denotes an abstract that is clinically relevant.
denotes that this is a recommended PHD Trainee Session.
denotes that this is a ticketed session.Hematology Disease Topics & Pathways:
Clinical Practice (Health Services and Quality), Diseases, Myeloid Malignancies, Metabolic Disorders
Description:
Iron homeostasis and porphyrin metabolism must be closely coordinated to ensure efficient biosynthesis of heme. Disturbed coordination is exemplified by sideroblastic anemias, which are characterized by insufficient incorporation of iron into the end product of the prophyrin biosynthesis pathway, resulting in anemia and mitochondrial as well as systemic iron overload. Conversely, iron overload from other causes, like hereditary hemochromatosis, can have unfavourable effects on porphyrin synthesis, provoking porphyria cutanea tarda. The intricate interplay between iron and porphyrin metabolism can be disturbed by inherited or acquired causes. Therapeutic options to mitigate the ensuing clinical symptoms are highlighted by the three speakers of this session.
Dr. Domenico Girelli will discuss hereditary hemochromatosis according to the recent clinically oriented classification. While hyperferritinemia is common in practice, hemochromatosis accounts for few cases, typically with increased transferrin saturation. HFE-related hemochromatosis has a low penetrance, influenced by lifestyle and dysmetabolic factors. Most patients are currently identified in the early phases before life-threatening manifestations. Phlebotomy remains the mainstay for achieving iron depletion, with blood donation being an option for maintenance. The management of rare, severe non-HFE forms, requiring a comprehensive approach, will also be presented.
Dr. Norbert Gattermann will outline the pathophysiology of systemic iron overload in MDS as well as mitochondrial iron accumulation in patients with acquired sideroblastic anemias. He will explain how SF3B1 mutations and the subsequent missplicing and deficiency of ABCB7 may lead to impaired heme synthesis and excess mitochondrial iron. The rationale for iron chelation therapy in MDS will be considered, together with some of its practical aspects. Finally, Dr. Gattermann will assess the extent to which luspatercept might contribute to the management of iron overload in patients with MDS.
Dr. Rebecca Leaf will focus on porphyria cutanea tarda (PCT), a disorder of heme biosynthesis that arises due to inhibition of hepatic uroporphyrinogen decarboxylase in the setting of increased liver iron content and oxidative stress. Patients with PCT invariably have siderosis on liver biopsy and up to 20% are homozygous for the HFE C282Y mutation. PCT manifests as blistering cutaneous lesions on sun-exposed areas, skin fragility, and elevated plasma and urine porphyrins. Treatment includes therapeutic phlebotomy to decrease total body iron levels and hydroxychloroquine, which reduces hepatic porphyrin content.
Dr. Domenico Girelli will discuss hereditary hemochromatosis according to the recent clinically oriented classification. While hyperferritinemia is common in practice, hemochromatosis accounts for few cases, typically with increased transferrin saturation. HFE-related hemochromatosis has a low penetrance, influenced by lifestyle and dysmetabolic factors. Most patients are currently identified in the early phases before life-threatening manifestations. Phlebotomy remains the mainstay for achieving iron depletion, with blood donation being an option for maintenance. The management of rare, severe non-HFE forms, requiring a comprehensive approach, will also be presented.
Dr. Norbert Gattermann will outline the pathophysiology of systemic iron overload in MDS as well as mitochondrial iron accumulation in patients with acquired sideroblastic anemias. He will explain how SF3B1 mutations and the subsequent missplicing and deficiency of ABCB7 may lead to impaired heme synthesis and excess mitochondrial iron. The rationale for iron chelation therapy in MDS will be considered, together with some of its practical aspects. Finally, Dr. Gattermann will assess the extent to which luspatercept might contribute to the management of iron overload in patients with MDS.
Dr. Rebecca Leaf will focus on porphyria cutanea tarda (PCT), a disorder of heme biosynthesis that arises due to inhibition of hepatic uroporphyrinogen decarboxylase in the setting of increased liver iron content and oxidative stress. Patients with PCT invariably have siderosis on liver biopsy and up to 20% are homozygous for the HFE C282Y mutation. PCT manifests as blistering cutaneous lesions on sun-exposed areas, skin fragility, and elevated plasma and urine porphyrins. Treatment includes therapeutic phlebotomy to decrease total body iron levels and hydroxychloroquine, which reduces hepatic porphyrin content.