RESUMEN
Hereditary hemolytic anemia associated with pyruvate kinase deficiency is a rare hematological disorder that affects the glycolic pathway within red blood cells. The standard of care includes splenectomy, transfusions, and hematopoietic stem cell transplantation. However, these treatments can lead to common iatrogenic side effects such as infections, surgical complications, and iron overload. The novel drug therapy Mitapivat has shown promising results in terms of both efficacy and safety, but it can cause rare side effects such as fractures. In this report, we present the case of a 75-year-old female with hereditary hemolytic anemia caused by pyruvate kinase deficiency who suffered rib and vertebral body fractures after the initiation of Mitapivat. Screening for key risk factors of bone mineral disease can help identify patients who are at higher risk of developing fractures before starting therapy. In the future, gene therapy may provide an alternative treatment option for patients with hereditary hemolytic anemia with metabolic bone disorders.
RESUMEN
UV radiation resistance-associated gene (UVRAG) encodes a tumor suppressor with putative roles in autophagy, endocytic trafficking, and DNA damage repair but its in vivo role in T cells is unknown. Because conditional homozygous deletion of Uvrag in mice results in early embryonic lethality, we generated T-cell-specific UVRAG-deficient mice that lacked UVRAG expression specifically in T cells. This loss of UVRAG led to defects in peripheral homeostasis that could not be explained by the increased sensitivity to cell death and impaired proliferation observed for other autophagy-related gene knockout mice. Instead, UVRAG-deficient T-cells exhibited normal mitochondrial clearance and activation-induced autophagy, suggesting that UVRAG has an autophagy-independent role that is critical for peripheral naive T-cell homeostatic proliferation. In vivo, T-cell-specific loss of UVRAG dampened CD8(+) T-cell responses to LCMV infection in mice, delayed viral clearance, and impaired memory T-cell generation. Our data provide novel insights into the control of autophagy in T cells and identify UVRAG as a new regulator of naïve peripheral T-cell homeostasis.
