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Anisocytosis

MedGen UID:
66371
Concept ID:
C0221278
Finding
Synonyms: Anisocytosis, red cells; RBC's - anisocytosis; Unequal size of red blood cells
SNOMED CT: RBC's - anisocytosis (165475005); Anisocytosis, red cells (165475005); Anisocytosis (57241006)
 
HPO: HP:0011273

Definition

Abnormally increased variability in the size of erythrocytes. [from HPO]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVAnisocytosis

Conditions with this feature

Iron-refractory iron deficiency anemia
MedGen UID:
39081
Concept ID:
C0085576
Disease or Syndrome
Finberg et al. (2008) referred to this phenotype as iron-refractory iron deficiency anemia (IRIDA) and reviewed the key features: a congenital hypochromic, microcytic anemia; a very low mean corpuscular erythrocyte volume; a low transferrin saturation; abnormal iron absorption characterized by no hematologic improvement following treatment with oral iron; and abnormal iron utilization characterized by a sluggish, incomplete response to parenteral iron. The authors noted that although urinary levels of hepcidin (606464) are typically undetectable in individuals with iron deficiency, in 5 individuals with IRIDA urinary hepcidin/creatinine ratios were within or above the normal range.
Orotic aciduria
MedGen UID:
78642
Concept ID:
C0268128
Finding
Orotic aciduria is a rare autosomal recessive disorder characterized by megaloblastic anemia and orotic acid crystalluria that is frequently associated with some degree of physical and mental retardation. These features respond to appropriate pyrimidine replacement therapy, and most cases appear to have a good prognosis. A minority of cases have additional features, particularly congenital malformations and immune deficiencies, which may adversely affect this prognosis (summary by Webster et al., 2001). Bailey (2009) stated that only 2 cases of orotic aciduria without megaloblastic anemia (OAWA) had been reported.
X-linked sideroblastic anemia with ataxia
MedGen UID:
335078
Concept ID:
C1845028
Disease or Syndrome
X-linked sideroblastic anemia and ataxia is a rare condition characterized by a blood disorder called sideroblastic anemia and movement problems known as ataxia. This condition occurs only in males.\n\nSideroblastic anemia results when developing red blood cells called erythroblasts do not make enough hemoglobin, which is the protein that carries oxygen in the blood. People with X-linked sideroblastic anemia and ataxia have mature red blood cells that are smaller than normal (microcytic) and appear pale (hypochromic) because of the shortage of hemoglobin. This disorder also leads to an abnormal accumulation of iron in red blood cells. The iron-loaded erythroblasts, which are present in bone marrow, are called ring sideroblasts. These abnormal cells give the condition its name. Unlike other forms of sideroblastic anemia, X-linked sideroblastic anemia and ataxia does not cause a potentially dangerous buildup of iron in the body. The anemia is typically mild and usually does not cause any symptoms.\n\nX-linked sideroblastic anemia and ataxia causes problems with balance and coordination that appear early in life. The ataxia primarily affects the trunk, making it difficult to sit, stand, and walk unassisted. In addition to ataxia, people with this condition often have trouble coordinating movements that involve judging distance or scale (dysmetria) and find it difficult to make rapid, alternating movements (dysdiadochokinesis). Mild speech difficulties (dysarthria), tremor, and abnormal eye movements have also been reported in some affected individuals.
Anemia, nonspherocytic hemolytic, due to G6PD deficiency
MedGen UID:
403555
Concept ID:
C2720289
Disease or Syndrome
G6PD deficiency is the most common genetic cause of chronic and drug-, food-, or infection-induced hemolytic anemia. G6PD catalyzes the first reaction in the pentose phosphate pathway, which is the only NADPH-generation process in mature red cells; therefore, defense against oxidative damage is dependent on G6PD. Most G6PD-deficient patients are asymptomatic throughout their life, but G6PD deficiency can be life-threatening. The most common clinical manifestations of G6PD deficiency are neonatal jaundice and acute hemolytic anemia, which in most patients is triggered by an exogenous agent, e.g., primaquine or fava beans. Acute hemolysis is characterized by fatigue, back pain, anemia, and jaundice. Increased unconjugated bilirubin, lactate dehydrogenase, and reticulocytosis are markers of the disorder. The striking similarity between the areas where G6PD deficiency is common and Plasmodium falciparum malaria (see 611162) is endemic provided evidence that G6PD deficiency confers resistance against malaria (summary by Cappellini and Fiorelli, 2008).
