Shwachman-Diamond Syndrome Workup

Updated: Sep 09, 2022
  • Author: Antoinette C Spoto-Cannons, MD, FAAP; Chief Editor: Hassan M Yaish, MD  more...
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Laboratory Studies

See the list below:

  • CBC to assess neutropenia, anemia, and thrombocytopenia

    • Cyclic or persistent neutropenia is observed in 88-100% of patients with Shwachman-Diamond syndrome (SDS). [61, 62, 63, 6, 64, 52] Because the neutropenia may be intermittent, CBC counts may need to be repeated biweekly over a 3-week period to document neutropenia. [65]

      • Neutropenia is defined as an absolute neutrophil count (ANC) of less than 1500/mcL in whites and less than 1200 in blacks. See the Absolute Neutrophil Count calculator.

      • 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.

    • A CBC count should also be obtained every 3-6 months or as clinically indicated. [66]

  • Neutrophil function studies: A neutrophil migration defect may be documented.

  • Fetal hemoglobin: This is elevated in approximately 80% of patients with Shwachman-Diamond syndrome. [31]

  • Iron, folate, and vitamin B12 levels: Patients may have associated iron, folate, or vitamin B12 deficiency secondary to malabsorption. Obtain at time of diagnosis and as clinically indicated. [66]

  • 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. [67] 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. [10]

  • 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. [5] Obtain at time of diagnosis and as clinically indicated. [66]

  • 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. [68, 69] The test should be repeated if there is any doubt regarding the diagnosis. [69]

  • 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. [70]

    • 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.

    • These should be obtained at time of diagnosis and as clinically indicated. [66]

  • Immunoglobulin levels: Immunoglobulin A (IgA), IgM, and/or immunoglobulin G (IgG) levels may be low. Obtain at time of diagnosis and as clinically indicated. [66]

  • Growth hormone levels: These are often decreased in persons with Shwachman-Diamond syndrome.

  • Vitamin A, D, E and K levels: These may be low due to malabsorption. [63] Obtain vitamin A, D, and E and prothrombin time at time of diagnosis, one month after initiation of pancreatic enzyme therapy, then every 6-12 months. [66]

  • 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. [71]

CT scanning reveals lipomatosis of the pancreas. The size of the pancreas may be normal or atrophic. [72]

MRI may be used to evaluate the pancreatic fat content and can even help confirm the clinical diagnosis of Shwachman-Diamond syndrome. [73] 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. [74]

A skeletal survey in a person with Shwachman-Diamond syndrome may reveal some of the following skeletal abnormalities:

  • Delayed bone age (>75%). [5]

  • 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%) [67] and have been reported to cause respiratory failure in newborns.

  • 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%). [75]

  • Abnormal tubulation of the long bones, especially the ulnae, tibia, and first metacarpals (33%). [68, 5]

  • Valgus deformities of the elbows and knees. [68]

  • Slipped femoral epiphysis [76]

  • Kyphosis and scoliosis [76]

  • Osteopenia early on, which improves with age. As many as 45% of patients who become pancreatic sufficient later in childhood have shown complete reversal. However, adults should be screened with densitometry. [66]

MRI of the brain reveals as much as a 23% reduction in overall gray-matter and white-matter volume with resultant increase in ventricular volume when compared with persons without Shwachman-Diamond syndrome. The areas of the brain most affected include the corpus callosum, brain stem, cerebellum, and thalamus. Booij et al's findings indicate that patients with Shwachman-Diamond may have a dysregulated dopaminergic system that can account for ADHD and learning difficulties. [77]

Patients with Shwachman-Diamond syndrome may show diastolic dysfunction at rest and depressed left ventricular contractility during stress on MRI of the heart. [78]


Other Tests

See the list below:

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

    • Isochromosome arm 7q may be a specific marker of myeloid malignant transformation.

    • Bone marrow aspiration and biopsy are indicated at the time of diagnosis and every 1-3 years or as clinically indicated. [79, 41, 66]

  • Diagnosis is confirmed by performing genetic testing for the SBDS gene located on chromosome 7q11, which is present in 90% of patients with Shwachman-Diamond syndrome.

  • Developmental/neuropsychological screening due to risk for developmental delay, ADHD, and autism spectrum disorders. Obtain at time of diagnosis with regular assessment at well child visits with special attention at age 6-8 years, age 11-13 years, and age 15-17 years. [66]



See the list below:

  • Duodenal aspiration (performed by a gastroenterologist) in the person with Shwachman-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

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  • Biopsy of the pancreas of a person with Shwachman-Diamond syndrome reveals mostly adipose tissue containing the islets of Langerhans with very few elements of exocrine gland structure present. [44] The pancreas of patients with cystic fibrosis usually has fibrosis rather than lipomatosis, as is observed in patients with Shwachman-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 Shwachman-Diamond syndrome), including acute myeloid leukemia, acute lymphoid leukemia, and juvenile chronic myeloid leukemia. However, examination of the bone marrow in a person with Shwachman-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. [44, 68]

  • The liver of an individual with Shwachman-Diamond syndrome may exhibit periportal fibrosis, [70] 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 Shwachman-Diamond syndrome.



Diagnostic criteria of Shwachman-Diamond syndrome

According to a consensus at the international conference in 2002, persons diagnosed with Shwachman-Diamond syndrome must fulfill at least two of the following criteria: [80]

  • At least 2 of the following:

    • Chronic cytopenia(s) detected on at least 2 occasions over at least 3 months

    • Reduced marrow progenitors

    • Persistent elevation of hemoglobin F

    • Persistent RBC macrocytosis (not caused by nutritional deficiency)

  • At least one of the following:

    • Evidence of pancreatic lipomatosis

    • Reduced levels of at least 2 pancreatic enzymes adjusted to age

  • Positive genetic testing

  • First degree-family member with Shwachman-Diamond syndrome