Congenital hemolytic anemia

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Congenital hemolytic anemia
Other namesHereditary hemolytic anemia
Specialty Hematology
Symptoms Anemia
TypesHereditary spherocytosis, Hereditary elliptocytosis, Glucose-6-phosphate dehydrogenase deficiency, Pyruvate kinase deficiency, Aldolase A deficiency, Sickle cell anemia, Congenital dyserythropoietic anemia, Thalassemia
Causes A group of inherited diseases
Diagnostic method Blood tests, genetic testing

Congenital hemolytic anemia is a diverse group of hereditary conditions marked by premature removal of red blood cells from circulation (hemolysis), often leading to severe anemia and decreased life expectancy. This may be caused by defects in the red cell's membrane proteins, internal metabolism, or by defective or deficient hemoglobin.

Contents

Subtypes

Hereditary spherocytosis

Hereditary spherocytosis is a common hemolytic disorder distinguished by a defect or deficiency within one or more of the proteins that make up the membrane of the red blood cell. As a result of this, red blood cells have an abnormal shape, require more metabolic energy, and are trapped and destroyed prematurely in the spleen. With a prevalence of about 1 in 2000, hereditary spherocytosis, including the very mild or subclinical forms, is the most prevalent cause of non-immune hemolytic anemia in people of Northern European ancestry. However, very mild varieties of the disease are likely to be far more common. In 75% of cases, hereditary spherocytosis is inherited as a dominant trait, with the remainder being truly recessive cases as well as de novo mutations. [1] The hallmark of HS is chronic hemolysis. Most people have a mild condition that does not require any treatment. In extreme situations, it causes jaundice, splenomegaly, and severe anemia. [2] Folate supplementation is advised in cases of severe and moderate HS but is not required in cases of mild HS. [3] In severe cases, splenectomy may be advised as a therapy and may help to improve the condition. [2]

Hereditary elliptocytosis

Hereditary elliptocytosis is a group of red blood cell membrane disorders characterized by elliptical erythrocytes and decreased RBC survival. Defects in the cytoskeletal proteins that keep red blood cells in their biconcave shape can cause hereditary elliptocytosis. These defects can be either in quantity or structure. Since most patients have compensated hemolysis even in the presence of hemolysis, symptoms are generally uncommon. Patients with significant clinical hemolysis, on the other hand, may experience anemia-related symptoms. Hereditary elliptocytosis is diagnosed by identifying abnormal red blood cell morphology on a peripheral blood smear and identifying characteristic membrane biomechanical properties with osmotic gradient ektacytometry. Hereditary elliptocytosis (HE) rarely causes symptoms and requires no treatment. Splenectomy significantly improves the condition of patients with clinically significant hemolytic anemia. [4]

Glucose-6-phosphate dehydrogenase deficiency

Glucose-6-phosphate dehydrogenase deficiency is the most common enzyme deficiency worldwide, [5] is an inborn error of metabolism that predisposes to red blood cell breakdown. [6] Most of the time, those who are affected have no symptoms. [7] Following a specific trigger, symptoms such as yellowish skin, dark urine, shortness of breath, and feeling tired may develop. [6] [8] Complications can include anemia and newborn jaundice. [8] The most important measure is prevention – avoidance of the drugs and foods that cause hemolysis. Vaccination against some common pathogens (e.g. hepatitis A and hepatitis B) may prevent infection-induced attacks. [9]

Pyruvate kinase deficiency

Pyruvate kinase deficiency is an inherited metabolic disorder of the enzyme pyruvate kinase which affects the survival of red blood cells. [10] [11] Both autosomal dominant and recessive inheritance have been observed with the disorder; classically, and more commonly, the inheritance is autosomal recessive. Pyruvate kinase deficiency is the second most common cause of enzyme-deficient hemolytic anemia, following G6PD deficiency. [12] The symptoms of pyruvate kinase deficiency are mild to severe hemolytic Anemia, cholecystolithiasis, tachycardia, hemochromatosis, icteric sclera, splenomegaly, leg ulcers, jaundice, fatigue, and shortness of breath. [13] The diagnosis of pyruvate kinase deficiency can be done by full blood counts (differential blood counts) and reticulocyte counts. [14] The most common treatment is blood transfusions, especially in infants and young children. This is done if the red blood cell count has fallen to a critical level. [15]

Aldolase A deficiency

Aldolase A deficiency is an autosomal recessive metabolic disorder resulting in a deficiency of the enzyme aldolase A; the enzyme is found predominantly in red blood cells and muscle tissue. The deficiency may lead to hemolytic anaemia as well as myopathy associated with exercise intolerance and rhabdomyolysis in some cases. [16]

