From the Research
Adults with Schwachman-Diamond Syndrome (SDS) require multidisciplinary management to address the spectrum of clinical manifestations, including pancreatic insufficiency, bone marrow dysfunction, and skeletal abnormalities, with a focus on preventing morbidity, mortality, and improving quality of life. The primary manifestations of SDS in adults include pancreatic insufficiency causing malabsorption and malnutrition, bone marrow dysfunction leading to cytopenias (particularly neutropenia), and skeletal abnormalities. Adults with SDS often experience recurrent infections, gastrointestinal symptoms, and are at increased risk for myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) 1.
Clinical Manifestations
The clinical manifestations of SDS involve multiple organ systems, including:
- Bone marrow dysfunction leading to cytopenias, particularly neutropenia
- Exocrine pancreatic insufficiency leading to malabsorption and malnutrition
- Skeletal abnormalities
- Neurocognitive, dermatologic, and retinal changes may also be found 1
Management Strategies
Management strategies for SDS focus on addressing these specific complications, including:
- Pancreatic enzyme replacement therapy (PERT) with typical dosing of 500-2,500 lipase units/kg/meal, adjusted based on symptoms and nutritional status
- Nutritional support with fat-soluble vitamin supplementation (vitamins A, D, E, and K) and high-calorie diets
- For neutropenia, granulocyte colony-stimulating factor (G-CSF) may be administered at 5-10 μg/kg/day subcutaneously, titrated to maintain absolute neutrophil counts above 1,000/μL
- Prophylactic antibiotics are sometimes used during severe neutropenic periods
- Regular monitoring is crucial, including complete blood counts every 3-6 months, annual bone marrow examinations to screen for MDS/AML, and periodic pancreatic function tests 2, 3
Individualized Approach
The management approach must be individualized as SDS severity varies significantly between patients, with treatment decisions based on the specific manifestations and their severity in each individual. Genetic counseling is important for family planning, and orthopedic complications may require surgical intervention 4, 5.
Recent Insights
Recent studies have provided insights into the genetic and biochemical aspects of SDS, including the identification of pathogenic variants in genes such as SBDS, DNAJC21, EFL1, and SRP54, which are involved in ribosome biogenesis or early protein synthesis 1. These findings highlight the importance of a comprehensive approach to managing SDS, taking into account the complex interplay of genetic, biochemical, and clinical factors.