Primary Cause of Death in Dyskeratosis Congenita
Bone marrow failure is the leading cause of death in patients with dyskeratosis congenita (DC). 1, 2, 3
Understanding the Mortality Landscape
The mortality profile in DC is dominated by hematologic complications, though the picture becomes more complex after certain interventions:
Primary Causes of Death
- Bone marrow failure represents the principal cause of premature mortality in DC patients, occurring as the natural progression of the disease 1, 2, 3
- Pulmonary complications emerge as a major cause of death, particularly pulmonary fibrosis, which may manifest in late adolescence or early adulthood 1
- Malignant transformation contributes to mortality, with increased risk of myelodysplastic syndrome (MDS), leukemia, and head and neck squamous cell carcinoma 1, 2
Post-Transplant Mortality Patterns
When patients undergo hematopoietic stem cell transplantation (HSCT) for bone marrow failure, the mortality landscape shifts significantly:
- Pulmonary disease becomes the leading cause of death post-HSCT, with only 4 of 15 patients surviving after developing pulmonary complications following transplantation 4
- Infection represents another major cause of post-HSCT mortality 4
- Graft failure contributes to poor outcomes after transplantation 4
- Overall survival after HSCT remains poor, with 5-year survival of only 57-70% and 10-year survival of just 23-28% 4
Clinical Context and Pathophysiology
The high mortality from bone marrow failure reflects the fundamental pathophysiology of DC as a telomere maintenance disorder:
- All DC patients have telomeres below the first percentile for age, leading to progressive hematopoietic failure 1, 2, 3
- The bone marrow failure typically manifests as progressive pancytopenia affecting multiple cell lines 1, 5
- This creates vulnerability to life-threatening infections and bleeding complications even before other organ systems become critically affected 1
Important Clinical Pitfalls
The prognosis after pulmonary disease develops is particularly grave, whether occurring naturally or post-transplant, with very limited survival 4, 6. This underscores why bone marrow failure, despite being potentially treatable with HSCT, remains the primary mortality driver—the treatment itself carries substantial pulmonary risks in this population.
The multisystem nature of DC means that while bone marrow failure is the leading cause of death, patients face competing mortality risks from pulmonary fibrosis, liver cirrhosis, and malignancy 1, 2. However, the temporal sequence typically places bone marrow failure first, making it the principal cause of premature mortality in untreated patients.