eMedicine Specialties > Pediatrics: General Medicine > Hematology

Shwachman-Diamond Syndrome: Differential Diagnoses & Workup

Author: Antoinette C Spoto-Cannons, MD, FAAP, Associate Professor, Department of Pediatrics, Director, Undergraduate Children's Health Care Education, University of South Florida College of Medicine
Coauthor(s): Jessica Marie Keshishian, MD, Resident Physician, Department of Pediatrics, University of South Florida; Sarah Syed, University of South Florida College of Medicine; Mudra Kumar, MD, MBBS, MRCP, Associate Professor, Department of Pediatrics, University of South Florida College of Medicine
Contributor Information and Disclosures

Updated: Sep 30, 2009

Differential Diagnoses

Cystic Fibrosis
Jeune Syndrome
Pearson Syndrome
Severe Combined Immunodeficiency
Thrombocytopenia-Absent Radius Syndrome

Other Problems to Be Considered

Johanson-Blizzard syndrome
Exocrine pancreatic dysfunction with refractory sideroblastic anemia
Pancreatic agenesis
Congenital rubella with chronic pancreatic insufficiency
Isolated enzyme deficiencies (eg, lipase, lipase/colipase, colipase, trypsin, amylase)
Myelokathexis
Chédiak-Higashi syndrome
Inborn errors of metabolism
Immunologic disorders (eg, hyper–immunoglobulin M [IgM] syndrome)
Congenital aplastic anemias (eg, Fanconi anemia, congenital dyskeratosis, amegakaryocytic purpura, reticular dysgenesis, several congenital neutropenia)
Dubowitz syndrome
Cartilage-Hair Hypoplasia

Workup

Laboratory Studies

  • CBC count to assess neutropenia, anemia, and thrombocytopenia
    • Cyclic or persistent neutropenia is observed in 88-95% of patients with Shwachman-Diamond syndrome (SDS). Because the neutropenia may be intermittent, CBC counts may need to be repeated biweekly over a 3-week period to document neutropenia.35
      • Neutropenia is defined as an absolute neutrophil count (ANC) of less than 1500/mcL in whites and less than 1200 in blacks.
      • Mild neutropenia is defined as an ANC of 1000-1500/mcL.
      • Moderate neutropenia is defined as an ANC of 500-1000/mcL.
      • Severe neutropenia is defined as an ANC of less than 500/mcL.
    • Anemia is present in more than 50% of patients with Shwachman-Diamond syndrome secondary to iron deficiency and/or bone marrow hypoplasia.
    • Thrombocytopenia is present in more than 25% of patients with Shwachman-Diamond syndrome.
  • Neutrophil function studies: A neutrophil migration defect may be documented.
  • Fetal hemoglobin: This is elevated in approximately 80% of patients with Shwachman-Diamond syndrome.11
  • Iron studies: Patients may have associated iron deficiency secondary to malabsorption.
  • A 72-hour fecal fat measurement:
    • An increase in fecal lipids and fatty acids is present in persons with Shwachman-Diamond syndrome.
    • The fecal fat losses vary from 3-60%, and these losses decrease with age. After an individual with Shwachman-Diamond syndrome is aged 8 years, fecal fat losses average 8% of intake.36 This decrease in fecal fat losses may be related to the patient's increasing pancreatic secretion of lipase coupled with the decreased dietary fat with age.
    • The absence of steatorrhea does not exclude the diagnosis of Shwachman-Diamond syndrome.25
  • Secretin-cholecystokinin quantitative stimulation test: Pancreatic insufficiency is evidenced by the absence or decrease of trypsin, lipase, colipase, and amylase activities in pancreatic secretions from less than 2% to approximately 10-14% of the reference range after quantitative stimulation test with intravenous secretin and cholecystokinin.21
  • Sweat test: In individuals with Shwachman-Diamond syndrome, this test demonstrates no increase in chloride, in contrast to cystic fibrosis, in which the chloride level is abnormally elevated; however, false positives have been reported.37,38 The test should be repeated if there is any doubt regarding the diagnosis.38
  • Glucose tolerance test: These findings are generally normal. Rarely, patients with Shwachman-Diamond syndrome may have diabetes mellitus.
  • Urinalysis: In persons with Shwachman-Diamond syndrome, urinalysis reveals inconsistent galactosuria with the presence of reducing substances but without glucosuria.
  • Serum bicarbonate, PCO2, hydrogen ion concentration (H+), and urinary pH: Measured simultaneously, these may suggest renal tubular acidosis.
  • Liver function tests
    • Transaminases (ie, alanine aminotransferase, aspartate aminotransferase) may be elevated in individuals with Shwachman-Diamond syndrome.39
    • Alkaline phosphatase may be within the reference range or slightly increased.
    • Findings on coagulation studies are normal, and the serum bilirubin level is within the reference range.
    • Hypoalbuminemia may be present secondary to malabsorption.
  • Immunoglobulin levels: Immunoglobulin A (IgA), IgM, and/or immunoglobulin G (IgG) levels may be low.
  • Growth hormone levels: These are often decreased in persons with Shwachman-Diamond syndrome.
  • Serum calcium and phosphorous: These levels are within the reference range.

