Medicine Children's Health, we have developed a revolutionary new treatment, called a dual immune/solid organ transplant (DISOT).

What’s the risk of transplants in general? How do you eliminate this risk?

When a child receives a transplanted organ, such as a kidney, he or she is given anti-rejection medication to reduce the risk of rejection of the graft. Medications are used to suppress the immune system to keep it from rejecting the donated organ. Yet this constant battle between the immune system of the body and the transplanted organ may lead to loss of the transplant after only 10–12 years, even if the transplant recipient reliably takes immunosuppressive medications. Our unique approach to treating SIOD (and certain other diseases), called DISOT, appears to solve this dilemma.

What is Stanford Medicine Children’s Health’s unique approach to treating SIOD?

We offer a novel approach to treating SIOD that’s a potential cure for the kidney disease and immune problems caused by SIOD. This treatment is called a dual immune/solid organ transplant (DISOT). It is a two-transplant approach—a haploidentical stem cell transplant, which provides your child with a new immune system, followed by a kidney transplant from the same donor, usually a parent. Since your child’s new immune system recognizes its new kidney, it is less likely to reject it. DISOT was recently featured in the New England Journal of Medicine.

Have you tried this approach with other children? How are they doing?

Of the first three children treated with our dual immune/solid organ transplant (DISOT) at Stanford Children’s Health, all three were successfully transplanted and all three achieved full donor engraftment—meaning the transplanted stem cells grew into healthy cells, including those that are part of the immune system. The three children, two of whom are siblings, achieved normal kidney function without the use of long-term anti-rejection medicines.

What is a haploidentical stem cell transplant?

Finding a fully matched stem cell donor is often a challenge, leaving children to wait sometimes years for a donor. Instead, our doctors use a partially matched donor who is more readily available, usually a parent. We then selectively eliminate alpha/beta T-cells (the immune system’s fighter cells) from the donor’s stem cells to reduce the risk of graft-versus-host disease, which is otherwise a frequent complication of these kinds of transplants. This revolutionary stem cell transplant method is led by Alice Bertaina, MD, PhD—the worldwide pioneer and foremost expert in alpha/beta T-cell depleted haploidentical stem cell transplantation. Even though alpha/beta T-cells are removed, they recover 60–90 days after transplant, so your child regains his or her full immune function. 

What’s the expected benefit of Stanford Medicine Children's Health’s unique DISOT approach?

Our dual immune/solid organ transplant (DISOT) is potentially a cure for SIOD. When a new immune system is adopted from a donor—one that recognizes the transplanted kidney as its own—the possibility of chronic rejection of the kidney appears to be eliminated, along with the need for long-term medication. The body is no longer in a state of constantly fighting itself, and children treated with this method are experiencing more energy and less fatigue. By removing the need for medication, doctors also remove toxicities associated with these medications. Without medications and long hours of dialysis, quality of life for children is often improved.

Why choose Stanford Medicine Children’s Health for SIOD treatment?

• We are currently the only children’s hospital in the world to offer DISOT, which gives hope to parents who experienced little before.
• With DISOT, we offer a chance at a cure of the kidney disease and immune problems.
• We are experts at what we do. Stanford Children’s Health has performed over 1,000 stem cell transplants since the program’s inception, and we are national leaders in kidney transplant volumes.
• Our program in alpha/beta T-cell depletion is the biggest in the country.
• We participate in groundbreaking research in SIOD. Immunologist David B. Lewis, MD, heads up our SIOD research lab (in partnership with the Kruzn for a Kure Foundation), which is working to understand the cause of SIOD and its effects on the body, including its immune response (T-cells). He is part of a team of researchers across the world studying SIOD. Defects in the DNA code for the SMARCAL1 gene result in SIOD. The SMARCAL1 gene encodes a protein that helps DNA copy itself efficiently. This ability is very important, since our bodies constantly replace and renew cells throughout the body. Dr. Lewis and others are studying how the genetic deficiency of SMARCAL1 relates to the symptoms of SIOD and investigating related treatments to help heal children with SIOD.
• Your child receives care from a multidisciplinary team of internationally and nationally respected stem cell and kidney transplant specialists, nephrologists, neuroimmunologists, oncologists, and other specialists.

Where can I meet other parents of kids with SIOD?

We recommend visiting the Kruzn for a Kure Foundation, set up by parents of two of our patients, where you will learn more about SIOD and meet other children with SIOD.

Want your child to be evaluated for DISOT?

Have your child’s nephrologist contact us at (650) 498-4905.