Background Shwachman-Diamond Syndrome (SDS) is a multisystem disorder characterized by exocrine pancreatic insufficiency and bone marrow failure with a variable clinical phenotype and an increased risk for secondary hematological malignancy. With evolving therapies, optimized management and monitoring, patients are aging and reaching adulthood.

Methods We have analyzed clinical data of 36 adult patients diagnosed with SDS from Germany collected by the Severe Chronic Neutropenia International Registry (SCNIR). In addition, a survey on quality of life was initiated in this cohort, after receiving approval from the ethic committee of the Medical School in Hannover.

Results The SCNIR has collected data on 76 German patients with the clinical diagnosis of SDS. Until today 36 patients of the German cohort have reached adulthood according to their date of birth.

Patients' characteristics: 36 SDS patients (15 female, 21 male) including four families with two affected siblings. The median age at clinical SDS diagnosis was 2.49 years (range 0- 23.62 years). Genetic testing for SBDS gene mutations has been performed in 35 patients, identifying SBDS mutations in 97% of patients tested. The majority of patients harbors the common compound heterozygous SBDS mutations c.258+2T>C + c.183_184TA>CT.

Exocrine pancreatic insufficiency was reported at registration in 65% of patients. Neutropenia was the most common hematological finding in first reported CBCs. Besides infections variable co-morbidities have been reported in the course of the disease as well as behavioral issues and impaired socialization skills.

Two life births have been reported both from two 25-year-old mothers.

One patient has developed myelodysplastic syndrome (MDS), 2 patients have developed acute myeloid leukemia (AML) and one patient has developed pancytopenia in adulthood. Three of the four patients underwent hematopoietic cell transplantation (HCT) at the age of 23, 26 and 30 years. Only one patient survived after HCT in adulthood. The cohort includes 6 additional long-term survivors after HCT in childhood (out of 10 HCTs performed in childhood) resulting in long-term survivors comprising 20% of the total cohort.

A total of three patients has died in adulthood at 26, 36 and 45 years of age. Causes of death in adults were MDS (n=1) and transplant related mortality (n=2).

A survey on quality of life was sent to all patients alive (n=33). The survey was undeliverable to six patients due to outdated contact information or relocation of the patient abroad. Of the remaining patients, fifteen have to date completed and returned the questionnaire. Eight of the participants indicated living independently, outside of the parental household while the remainder continue to rely on parental support with a small proportion requiring complete care support due to the degree of physical or mental disability. Thirteen (87%) participants had obtained a secondary school diploma. Five patients successfully completed a vocational qualification and three patients are pursuing a university degree while other patients are unable to successfully complete their vocational training. Lack of motivation, tension, worry, anxiety, and concentration difficulties as well as vulnerability are the most common problems reported. In self-assessment, 73% of patients reported being in good or very good health and are moderately satisfied with their life. Although most patients maintain continuous medical care, specialist hematological management is not consistently implemented despite the predominance of hematological complications.

Conclusion Shwachman-Diamond Syndrome remains a complex multisystem disorder with persistent challenges extending into adulthood. A proportion of adult patients are unable to live independently and continue to rely on parental or familial support. While the majority of individuals attain a secondary school diploma, not all are able to pursue or complete higher education, possibly due to limited resilience. Hematological complications, particularly MDS and AML, continue to represent the primary life-limiting factors. Among adults with SDS, approximately one in five has undergone HCT. Consequently, lifelong hematological surveillance, including molecular genetic testing for leukemia-associated mutations, remains crucial, even in the presence of stable blood counts. Multidisciplinary care should be continued into adulthood to adequately manage the complexity of the disease.

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2025
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