What is Shwachman-Diamond Syndrome and How is it Treated?

Classified as a form of bone marrow failure, Shwachman-Diamond syndrome (SDS) is a rare, inherited condition that is usually diagnosed in children but is increasingly diagnosed in adults. The frequency of SDS is unclear, but is estimated to affect about one in 75,000 people.

SDS is characterized by inadequate production of pancreatic enzymes, which are important for digestion, and low blood cell counts. Skeletal abnormalities and short stature may also be seen. Symptoms usually appear by four to six months of age but may not be apparent until adulthood. SDS is also associated with an increased risk of developing myelodysplastic syndrome or leukemia.

SDS was first described in 1964 by researchers including Boston Children’s Hospital physicians Harry Shwachman, MD, and Louis Diamond, MD, who later established Dana-Farber/Boston Children’s Cancer and Blood Disorders Center.

SDS is usually caused by mutations in a gene called SBDS. The condition is autosomal recessive, meaning two copies of the mutated gene — one from each parent — are necessary to cause the syndrome.  Some clinical features of SDS may also be caused by mutations in other genes such as EFL1, DNAJC21, and SRP54.

Symptoms can vary a great deal from one person to another. Common symptoms include:

  • Chronic diarrhea, particularly in early childhood
  • Elevated liver enzymes and/or liver enlargement in early childhood
  • Frequent infections
  • Impaired growth leading to short stature
  • Pancreatic enzyme insufficiency
  • Fatigue
  • Bleeding or excessive bruising
  • Skeletal abnormalities including rib cage malformation
  • Eczema
  • Myelodysplastic syndrome
  • Leukemia

Shwachman-Diamond syndrome is diagnosed through a combination of tests, including:

  • Blood cell counts
  • Exocrine pancreatic function tests
  • Liver tests
  • Skeletal evaluation
  • Bone marrow exam
  • Genetic testing

Treatment is likely to include pancreatic enzyme replacement to help with digestion of food, especially fats, and absorption of nutrients; antibiotics, which are sometimes given intravenously when white blood cell counts are low; therapy with growth factors to increase production of white blood cells; orthopedic surgery for skeletal problems; and regular dental care. 

Regular monitoring for early signs of impending leukemia should be conducted by a hematologist with expertise in SDS. The standard treatment for hematologic complications of SDS is a hematopoietic stem cell transplant/bone marrow transplant. SDS patients require tailored transplants, so consultation with a transplant center experienced with SDS is recommended.

Most children with Shwachman-Diamond syndrome who receive regular, expert treatment are able to live well with the disease. Typically, they are seen at annual medical visits, unless treatment is needed for complications. Children with SDS have an increased risk of developing blood disorders such as myelodysplastic syndrome (MDS) or leukemia.

A team of specialists, such as those at the Bone Marrow Failure and Myelodysplastic Syndrome Program at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, work together in the care of patients with SDS.

Dana-Farber/Boston Children’s has a long history of research and innovation in conditions associated with bone marrow failure. The basic science and clinical research program offers unique access to clinical trials in which children can access the newest bone marrow failure diagnostic evaluations and treatments. Dana-Farber/Boston Children’s is also the coordinating center for the national Shwachman-Diamond Registry.