Congenital dyserythropoietic anemia type 4
MedGen UID:
462276
Concept ID:
C3150926
Disease or Syndrome
Congenital dyserythropoietic anemia type IV (CDAN4) is an autosomal dominant red blood cell disorder characterized by ineffective erythropoiesis and hemolysis resulting in anemia. Circulating erythroblasts and erythroblasts in the bone marrow show various morphologic abnormalities. Affected individuals with CDAN4 also have increased levels of fetal hemoglobin (summary by Arnaud et al., 2010). For a discussion of genetic heterogeneity of congenital dyserythropoietic anemia, see CDAN1 (224120).
Mitochondrial complex V (ATP synthase) deficiency, nuclear type 1
MedGen UID:
477906
Concept ID:
C3276276
Disease or Syndrome
A distinct group of inborn defects of complex V (ATP synthase) is represented by the enzyme deficiency due to nuclear genome mutations characterized by a selective inhibition of ATP synthase biogenesis. Biochemically, the patients show a generalized decrease in the content of ATP synthase complex which is less than 30% of normal. Most cases present with neonatal-onset hypotonia, lactic acidosis, hyperammonemia, hypertrophic cardiomyopathy, and 3-methylglutaconic aciduria. Many patients die within a few months or years (summary by Mayr et al., 2010). Genetic Heterogeneity of Mitochondrial Complex V Deficiency Other nuclear types of mitochondrial complex V deficiency include MC5DN2 (614052), caused by mutation in the TMEM70 gene (612418) on chromosome 8q21; MC5DN3 (614053), caused by mutation in the ATP5E gene (ATP5F1E; 606153) on chromosome 20q13; MC5DN4A (620358) and MC5DN4B (615228), both caused by mutation in the ATP5A1 gene (ATP5F1A; 164360) on chromosome 18q; MC5DN5 (618120), caused by mutation in the ATP5D gene (ATP5F1D; 603150) on chromosome 19p13; MC5DN6 (618683), caused by mutation in the USMG5 gene (ATP5MD; 615204) on chromosome 10q24; and MC5DN7 (620359), caused by mutation in the ATP5PO gene (600828) on chromosome 21q22. Mutations in the mitochondrial-encoded MTATP6 (516060) and MTATP8 (516070) genes can also cause mitochondrial complex V deficiency (see, e.g., 500015).
X-linked dyserythropoetic anemia with abnormal platelets and neutropenia
MedGen UID:
763770
Concept ID:
C3550856
Disease or Syndrome
XLANP is an X-linked recessive hematologic disorder characterized by early-onset anemia and bone marrow erythroid hypoplasia with variable neutropenia. Some patients may have low platelets or platelet abnormalities. The severity is variable. Some patients have shown a favorable response to corticosteroid treatment (summary by Hollanda et al., 2006 and Sankaran et al., 2012). In some cases, the disorder may resemble Diamond-Blackfan anemia (see, e.g., DBA1; 105650) (Sankaran et al., 2012; Parrella et al., 2014; Klar et al., 2014).
Dyserythropoiesis, congenital, with ultrastructurally normal erythroblast heterochromatin
MedGen UID:
813565
Concept ID:
C3807235
Disease or Syndrome
The congenital dyserythropoietic anemias (CDAs) are an uncommon and heterogeneous group of conditions characterized by increased ineffective erythropoiesis and, usually, dysplastic changes in erythroblasts. Originally, 3 types of CDA were recognized and designated CDA type I (224120), type II (224100), and type III (105600). Subsequently, a number of other types were described, as reviewed by Wickramasinghe (1997). The defining features of CDA type I are autosomal recessive inheritance, macrocytes in the peripheral blood, internuclear chromatin bridges connecting some almost completely separated erythroblasts, and an abnormal ultrastructural appearance (spongy or 'swiss-cheese' appearance) of the heterochromatin in a high proportion of the erythroblasts.
Congenital dyserythropoietic anemia type type 1B
MedGen UID:
816515
Concept ID:
C3810185
Disease or Syndrome
