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.
-
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]
-
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.
-
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]
Procedures
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
See the list below:
-
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.
Staging
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
-
Autosomal recessive inheritance.