Sickle cell anemia

The underlying cause of sickle cell anemia is a mutation of the beta-hemoglobin gene which results in an abnormal hemoglobin. Under conditions of low oxygen, dehydration, or stress the abnormal hemoglobin can polymerise: this distorts the shape of the red blood cell to form a characteristic sickle shape. [17] Sickle cell anemia symptoms usually appear around the age of six months. They can change over time and differ from person to person. A few indications and symptoms include anemia, sporadic episodes of excruciating pain, hand and foot edema, recurrent infections, delayed puberty or growth, and visual issues. [18] The goal of sickle cell anemia treatment is usually to avoid pain episodes, relieve symptoms, and prevent complications. Treatment may include infection prevention with vaccination and antibiotics, high fluid intake, folic acid supplementation, and pain medication. [19] [20] Other measures may include blood transfusion and the medication hydroxycarbamide (hydroxyurea). [20] In 2023, new gene therapies were approved involving the genetic modification and replacement of blood forming stem cells in the bone marrow. [21] [22] [23]

Congenital dyserythropoietic anemia

Congenital dyserythropoietic anemia (CDA) is a rare blood disorder, similar to the thalassemias. CDA is one of many types of anemia, characterized by ineffective erythropoiesis, and resulting from a decrease in the number of red blood cells (RBCs) in the body and a less than normal quantity of hemoglobin in the blood. [24] The symptoms and signs of congenital dyserythropoietic anemia are consistent fatigue, weakness, and pale skin. [24] The diagnosis of congenital dyserythropoietic anemia can be done via sequence analysis of the entire coding region, types I, [25] II, [26] III [27] and IV. Treatment of individuals with CDA usually consist of frequent blood transfusions, but this can vary depending on the type that the individual has. [28]

Thalassemia

Thalassemia is a group of inherited anemias in which hemoglobin synthesis is reduced from normal levels, or sometimes zero. [29] Symptoms depend on the extent to which hemoglobin production is affected, and can vary from none to severe. Often there is mild to severe anemia (low red blood cells or hemoglobin) as thalassemia can affect the production of red blood cells and also affect how long the red blood cells live. Symptoms of anemia include feeling tired and having pale skin. Other symptoms of thalassemia include bone problems, an enlarged spleen, yellowish skin, pulmonary hypertension, and dark urine. Slow growth may occur in children. [30] Treatment depends on the type and severity. [31] Treatment for those with more severe disease often includes regular blood transfusions, iron chelation, and folic acid. [31] Gene therapy or a bone marrow transplant are options for severe cases. [31] [32]

See also

References

  1. ↑ Iolascon, A.; Avvisati, R.A.; Piscopo, C. (2010). "Hereditary spherocytosis". Transfusion Clinique et Biologique. 17 (3). Elsevier BV: 138–142. doi:10.1016/j.tracli.2010.05.006. ISSN   1246-7820. PMID   20655264.
  2. 1 2 Shafqat, Shah; Roger, Vega (May 2004). "Hereditary Spherocytosis" . Pediatrics in Review. 25 (5): 168–172. doi:10.1542/pir.25-5-168. ISSN   0191-9601. PMID   15121908 . Retrieved 20 November 2023.
  3. ↑ Bolton-Maggs, Paula H. B.; Langer, Jacob C.; Iolascon, Achille; Tittensor, Paul; King, May-Jean (November 5, 2011). "Guidelines for the diagnosis and management of hereditary spherocytosis – 2011 update". British Journal of Haematology. 156 (1). Wiley: 37–49. doi: 10.1111/j.1365-2141.2011.08921.x . ISSN   0007-1048. PMID   22055020.
  4. ↑ Kim, Daniel J (July 31, 2023). "Hereditary Elliptocytosis: Practice Essentials, Pathophysiology, Etiology". Medscape Reference. Retrieved November 20, 2023.
  5. ↑ Frank, Jennifer E. (2005-10-01). "Diagnosis and Management of G6PD Deficiency". American Family Physician. 72 (7): 1277–1282. ISSN   0002-838X. PMID   16225031.
  6. 1 2 "Glucose-6-phosphate dehydrogenase deficiency". Genetics Home Reference. 6 December 2017. Retrieved 20 November 2023.
  7. ↑ "Glucose-6-phosphate dehydrogenase deficiency". Genetic and Rare Diseases Information Center (GARD). 2017. Archived from the original on 27 April 2021. Retrieved 20 November 2023.
  8. 1 2 "Glucose-6-Phosphate Dehydrogenase Deficiency". NORD (National Organization for Rare Disorders). 2017. Retrieved 20 November 2023.
  9. ↑ Monga A, Makkar RP, Arora A, Mukhopadhyay S, Gupta AK (July 2003). "Case report: Acute hepatitis E infection with coexistent glucose-6-phosphate dehydrogenase deficiency". Can J Infect Dis. 14 (4): 230–1. doi: 10.1155/2003/913679 . PMC   2094938 . PMID   18159462.
  10. ↑ "Pyruvate kinase deficiency: MedlinePlus Medical Encyclopedia". www.nlm.nih.gov. Retrieved 2023-11-20.
  11. ↑ "Pyruvate kinase deficiency | Disease | Overview | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Archived from the original on 2015-09-05. Retrieved 2023-11-20.
  12. ↑ Gallagher, Patrick G.; Glader, Bertil (2016-05-01). "Diagnosis of Pyruvate Kinase Deficiency". Pediatric Blood & Cancer. 63 (5): 771–772. doi:10.1002/pbc.25922. ISSN   1545-5017. PMID   26836632. S2CID   42964783.
  13. ↑ "Pyruvate Kinase Deficiency Clinical Presentation: History and Physical Examination". emedicine.medscape.com. Retrieved 2023-11-20.
  14. ↑ Disorders, National Organization for Rare (2003-01-01). NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. p. 496. ISBN   9780781730631.
  15. ↑ Zanella, A.; Bianchi, P.; Fermo, E. (2007-06-01). "Pyruvate kinase deficiency". Haematologica. 92 (6): 721–723. doi: 10.3324/haematol.11469 . ISSN   0390-6078. PMID   17550841.
  16. ↑ Kishi H, Mukai T, Hirono A, Fujii H, Miwa S, Hori K (1987). "Human aldolase A deficiency associated with a hemolytic anemia: Thermolabile aldolase due to a single base mutation". Proc. Natl. Acad. Sci. 84 (23): 8623–7. Bibcode:1987PNAS...84.8623K. doi: 10.1073/pnas.84.23.8623 . PMC   299598 . PMID   2825199.
  17. ↑ "Sickle Cell Disease". medlineplus.gov. Retrieved 2025-09-19.
  18. ↑ "Sickle cell anemia-Sickle cell anemia". Mayo Clinic. March 9, 2022. Retrieved November 20, 2023.
  19. ↑ "Sickle-cell disease and other haemoglobin disorders Fact sheet N°308". January 2011. Archived from the original on 9 March 2016. Retrieved 8 March 2016.
  20. 1 2 "Sickle Cell Disease - Treatment". National Heart, Lung, and Blood Institute. 30 September 2024. Retrieved 26 October 2024.
  21. ↑ "FDA Approves First Gene Therapies to Treat Patients with Sickle Cell Disease". U.S. Food and Drug Administration (FDA). 8 December 2023. Archived from the original on 8 December 2023. Retrieved 8 December 2023.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  22. ↑ Wilkinson, Emma (16 November 2023). "UK regulator approves "groundbreaking" gene treatment for sickle cell and β thalassaemia" . BMJ. 383: 2706. doi:10.1136/bmj.p2706. ISSN   1756-1833. PMID   37973171. S2CID   265264939.
  23. ↑ Singh, Ajeet; Irfan, Hamza; Fatima, Eeshal; Nazir, Zainab; Verma, Amogh; Akilimali, Aymar (2024-05-15). "Revolutionary breakthrough: FDA approves CASGEVY, the first CRISPR/Cas9 gene therapy for sickle cell disease". Annals of Medicine and Surgery. 86 (8): 4555–4559. doi:10.1097/MS9.0000000000002146. PMC   11305803 . PMID   39118728.
  24. 1 2 "CDA". Genetics Home Reference. 2016-01-25. Retrieved 2023-11-20.
  25. ↑ "Congenital dyserythropoietic anemia, type I — Conditions — GTR — NCBI". www.ncbi.nlm.nih.gov. Retrieved 2023-11-20.
  26. ↑ "Congenital dyserythropoietic anemia, type II — Conditions — GTR — NCBI". www.ncbi.nlm.nih.gov. Retrieved 2023-11-20.
  27. ↑ "Congenital dyserythropoietic anemia, type III — Conditions — GTR — NCBI". www.ncbi.nlm.nih.gov. Retrieved 2023-11-20.
  28. ↑ Greer, John P.; Arber, Daniel A.; Glader, Bertil; List, Alan F.; Means, Robert T.; Paraskevas, Frixos; Rodgers, George M. (2013-08-29). Wintrobe's Clinical Hematology. Lippincott Williams & Wilkins. p. 994. ISBN   9781469846224.
  29. ↑ "Thalassemia - What Is Thalassemia? | NHLBI, NIH". www.nhlbi.nih.gov. 2022-05-31. Retrieved 2025-09-19.
  30. ↑ "What Are the Signs and Symptoms of Thalassemias?". NHLBI. 3 July 2012. Archived from the original on 16 September 2016. Retrieved 5 September 2016.
  31. 1 2 3 "How Are Thalassemias Treated?". NHLBI. 3 July 2012. Archived from the original on 16 September 2016. Retrieved 5 September 2016.
  32. ↑ Commissioner, Office of the (16 January 2024). "FDA Roundup: January 16, 2024". FDA. Archived from the original on 16 January 2024. Retrieved 19 January 2024.

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