Imaging Studies

  • The pancreas can be evaluated using ultrasonography, CT, or MRI.
    • Ultrasonographic findings of the pancreas of an individual with Shwachman-Diamond syndrome reveal increased echogenicity of the pancreatic silhouette.40
    • CT scanning reveals lipomatosis of the pancreas. The size of the pancreas may be normal or atrophic.41
    • MRI may be used to evaluate the pancreatic fat content and can even help confirm the clinical diagnosis of Shwachman-Diamond syndrome.42 In those who have mutations in the SBDS gene, MRI reveals a characteristic pattern of fat-replaced pancreas, which can differentiate these patients from patients without mutations.43
  • A skeletal survey in a person with Shwachman-Diamond syndrome may reveal some of the following skeletal abnormalities:
    • Delayed bone age (>75%)21
    • Thoracic dysostosis consisting of costochondral thickening, short flaring lower ribs, and a narrow thoracic cage that is most obvious when the individual with Shwachman-Diamond syndrome is younger than 2 years (44-60%)36
    • Metaphyseal chondrodysplasia noted in individuals with Shwachman-Diamond syndrome who are older than 6 years, as evidenced by shortening of the extremities, metaphyseal widening, and "cup" deformity of the ribs (40-80%)44
    • Abnormal tubulation of the long bones, especially the ulnae, tibia, and first metacarpals (33%)37,21
    • Valgus deformities of the elbows and knees37
    • Osteopenia early on, which improves with age (As many as 45% of patients who become pancreatic sufficient later in childhood have shown complete reversal.)

Other Tests

A predilection for developing bone marrow failure and leukemic transformation is associated with Schwachman-Diamond syndrome.

  • Isochromosome arm 7q may be a specific marker of myeloid malignant transformation.
  • As many as 90% of patients with Schwachman-Diamond syndrome have mutations in the SBDS gene on chromosome 7q11.
  • Annual bone marrow evaluation with cytogenetics may be helpful.45,18

Procedures

  • Duodenal aspiration (performed by a gastroenterologist) in the person with Schwachman-Diamond syndrome reveals a concentration of ductal (bicarbonate) secretions that is within the reference range with significant impairment of acinar (enzyme) secretions without satisfactory response to pancreatic stimulation.

Histologic Findings

  • Biopsy of the pancreas of a person with Schwachman-Diamond syndrome reveals mostly adipose tissue containing the islets of Langerhans with very few elements of exocrine gland structure present.23 The pancreas of patients with cystic fibrosis usually has fibrosis rather than lipomatosis, as is observed in patients with Schwachman-Diamond syndrome and Johanson-Blizzard syndrome. Routine biopsy of the pancreas is not indicated.
  • Periodically perform bone marrow evaluation studies because of the predilection for developing marrow failure and leukemic transformation (5-33% of patients with Schwachman-Diamond syndrome), including acute myeloid leukemia, acute lymphoid leukemia, and juvenile chronic myeloid leukemia. However, examination of the bone marrow in a person with Schwachman-Diamond syndrome typically reveals hypocellularity, with maturation arrest in the myeloid series and fat infiltration. Megakaryocytes may be within the reference range or decreased in number.23,37
  • The liver of an individual with Schwachman-Diamond syndrome may exhibit periportal fibrosis,39 periportal mononuclear infiltrate, and fibrous bridging between the portal tract areas. Cirrhosis and steatosis have been reported.
  • Endocardial fibrosis may be exhibited in the heart of a person with Schwachman-Diamond syndrome.

