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Shwachman–Diamond syndrome

Medically Reviewed

A genetic condition with pancreatic insufficiency, bone marrow dysfunction, and skeletal anomalies.

Overview

Shwachman–Diamond syndrome (SDS) is a rare, inherited disorder that primarily affects the bone marrow, pancreas, and skeletal system. First described in 1964 by Drs. Harry Shwachman and Louis Diamond, the syndrome is characterized by exocrine pancreatic insufficiency, bone marrow dysfunction (especially neutropenia), and skeletal abnormalities. It is the second most common inherited cause of pancreatic insufficiency after cystic fibrosis and is considered a multisystem disorder. Affected individuals often experience recurrent infections, growth failure, and hematologic complications, including an increased risk of developing myelodysplastic syndrome (MDS) or leukemia.

Causes

Shwachman–Diamond syndrome is caused by mutations in the SBDS gene located on chromosome 7q11. The SBDS gene plays an essential role in ribosome assembly and cellular stress response. Mutations in this gene lead to defective ribosome function, particularly affecting rapidly dividing cells such as those in the bone marrow and pancreas.

SDS follows an autosomal recessive inheritance pattern, meaning an affected individual inherits two copies of the mutated gene—one from each parent. Carriers (with one mutated copy) typically do not exhibit symptoms but have a 25% chance of passing the syndrome to each child if both parents are carriers.

Symptoms

The clinical presentation of Shwachman–Diamond syndrome is variable but typically includes a combination of the following:

Hematologic Symptoms:

  • Neutropenia: Low levels of neutrophils, leading to recurrent bacterial infections (most common and consistent finding)

  • Thrombocytopenia: Low platelet count, which may cause easy bruising or bleeding

  • Anemia: Low red blood cell count in some individuals

  • Increased risk of leukemia and MDS: Particularly acute myeloid leukemia (AML)

Pancreatic Involvement:

  • Exocrine pancreatic insufficiency, leading to malabsorption and steatorrhea (fatty stools)

  • Growth failure or poor weight gain in infancy

  • Fat-soluble vitamin deficiencies (A, D, E, and K)

Skeletal Abnormalities:

  • Metaphyseal dysplasia (abnormalities in the growing ends of long bones)

  • Short stature and delayed bone age

  • Chest wall or rib abnormalities

Other Features:

  • Dental abnormalities

  • Delayed puberty

  • Liver enzyme abnormalities or hepatomegaly in some cases

The severity and combination of symptoms can vary significantly even among individuals in the same family.

Diagnosis

Diagnosis of Shwachman–Diamond syndrome is based on clinical features, laboratory tests, and genetic confirmation. Diagnostic work-up includes:

  • Complete blood count (CBC): To evaluate levels of white cells, red cells, and platelets

  • Fecal elastase test: To assess pancreatic function and confirm exocrine pancreatic insufficiency

  • Skeletal X-rays: To detect metaphyseal dysplasia or other bone anomalies

  • Bone marrow biopsy: To evaluate marrow cellularity and detect signs of dysplasia or leukemia

  • Genetic testing: Molecular analysis of the SBDS gene confirms the diagnosis

Early diagnosis is important to monitor and manage potential complications, especially those involving the hematologic system.

Treatment

There is no cure for Shwachman–Diamond syndrome, and treatment focuses on managing symptoms and preventing complications through a multidisciplinary approach. Interventions include:

Pancreatic Management:

  • Pancreatic enzyme replacement therapy (PERT) to aid digestion

  • High-calorie, high-protein diet with fat-soluble vitamin supplements

Hematologic Management:

  • Granulocyte colony-stimulating factor (G-CSF) to stimulate white blood cell production in neutropenia

  • Transfusions as needed for anemia or thrombocytopenia

  • Regular monitoring for signs of leukemia or MDS

  • Hematopoietic stem cell transplantation (HSCT): The only curative option for severe marrow failure or leukemia

Skeletal and Developmental Support:

  • Orthopedic evaluations for skeletal issues

  • Growth hormone therapy in select cases

  • Physical therapy and occupational therapy as needed

Other Supportive Measures:

  • Routine vaccinations and infection prevention strategies

  • Regular follow-up with specialists including hematology, gastroenterology, endocrinology, and orthopedics

  • Genetic counseling for families

Prognosis

The prognosis for individuals with Shwachman–Diamond syndrome varies depending on the severity of bone marrow dysfunction and the risk of leukemia. With appropriate medical care and monitoring, many children with SDS can live into adulthood. However, the long-term outlook may be complicated by persistent infections, growth failure, or progression to hematologic malignancies.

Regular monitoring and early intervention are essential to improve quality of life and detect serious complications early. Advances in genetic understanding, supportive care, and bone marrow transplantation continue to improve outcomes for patients with this complex syndrome.

Medical Disclaimer

The information provided on this page is for educational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition.