Congenital hemolytic anemia

Medical condition

Congenital hemolytic anemia

Other names| Hereditary hemolytic anemia
Specialty| Hematology

Congenital hemolytic anemia (CHA) is a diverse group of rare hereditary conditions marked by decreased life expectancy and premature removal of erythrocytes from blood flow. Defects in erythrocyte membrane proteins and red cell enzyme metabolism, as well as changes at the level of erythrocyte precursors, lead to impaired bone marrow erythropoiesis. CHA is distinguished by variable anemia, chronic extravascular hemolysis, decreased erythrocyte life span, splenomegaly, jaundice, biliary lithiasis, and iron overload. Immune-mediated mechanisms may play a role in the pathogenesis of these uncommon diseases, despite the paucity of data regarding the immune system's involvement in CHAs.[1]

## Diagnosis

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### Hereditary spherocytosis

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Main article: 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.[2] 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.[3] Folate supplementation is advised in cases of severe and moderate HS but is not required in cases of mild HS.[4] In severe cases, splenectomy may be advised as a therapy and may help to improve the condition.[3]

### Hereditary elliptocytosis

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Main article: 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.[5]

### Glucose-6-phosphate dehydrogenase deficiency

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Main article: Glucose-6-phosphate dehydrogenase deficiency

Glucose-6-phosphate dehydrogenase deficiency is the most common enzyme deficiency worldwide,[6] is an inborn error of metabolism that predisposes to red blood cell breakdown.[7] Most of the time, those who are affected have no symptoms.[8] Following a specific trigger, symptoms such as yellowish skin, dark urine, shortness of breath, and feeling tired may develop.[7][9] Complications can include anemia and newborn jaundice.[9] 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.[10]

### Pyruvate kinase deficiency

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Main article: Pyruvate kinase deficiency

Pyruvate kinase deficiency is an inherited metabolic disorder of the enzyme pyruvate kinase which affects the survival of red blood cells.[11][12] 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.[13] 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.[14] The diagnosis of pyruvate kinase deficiency can be done by full blood counts (differential blood counts) and reticulocyte counts.[15] 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.[16]

### Aldolase A deficiency

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Main article: 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.[17]

### Sickle cell anemia

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See also: Sickle cell disease

The underlying cause of sickle cell anemia is the synthesis of aberrant hemoglobin, which attaches to other aberrant hemoglobin molecules inside the red blood cell to undergo rigid deformation.[18] 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.[19] The goal of sickle cell anemia treatment is usually to avoid pain episodes, relieve symptoms, and prevent complications. Medication and blood transfusions may be used as treatments. A stem cell transplant may be able to cure the disease in some children and teenagers. The use of hydroxyurea on a daily basis decreases the frequency of painful crises and may reduce the demand for blood transfusions and hospitalizations.[20]

### Congenital dyserythropoietic anemia

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Main article: 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.[21] The symptoms and signs of congenital dyserythropoietic anemia are consistent fatigue, weakness, and pale skin.[21] The diagnosis of congenital dyserythropoietic anemia can be done via sequence analysis of the entire coding region, types I,[22] II,[23] III[24] 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.[25]

### Thalassemia

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Main article: Thalassemia

Thalassemia is an inherited blood disorder that results in abnormal hemoglobin.[26] Symptoms depend on the type of thalassemia 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.[27] Treatment depends on the type and severity.[28] Treatment for those with more severe disease often includes regular blood transfusions, iron chelation, and folic acid.[28] Iron chelation may be done with deferoxamine, deferasirox or deferiprone.[28][29] Occasionally, a bone marrow transplant may be an option.[28]

## See also

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* Hematopoietic ulcer
* List of circulatory system conditions

## References

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1. ^ Zaninoni, Anna; Fermo, Elisa; Vercellati, Cristina; Marcello, Anna Paola; Barcellini, Wilma; Bianchi, Paola (June 23, 2020). "Congenital Hemolytic Anemias: Is There a Role for the Immune System?". Frontiers in Immunology. 11. Frontiers Media SA: 1309. doi:10.3389/fimmu.2020.01309. ISSN 1664-3224. PMC 7324678. PMID 32655575.
2. ^ 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.
3. ^ a b 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.
4. ^ 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.
5. ^ Kim, Daniel J (July 31, 2023). "Hereditary Elliptocytosis: Practice Essentials, Pathophysiology, Etiology". Medscape Reference. Retrieved November 20, 2023.
6. ^ Frank, Jennifer E. (2005-10-01). "Diagnosis and Management of G6PD Deficiency". American Family Physician. 72 (7): 1277–1282\. ISSN 0002-838X. PMID 16225031.
7. ^ a b "Glucose-6-phosphate dehydrogenase deficiency". Genetics Home Reference. 6 December 2017. Retrieved 20 November 2023.
8. ^ "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.
9. ^ a b "Glucose-6-Phosphate Dehydrogenase Deficiency". NORD (National Organization for Rare Disorders). 2017. Retrieved 20 November 2023.
10. ^ 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.
11. ^ "Pyruvate kinase deficiency: MedlinePlus Medical Encyclopedia". www.nlm.nih.gov. Retrieved 2023-11-20.
12. ^ "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.
13. ^ 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.
14. ^ "Pyruvate Kinase Deficiency Clinical Presentation: History and Physical Examination". emedicine.medscape.com. Retrieved 2023-11-20.
15. ^ Disorders, National Organization for Rare (2003-01-01). NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. p. 496\. ISBN 9780781730631.
16. ^ 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.
17. ^ 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.
18. ^ Lonergan, Gael J.; Cline, David B.; Abbondanzo, Susan L. (2001). "Sickle Cell Anemia". RadioGraphics. 21 (4). Radiological Society of North America (RSNA): 971–994\. doi:10.1148/radiographics.21.4.g01jl23971. ISSN 0271-5333. PMID 11452073.
19. ^ "Sickle cell anemia-Sickle cell anemia". Mayo Clinic. March 9, 2022. Retrieved November 20, 2023.
20. ^ "Sickle cell anemia-Sickle cell anemia". Mayo Clinic. March 9, 2022. Retrieved November 20, 2023.
21. ^ a b "CDA". Genetics Home Reference. 2016-01-25. Retrieved 2023-11-20.
22. ^ "Congenital dyserythropoietic anemia, type I — Conditions — GTR — NCBI". www.ncbi.nlm.nih.gov. Retrieved 2023-11-20.
23. ^ "Congenital dyserythropoietic anemia, type II — Conditions — GTR — NCBI". www.ncbi.nlm.nih.gov. Retrieved 2023-11-20.
24. ^ "Congenital dyserythropoietic anemia, type III — Conditions — GTR — NCBI". www.ncbi.nlm.nih.gov. Retrieved 2023-11-20.
25. ^ 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.
26. ^ "What Are Thalassemias?". NHLBI. 3 July 2012. Archived from the original on 26 August 2016. Retrieved 5 September 2016.
27. ^ "What Are the Signs and Symptoms of Thalassemias?". NHLBI. 3 July 2012. Archived from the original on 16 September 2016. Retrieved 5 September 2016.
28. ^ a b c d "How Are Thalassemias Treated?". NHLBI. 3 July 2012. Archived from the original on 16 September 2016. Retrieved 5 September 2016.
29. ^ "Iron Chelation". Retrieved 15 July 2020.

## Further reading

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* Haley, Kristina (2017). "Congenital Hemolytic Anemia". Medical Clinics of North America. 101 (2). Elsevier BV: 361–374\. doi:10.1016/j.mcna.2016.09.008. ISSN 0025-7125. PMID 28189176.
* Fattizzo, Bruno; Giannotta, Juri Alessandro; Cecchi, Nicola; Barcellini, Wilma (October 9, 2021). "Confounding factors in the diagnosis and clinical course of rare congenital hemolytic anemias". Orphanet Journal of Rare Diseases. 16 (1). Springer Science and Business Media LLC: 415. doi:10.1186/s13023-021-02036-4. hdl:2434/904967. ISSN 1750-1172. PMC 8501562. PMID 34627331.

## External links

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Classification|

* ICD-11: 3A10
* ICD-10: D58.9
* ICD-9-CM: 282.9
* MeSH: D000745
* SNOMED CT: 42601008

|

External resources|

* GARD: Congenital hemolytic anemia
* Scholia: Q5160435

* v
* t
* e

Diseases of red blood cells

| Polycythemia|

* Polycythemia vera

|

| Anemia|

| Nutritional|

* Micro-: Iron-deficiency anemia
* Plummer–Vinson syndrome

* Macro-: Megaloblastic anemia
* Pernicious anemia

|

Hemolytic
(mostly normo-)|

| Hereditary|

* enzymopathy: Glucose-6-phosphate dehydrogenase deficiency
* glycolysis
* pyruvate kinase deficiency
* triosephosphate isomerase deficiency
* hexokinase deficiency

* hemoglobinopathy: Thalassemia
* alpha
* beta
* delta
* Sickle cell disease/trait
* Hemoglobin C disease
* membrane: Hereditary spherocytosis
* Minkowski–Chauffard syndrome
* Hereditary elliptocytosis
* Southeast Asian ovalocytosis
* Hereditary stomatocytosis

|

Acquired|

| AIHA|

* Warm antibody autoimmune hemolytic anemia
* Cold agglutinin disease
* Donath–Landsteiner hemolytic anemia
* Paroxysmal cold hemoglobinuria
* Mixed autoimmune hemolytic anemia

|

* membrane
* paroxysmal nocturnal hemoglobinuria

* Microangiopathic hemolytic anemia
* Thrombotic microangiopathy
* Hemolytic–uremic syndrome

* Drug-induced autoimmune
* Drug-induced nonautoimmune

* Hemolytic disease of the newborn

Aplastic
(mostly normo-)|

* Hereditary: Fanconi anemia
* Diamond–Blackfan anemia

* Acquired: Pure red cell aplasia
* Sideroblastic anemia
* Myelophthisic

Blood tests|

* Mean corpuscular volume
* normocytic
* microcytic
* macrocytic
* Mean corpuscular hemoglobin concentration
* normochromic
* hypochromic

Other|

* Methemoglobinemia
* Sulfhemoglobinemia
* Reticulocytopenia
* Hereditary persistence of fetal hemoglobin

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