Shwachman-Diamond Syndrome

Earn CME/CE in your profession:

Continuing Education Activity

Schwachman-Diamond syndrome (SDS) is an autosomal recessive disorder that is the second most common cause of exocrine pancreatic insufficiency after cystic fibrosis. It presents with the common triad of exocrine pancreatic dysfunction, skeletal abnormalities, and bone marrow dysfunction. However, cardiac abnormalities, immune dysfunction, and hematologic disorders are also reported. A mutation in the Shwachman-Bodian-Diamond syndrome (SBDS) gene on chromosome 7 is found in 90% of the cases. This activity reviews the clinical presentation, diagnostic workup, management, and potential complications of this disorder and highlights the role of the interprofessional team in caring for affected patients.


  • Explain the etiology of Schwachman-Diamond syndrome.
  • Review the evaluation for Schwachman-Diamond syndrome.
  • Outline the treatment and management options available for Schwachman-Diamond syndrome.
  • Summarize interprofessional team strategies for improving care coordination and communication to advance care for patients with Schwachman-Diamond syndrome and improve outcomes.


Schwachman-Diamond syndrome (SDS) is an autosomal recessive disorder that is the second most common cause of exocrine pancreatic insufficiency after cystic fibrosis. It presents with the common triad of exocrine pancreatic dysfunction, skeletal abnormalities, and bone marrow dysfunction. However, cardiac abnormalities, immune dysfunction, and hematologic disorders are also reported. A mutation in the Shwachman-Bodian-Diamond syndrome (SBDS) gene on chromosome 7 is found in 90% of the cases.[1][2][3][4]


SDS is caused by an SBDS gene mutation on chromosome 7. It codes for the SBDS protein (SBDSP), which is widely expressed, throughout the body, in different organ systems. SBDS gene and SBDSP pseudogene are located in proximity on chromosome 7, and a possible conversion event between the 2 loci result in the mutation.[5][6][7]


It is a rare disorder with a reported incidence of 1 in 75,000 individuals. Patients generally present in infancy. Life expectancy into the third and fourth decades of life is reported in the literature. There is a higher incidence of males affected with a male to female ratio of 1.7:1.


SBDS gene codes for the SBDS protein. The protein is found predominantly in the nucleolus and is implicated in the normal functioning of ribosomes, amplification of the centrosomes, and in leukemogenesis. However, the true function of the SBDS protein is still unknown. In the pancreas, there is the fatty replacement of the acinar cells, which results in an exocrine deficiency. Cytopenias result in stress hematopoiesis in the bone marrow, which accounts for the elevated levels of hemoglobin F. The exact mechanism behind malignant transformation into acute myelogenous leukemia (AML) is unknown.  The abnormalities in the hematological system may be absent on initial presentation but can manifest later as part of an evolving process.[8][9][10]

History and Physical

SDS is thought to be underdiagnosed in the general population due to its ambiguous presentation. It can present at any time in life, though most cases present earlier in life. Predominantly, patients present with exocrine pancreatic insufficiency and hematologic abnormalities; other manifestations are less common. Steatorrhea, malabsorption, and deficiency of fat-soluble vitamins are the hallmarks of exocrine pancreatic insufficiency; however, most of these symptoms improve with age in most patients.

Hematologic abnormalities are also common in patients with SDS. Leukopenia results in recurrent viral and bacterial infections, including but not limited to sinusitis, pneumonia, osteomyelitis, and septicemia. Patients can present with bleeding, sometimes life-threatening, due to thrombocytopenia. Macrocytic or normocytic anemia is also seen in up to 80% of patients.  

Patients can also present with manifestations of skeletal abnormalities. These include short stature, rib-cage abnormalities, slipped femoral epiphysis, spinal, and finger deformities.

Neurological abnormalities, including intellectual disability, depressed attention span, difficulty in executive functioning, and impaired visual motor coordination, can also be present. Behavioral changes are also reported in children with SDS.


