WHAT IS SDS?

Shwachman-Diamond Syndrome (SDS) is characterized by low blood counts, increased risk of leukemia, and digestive problems due to malfunction of the pancreas. The condition is named for Boston Children's Hospital doctors Harry Shwachman, MD, and Louis Diamond, MD, who described the condition in 1964.

 

The mission of the Shwachman-Diamond Syndrome Registry (SDSR) is to partner with patients and families with SDS to develop a unique resource to improve the diagnosis, treatment and ultimately to develop a cure for children and adults with SDS. While the majority of individuals present with symptoms in childhood, increasing numbers of adults are diagnosed with SDS due to improved awareness of this condition.  Since SDS is rare, the SDSR provides a way for any patient with SDS or an SDS-like condition to share information and samples to enable research to find a cure.

What are the signs and symptoms of SDS?

SDS most often affects the bone marrow, pancreas, and bones resulting in low blood counts, difficulty digesting food, frequent infections, irregularities in bone formation and growth, and increased risk of leukemia.  Additional medical complications may also develop. Though clinical features vary in severity from patient-to-patient, common symptoms include:

Low blood counts

​Patients with SDS often have decreased function of their bone marrow, which is the factory that makes your blood. This can lead to:

  • Low neutrophil counts (neutropenia): may lead to increased risk of bacterial or fungal infections

  • Low platelet counts (thrombocytopenia): may lead to increased risk of bleeding

  • Low red blood cell counts (anemia): may lead to fatigue and/or shortness of breath

Patients may also present with myelodysplastic syndrome (MDS) or leukemia as their first sign of SDS.

Difficulty digesting food

Patients with SDS often have difficulty digesting food due to low levels of enzymes released by the pancreas that help with digestion. This can lead to:​

  • Frequent, loose bowel movements​

  • Greasy or floating stools

  • Poor growth

  • Low levels of vitamin A, vitamin D, vitamin E, or vitamin K​

Bone issues

  • Malformed bones (metaphyseal dysostosis)

  • Narrow or flared rib cage

  • Low bone density (osteopenia)​

Neuropsychological

  • Behavioral/Learning difficulties

  • Attention disorders

  • Developmental delay

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​Some patients with SDS may experience additional symptoms including those associated with the bones, liver, immune system, heart, eczema and other organ systems. However, some patients with SDS may lack apparent symptoms for a long time. Early diagnosis of SDS allows treatment prior to the development of irreversible complications.

Function of the bone marrow

The bone marrow functions as a factory to produce your body's blood cells. In SDS, the bone marrow fails to function properly, resulting in a decrease of some or all types of blood cells which may be mild or in some patients can be severe. In some patients with SDS the bone marrow acquires changes that cause leukemia to develop.  For this reason, develops blood cell counts should be monitored regularly through routine blood draws and bone marrow exams.

What causes SDS?

Genetics

Shwachman-Diamond Syndrome is most often caused by mutations in the SBDS gene which are seen in approximately 90% of patients with SDS. This gene encodes the SBDS protein which helps build ribosomes. Ribosomes synthesize proteins.

 

Other rare genes in which mutations lead to diseases with features of SDS include: DNAJC21, EFL1, and SRP54.​​

 

In about 10 percent of patients with SDS, the genetic cause has not yet been identified. With the help of registry participants, the SDS Registry is investigating potential new genes causing SDS.

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Source: ProProfs

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Inheritance

SDS caused by SBDS mutations is inherited in an autosomal recessive manner. All affected individuals inherit two copies of the mutated gene, usually one from each of their parents. The parents, who each have one altered gene, are known as carriers and do not have SDS. Therefore, when two carriers of the SBDS mutation have children, there is a 25% chance their child will have Shwachman-Diamond Syndrome.

How is SDS diagnosed?

Diagnosis

  • Genetic testing​

  • Blood counts

  • Exocrine pancreatic testing (trypsinogen, pancreatic isoamylase)

  • Stool elastase

Additional medical evaluation at diagnosis may include:

  • Bone marrow exam

  • Blood tests including: liver tests, vitamin levels and nutritional tests, endocrine tests, immunology evaluation

  • Radiology imaging may be considered for some patients: skeletal x-rays ultrasound of the pancreas/liver

  • Neurocognitive evaluation

What are the treatment options?

Treatment for SDS consists of regular monitoring for known problems associated with SDS and controlling active symptoms, often with care from specialists in hematology, gastroenterology, endocrinology, immunology and orthopedics.

To maintain optimal health, regular evaluations may be needed including:

  • Regular monitoring of blood counts

  • Monitoring bone marrow

  • Monitoring growth and nutrition

  • Monitoring liver labs

  • Evaluation of any bone abnormalities or symptoms

  • Immunology screening and referral to immunologist if clinical concerns

  • Referral to endocrinology if clinical concerns

  • Regular dental visits​

Treatment may include:

  • Pancreatic enzyme replacement- to aid in digestion and absorption of food

  • Supplements for vitamin A, vitamin D, vitamin E, and vitamin K

  • Granulocyte colony stimulating factor (G-CSF or filgrastim)- to stimulate the bone marrow to make more neutrophils

  • Blood transfusions- for patients with severely low or symptomatic anemia (low red blood cells) or thrombocytopenia (low platelets)

  • Hematopoietic stem cell transplantation for severe bone marrow failure, MDS or leukemia

  • Orthopedic surgery- depending on the patient's skeletal issues

Sources Cited:

Shwachman-Diamond syndrome - Genetics Home Reference - NIH. (2020, July 28). Retrieved August 10, 2020, from https://rarediseases.info.nih.gov/diseases/4863/shwachman-diamond-syndrome

Nelson A, Myers K. Shwachman-Diamond Syndrome. GeneReviews. Updated Oct. 18, 2018; http://www.ncbi.nlm.nih.gov/books/NBK1756/.

Myers KC, Bolyard AA, Otto B, Wong TE, Jones AT, Harris RE, Davies SM, Dale DC, Shimamura A. Variable clinical presentation of Shwachman-Diamond syndrome: update from the North American Shwachman-Diamond Syndrome Registry. J Pediatr. 2014 Apr;164(4):866-70. doi: 10.1016/j.jpeds.2013.11.039. Epub 2013 Dec 31. PMID: 24388329; PMCID: PMC4077327.

Myers KC, Davies SM, Shimamura A. Clinical and molecular pathophysiology of Shwachman-Diamond syndrome: an update. Hematol Oncol Clin North Am. 2013 Feb;27(1):117-28, ix. doi: 10.1016/j.hoc.2012.10.003. Epub 2012 Nov 3. PMID: 23351992; PMCID: PMC5693339.

Dror Y, Donadieu J, Koglmeier J, Dodge J, Toiviainen-Salo S, Makitie O, Kerr E, Zeidler C, Shimamura A, Shah N, Cipolli M, Kuijpers T, Durie P, Rommens J, Siderius L, Liu JM. Draft consensus guidelines for diagnosis and treatment of Shwachman-Diamond syndrome. Ann N Y Acad Sci. 2011 Dec;1242:40-55. doi: 10.1111/j.1749-6632.2011.06349.x. PMID: 22191555.