Sideroblastic anemia is due to the abnormal use of iron during erythropoiesis and is defined by the presence of ring sideroblasts in the bone marrow. It can be inherited, caused by a mutation of genes involved in heme synthesis, or acquired. Acquired forms can be either primary, such as those associated with myelodysplastic syndromes, or secondary caused by chemical influence or neoplasms.19
Inherited forms with single enzyme deficiencies have been identified for:
- ALA synthase
- PBG deaminase
- Uroporphyrinogen III synthase
- Uroporphyrinogen decarboxylase
- Coproporphyrinogen oxidase
- Protoporphrinogen oxidase
- Ferrochelatase
Porphyrias are usually inherited conditions associated with skin and nervous system disorders but can be acquired. The word is most often associated with inherited conditions that impair the production of protoporphyrin.
6 They can be classified into two major categories: acute and cutaneous.
20 Three forms of inherited porphyria, found in the cutaneous porphyria classification, have been associated with hematologic manifestations and have genetic deficiencies of the following enzymes:
- Uroporphyrinogen III synthase (Congenital Erythropoietic Porphyria (CEP))
- Ferrochelatase (Erythropoietic Protoporphyria (EPP))
- ALA-synthase 2 (X-linked Erythropoietic Protoporphyria (XLEPP))
Of these inherited deficiencies, only XLEPP is X-linked while EPP and CEP are both autosomal dominant.
6 The absence or abnormalities of the heme pathway enzymes cause an accumulation of the products from earlier stages in the pathway in erythrocytes and hepatocytes. These products are released from the cells as they age or die and are then excreted in the urine or feces. Analysis of products found in the red blood cells, urine, or feces aids in diagnosis through laboratory findings. Unlike the sideroblastic anemia described above, very rare examples of porphyrias have presented with ring sideroblasts.
For the three forms of porphyria that impact hematologic conditions, patients may exhibit photosensitivity, possibly resulting in severe burns when exposed to sunlight. There are several hypotheses that the buildup of free intermediate products can lead to psychosis. In addition, particularly related to congenital erythropoietic porphyria (CEP), also known as Gunther's disease, there are several findings that have resulted in the myths that these individuals are vampires.18 For example, individuals with CEP may have an aversion to garlic because certain compounds degrade heme oxygenase exacerbating anemia. Scarring and deformities in sun-exposed areas, as well as a build-up of toxic porphyrins in bone and teeth that fluoresce in UV light, contribute to the myth. However, contrary to the myths, it was found that the craving for blood was not generally a finding in porphyria patients.6,18
6. Keohane, E. M., Otto, C.N., Walenga, J. M. (2016). Rodak's Hematology Clinical Principles and Applications. St. Louis., Elsevier, 6th Edition.18. Maas, R.P.P.W.M., Voets, P.J.G.M. "The vampire in medical perspective: myth or malady?" QJM: An International Journal of Medicine, Volume 107, Issue 11, November 2014, Pages 945–946, https://doi.org/10.1093/qjmed/hcu159.19. Ashorobi D, Chhabra A. "Sideroblastic Anemia." [Updated 2023 Jul 17]. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK538287.20. American Porphyria Foundation. "Types of Porphyria." APF. Available from: https://porphyriafoundation.org/for-patients/types-of-porphyria/.