Presence of hematological abnormalities and exocrine pancreatic insufficiency are needed to make a clinical diagnosis of SDS, according to the latest guidelines. However, other causes of bone marrow failure and exocrine pancreatic insufficiency should be excluded.

Patients with suspected exocrine pancreatic insufficiency should have a 72-hour stool fat quantification test performed. Trypsinogen and isoamylase levels aid in the diagnosis; however, trypsinogen levels can only be measured before three years of age as levels start increasing after three years; whereas, isoamylase levels always remain low. A sweat chloride test is normal in these patients, and this distinguishes between SDS and cystic fibrosis.

Routine blood workup can provide information about cytopenias. Patients with SDS need frequent monitoring of blood for early detection of progression to myelodysplastic syndromes or acute myelogenous leukemia (AML). 

Genetic testing for mutations of the SBDS gene can confirm the diagnosis in 90% of the cases. Upon confirmation of diagnosis, a bone marrow biopsy, aspirate smear, cytological testing, and a skeletal survey is recommended.

Referral to a specialist should be made if any neurocognitive deficit is suspected.

Treatment / Management

Upon confirmation of diagnosis, patients should be initiated on a pancreatic enzymatic replacement. This is shown to generate a good response in these patients. Levels of fat-soluble vitamins should also be checked regularly (every 6 to 12 months) and replaced as necessary. The exocrine pancreatic function should be checked as it improves with time, and enzymatic replacement may need to be discontinued. Additionally, patients should have dietary counseling provided by a certified dietitian with regular monitoring of growth by serial height and weight measurements.

Transfusions of packed red blood cells (PRBC) and platelets are the mainstay of management for anemia and thrombocytopenia, respectively. In patients requiring extensive PRBC transfusions, initiation of iron chelation needs to be considered.

Infections are the feared complication of leukopenia. Prompt treatment with antibiotics is the mainstay of therapy. Granulocyte colony-stimulating factor (G-CSF) can be used to increase the white blood cell (WBC) count. However, it is not needed in most patients. It can be used in patients with severe neutropenia or patients with frequent invasive infections. The goal of G-CSF administration is to reduce the incidence of infections and not to achieve normal laboratory hematological values. There is some concern about G-CSF use causing myelodysplastic and leukemic transformation in the bone marrow, but there is a lack of strong evidence to prove it.

Patients should have routine blood monitoring every 3 to 4 months with a hematologist for detection of marrow failure, myelodysplastic syndrome, or leukemia. Due to the rarity of the disease, there is no particular chemotherapeutic regimen approved for these patients. Chemotherapy only serves to contain the disease process and is not curative in SDS patients with leukemia. Hematopoietic stem cell transplant (HSCT) is the only curative treatment in these patients. The indication for receiving HSCT determines survival. Patients receiving HSCT for bone marrow failure (e.g., aplastic anemia) have been reported to fare better than patients receiving HSCT for leukemia.

Patients with SDS are more likely to have complications from chemotherapy and HSCT than patients with isolated hematological problems requiring similar treatments. These include infections, persistent aplasia, cardiotoxicity, and renal failure.

Follow-up of the skeletal system is determined by the findings of the initial skeletal survey performed at the time of diagnosis. Patients with SDS should be monitored for osteoporosis. Vitamin D levels should be checked and maintained within normal limits.

Patients with SDS should have regular developmental neuropsychological evaluations from ages 5 to 18 to assess for adequate brain maturation.

Differential Diagnosis

  • Cystic fibrosis 
  • Pearson syndrome 
  • Pancreatic agenesis 
  • Johanson-Blizzard syndrome 
  • Cartilage-hair hypoplasia


  • Hematology/oncology 
  • Gastroenterology 
  • Orthopedic surgery 
  • Psychologist

Enhancing Healthcare Team Outcomes

SDS is a rare blood disorder associated with pancreatic insufficiency. It is best managed by an interprofessional team that includes hematology nurses. There is no cure for this disorder and treatment is required in most patients. Unfortunately, the treatments do have adverse effects that are not well tolerated. Once a diagnosis of SDS is made, a genetic consult should be made for the rest of the family, 

The outcomes for patients with SDS are guarded.



