Shwachman-Diamond Syndrome

Shwachman-Diamond syndrome (SDS) is a rare, inherited bone marrow failure, characterized by a low number of white blood cells, poor growth due to difficulty absorbing food, and, in some cases, skeletal abnormalities. SDS is named for Boston Children's Hospital doctors Harry Shwachman, MD, and Louis Diamond, MD, who were among the researchers to first describe the condition in 1964. Most infants with SDS are born with the condition, with symptoms usually appearing by 4 to 6 months of age.

With modern treatment options and ongoing management, most children with SDS lead normal lives, although continued medications and regular monitoring through hospital visits are usually required. These are typically annual visits for children without any major problems or more frequently for those with complications.

Children with SDS have a small but significant chance of developing blood disorders such as myelodysplastic syndrome (MDS) or leukemia. Nearly 5 percent of children with the condition will develop leukemia, with the risk rising to 25 percent by adulthood.

In addition, recurring infections, including pneumonia, ear, and skin infections, are common. Many children with SDS also have growth problems and vitamin A, D, E, and K deficiencies.

The symptoms of Shwachman-Diamond syndrome (SDS) can vary from child to child but affects several body systems, including the bone marrow, pancreas, and skeleton, and occasionally the liver and teeth. The most common symptoms of SDS are:

• Chronic diarrhea
• Frequent infections due to low white blood cell counts
• Poor growth
• Pale skin
• Lack of energy or tiring easily (fatigue)
• Bruising, or a red or purple pinpoint rash on the face or body
• Bleeding (for example bleeding gums, nosebleeds, blood in the stool)
• Skeletal abnormalities, including growth plate changes, rib cage deformities, scoliosis (curvature of the spine), delayed tooth development, dental abscesses, cavities, and gum problems

After cystic fibrosis, SDS is the next most common cause of pancreatic insufficiency, which makes it difficult for patients to digest and absorb food.

Other signs can include:

• Anemia
• Thrombocytopenia (occurring in up to 30 percent of children with SDS)

SDS is caused by a mutation in a gene known as SBDS. SDS is a recessively inherited disorder, meaning that a child must inherit two defective copies of the gene (one from each parent) to develop the disease. In most cases, the parents show no signs of the syndrome.

Genetic tests can identify the precise mutation in about 90 percent of children with SDS. It is believed that an as-yet-unidentified gene is responsible for the remaining 10 percent.

Doctors diagnose Shwachman-Diamond syndrome (SDS) with:

• Blood work to evaluate red blood cells, white blood cells, and platelets
• Kidney, liver, and pancreatic function tests
• Pancreatic stimulation testing: to measure the ability of the pancreas to respond to secretin, a hormone involved in food absorption
• Stool collection
• Skeletal survey to evaluate bones
• Bone marrow biopsy and aspiration: marrow may be removed by aspiration and a needle biopsy under local anesthesia and conscious sedation so that the child remains calm and comfortable during the procedure. In a bone marrow aspiration, a fluid specimen is removed from the bone marrow. In a needle biopsy, marrow cells (not fluid) are removed. These methods are always used together.
• Genetic testing

After all tests are completed, doctors will be able to outline the best treatment options.

Children with SDS usually require care from specialists in hematology, gastroenterology, endocrinology, and orthopedics. Treatment of SDS includes:

• Pancreatic enzyme replacement: to help break food down into smaller, more absorbable nutrients
• Intravenous antibiotics: especially when white blood cell counts are low
• Growth factor therapy with granulocyte colony stimulating factor (G-CSF): to stimulate the bone marrow to make more white blood cells
• Orthopedic surgery: depending on specific skeletal problems
• Blood transfusion: for children at high risk of anemia and/or bleeding
• Ongoing regular dental care

Children with SDS are treated at Dana-Farber/Boston Children's Cancer and Blood Disorders Center through our Bone Marrow Failure and Myelodysplastic Syndrome Program, recognized as one of the nation’s best pediatric treatment and research programs for bone marrow failure and related conditions. Our patients have access to advanced treatments and diagnosis, including DNA mutation identification and ongoing clinical trials investigating new treatments. We collaborate closely with gastroenterologists, hepatologists, orthopedists, and other specialists who have a particular interest in SDS, drawing on Boston Children’s broad multidisciplinary expertise.

In addition to providing information and access to local and national research initiatives, our clinic offers multidisciplinary care (physician specialists, dentists, nurse practitioners, social workers) and consultative services for patients with SDS.

Dana-Farber/Boston Children's is a leading member of the SDS Registry, which works with patients to collect blood and bone marrow for SDS research. Collections and registries like this help researchers and physicians better understand genetic and molecular aspects of disease and how they relate to patients' clinical outcomes — first steps to identifying possible new treatments. In addition, Dana-Farber/Boston Children's physician-scientists are investigating the role of molecules called microRNAs, which can control how genes are expressed, in SDS.