More on Shwachman-Diamond Syndrome

Overview: Shwachman-Diamond Syndrome
Differential Diagnoses & Workup: Shwachman-Diamond Syndrome
Treatment & Medication: Shwachman-Diamond Syndrome
Follow-up: Shwachman-Diamond Syndrome
Multimedia: Shwachman-Diamond Syndrome
References
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Further Reading

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Keywords

Shwachman-Diamond syndrome, SDS, bone marrow dysfunction, pancreatic insufficiency, short stature, congenital lipomatosis of pancreas, metaphyseal dysplasia, pancreatic hypoplasia, marrow dysfunction, pancreatic hypoplasia, marrow dysfunction, metaphyseal dysplasia, Shwachman-Bodian syndrome, Shwachman-Diamond-Oski-Knaw syndrome, cystic fibrosis, Fanconi anemia, Blackfan-Diamond, skeletal dysplasia, osteoporosis, upper respiratory tract infections, otitis media, sinusitis, pneumonia, aphthous stomatitis, skin infections, paronychia, osteomyelitis, bacteremia, myelodysplastic syndrome, MDS, leukemia, malabsorption, imperforate anus, Hirschsprung disease, constipation, diarrhea, hearing loss, tooth enamel defects, hypomaturation, hypocalcification, hypoplasia, treatment, diagnosis

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Contributor Information and Disclosures

Author

Antoinette C Spoto-Cannons, MD, FAAP, Associate Professor, Department of Pediatrics, Director, Undergraduate Children's Health Care Education, University of South Florida College of Medicine
Antoinette C Spoto-Cannons, MD, FAAP is a member of the following medical societies: American Academy of Pediatrics, Council on Medical Student Education in Pediatrics, and Florida Pediatric Society
Disclosure: Nothing to disclose.

Coauthor(s)

Jessica Marie Keshishian, MD, Resident Physician, Department of Pediatrics, University of South Florida
Jessica Marie Keshishian, MD is a member of the following medical societies: Alpha Omega Alpha, American Medical Student Association/Foundation, and Christian Medical & Dental Society
Disclosure: Nothing to disclose.

Sarah Syed, University of South Florida College of Medicine
Sarah Syed is a member of the following medical societies: American Medical Student Association/Foundation
Disclosure: Nothing to disclose.

Mudra Kumar, MD, MBBS, MRCP, Associate Professor, Department of Pediatrics, University of South Florida College of Medicine
Mudra Kumar, MD, MBBS, MRCP is a member of the following medical societies: American Academy of Pediatrics and American Society of Hematology
Disclosure: Nothing to disclose.

Medical Editor

Sharada A Sarnaik, MBBS, Professor of Pediatrics, Wayne State University School of Medicine; Director, Sickle Cell Center, Attending Hematologist/Oncologist, Children's Hospital of Michigan
Sharada A Sarnaik, MBBS is a member of the following medical societies: American Association of Blood Banks, American Association of University Professors, American Society of Hematology, American Society of Pediatric Hematology/Oncology, New York Academy of Sciences, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

James L Harper, MD, Associate Professor, Department of Pediatrics, Division of Hematology/Oncology and Bone Marrow Transplantation, Associate Chairman for Education, Department of Pediatrics, University of Nebraska Medical Center; Assistant Clinical Professor, Department of Pediatrics, Creighton University; Director, Continuing Medical Education, Children's Memorial Hospital; Pediatric Director, Nebraska Regional Hemophilia Treatment Center
James L Harper, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Research, American Federation for Clinical Research, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Council on Medical Student Education in Pediatrics, and Hemophilia and Thrombosis Research Society
Disclosure: Nothing to disclose.

CME Editor

Helen SL Chan, MBBS, FRCP(C), FAAP, Senior Scientist, Research Institute; Professor, Division of Hematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Canada
Helen SL Chan, MBBS, FRCP(C), FAAP is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Research, American Society of Hematology, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

Chief Editor

Max J Coppes, MD, PhD, MBA, Senior Vice President, Children's National Medical Center (Center for Cancer and Blood Disorders); Director, Center for Cancer and Immunology Research, Children's Research Institute, Children's National Medical Center; Professor of Medicine, Oncology, and Pediatrics, Georgetown University
Max J Coppes, MD, PhD, MBA is a member of the following medical societies: American Association for Cancer Research, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

 
 
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