Rebecca Ward


Muhammad Aziz


7/17/2023 9:21:34 PM



Tan S, Kermasson L, Hoslin A, Jaako P, Faille A, Acevedo-Arozena A, Lengline E, Ranta D, Poirée M, Fenneteau O, Ducou le Pointe H, Fumagalli S, Beaupain B, Nitschké P, Bôle-Feysot C, de Villartay JP, Bellanné-Chantelot C, Donadieu J, Kannengiesser C, Warren AJ, Revy P. EFL1 mutations impair eIF6 release to cause Shwachman-Diamond syndrome. Blood. 2019 Jul 18:134(3):277-290. doi: 10.1182/blood.2018893404. Epub 2019 May 31     [PubMed PMID: 31151987]


Szabo CE, Man OI, Şerban RS, Kiss E, Lazăr CF. Bruising as the first sign of exocrine pancreatic insufficiency in infancy. Medicine and pharmacy reports. 2019 Apr:92(2):200-204. doi: 10.15386/mpr-1231. Epub 2019 Apr 25     [PubMed PMID: 31086851]


Jensen LT, Phyu T, Jain A, Kaewwanna C, Jensen AN. Decreased accumulation of superoxide dismutase 2 within mitochondria in the yeast model of Shwachman-Diamond syndrome. Journal of cellular biochemistry. 2019 Aug:120(8):13867-13880. doi: 10.1002/jcb.28660. Epub 2019 Apr 2     [PubMed PMID: 30938873]


Cipolli M, Tridello G, Micheletto A, Perobelli S, Pintani E, Cesaro S, Maserati E, Nicolis E, Danesino C, Italian Registry Organization. Normative growth charts for Shwachman-Diamond syndrome from Italian cohort of 0-8 years old. BMJ open. 2019 Jan 17:9(1):e022617. doi: 10.1136/bmjopen-2018-022617. Epub 2019 Jan 17     [PubMed PMID: 30782681]


Kallen ME, Dulau-Florea A, Wang W, Calvo KR. Acquired and germline predisposition to bone marrow failure: Diagnostic features and clinical implications. Seminars in hematology. 2019 Jan:56(1):69-82. doi: 10.1053/j.seminhematol.2018.05.016. Epub 2018 Jun 23     [PubMed PMID: 30573048]


Bezzerri V, Cipolli M. Shwachman-Diamond Syndrome: Molecular Mechanisms and Current Perspectives. Molecular diagnosis & therapy. 2019 Apr:23(2):281-290. doi: 10.1007/s40291-018-0368-2. Epub     [PubMed PMID: 30413969]

Level 3 (low-level) evidence


Nelson AS, Myers KC. Diagnosis, Treatment, and Molecular Pathology of Shwachman-Diamond Syndrome. Hematology/oncology clinics of North America. 2018 Aug:32(4):687-700. doi: 10.1016/j.hoc.2018.04.006. Epub 2018 Jun 5     [PubMed PMID: 30047420]


Ong SY, Li ST, Wong GC, Ho AYL, Nagarajan C, Ngeow J. Delayed diagnosis of Shwachman diamond syndrome with short telomeres and a review of cases in Asia. Leukemia research reports. 2018:9():54-57. doi: 10.1016/j.lrr.2018.04.002. Epub 2018 Apr 9     [PubMed PMID: 29892551]

Level 3 (low-level) evidence


Farooqui SM, Ward R, Aziz M. Shwachman-Diamond Syndrome. StatPearls. 2023 Jan:():     [PubMed PMID: 29939643]


Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, Nelson A, Myers K. Shwachman-Diamond Syndrome. GeneReviews(®). 1993:():     [PubMed PMID: 20301722]