Congenital dyserythropoietic anemia type I (CDA I) is characterized by moderate-to-severe macrocytic anemia presenting occasionally in utero as severe anemia associated with hydrops fetalis but more commonly in neonates as hepatomegaly, early jaundice, and intrauterine growth restriction. Some individuals present in childhood or adulthood. After the neonatal period, most affected individuals have lifelong moderate anemia, usually accompanied by jaundice and splenomegaly. Secondary hemochromatosis develops with age as a result of increased iron absorption even in those who are not transfused. Distal limb anomalies occur in 4%-14% of affected individuals.
Sideroblastic anemia 3
MedGen UID:
895975
Concept ID:
C4225155
Disease or Syndrome
Sideroblastic anemia-3 is an autosomal recessive hematologic disorder characterized by onset of anemia in adulthood. Affected individuals show signs of systemic iron overload, and iron chelation therapy may be of clinical benefit (summary by Liu et al., 2014). For a discussion of genetic heterogeneity of sideroblastic anemia, see SIDBA1 (300751).
Retinitis pigmentosa and erythrocytic microcytosis
MedGen UID:
934743
Concept ID:
C4310776
Disease or Syndrome
Features that occur less commonly in people with TRNT1 deficiency include hearing loss caused by abnormalities of the inner ear (sensorineural hearing loss), recurrent seizures (epilepsy), and problems with the kidneys or heart.\n\nTRNT1 deficiency encompasses what was first thought to be two separate disorders, a severe disorder called sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD) and a milder disorder called retinitis pigmentosa with erythrocytic microcytosis (RPEM), each named for its most common features. SIFD begins in infancy, and affected individuals usually do not survive past childhood. RPEM, on the other hand, is recognized in early adulthood, and the microcytosis usually does not cause any health problems. However, it has since been recognized that some individuals have a combination of features that fall between these two ends of the severity spectrum. All of these cases are now considered part of TRNT1 deficiency.\n\nNeurological problems are also frequent in TRNT1 deficiency. Many affected individuals have delayed development of speech and motor skills, such as sitting, standing, and walking, and some have low muscle tone (hypotonia).\n\nEye abnormalities, often involving the light-sensing tissue at the back of the eye (the retina), can occur in people with TRNT1 deficiency. Some of these individuals have a condition called retinitis pigmentosa, in which the light-sensing cells of the retina gradually deteriorate. Eye problems in TRNT1 deficiency can lead to vision loss.\n\nIn addition, many individuals with TRNT1 deficiency have recurrent fevers that are not caused by an infection. These fever episodes are often one of the earliest recognized symptoms of TRNT1 deficiency, usually beginning in infancy. The fever episodes are typically accompanied by poor feeding, vomiting, and diarrhea, and can lead to hospitalization. In many affected individuals, the episodes occur regularly, arising approximately every 2 to 4 weeks and lasting 5 to 7 days, although the frequency can decrease with age.\n\nMany people with TRNT1 deficiency have an immune system disorder (immunodeficiency) that can lead to recurrent bacterial infections. Repeated infections can cause life-threatening damage to internal organs. The immunodeficiency is characterized by low numbers of immune system cells called B cells, which normally help fight infections by producing immune proteins called antibodies (or immunoglobulins). These proteins target foreign invaders such as bacteria and viruses and mark them for destruction. In many individuals with TRNT1 deficiency, the amount of immunoglobulins is also low (hypogammaglobulinemia).\n\nA common feature of TRNT1 deficiency is a blood condition called sideroblastic anemia, which is characterized by a shortage of red blood cells (anemia). In TRNT1 deficiency, the red blood cells that are present are unusually small (erythrocytic microcytosis). In addition, developing red blood cells in the bone marrow (erythroblasts) can have an abnormal buildup of iron that appears as a ring of blue staining in the cell after treatment in the lab with certain dyes. These abnormal cells are called ring sideroblasts.\n\nTRNT1 deficiency is a condition that affects many body systems. Its signs and symptoms can involve blood cells, the immune system, the eyes, and the nervous system. The severity of the signs and symptoms vary widely.
RH-NULL, AMORPH TYPE
MedGen UID:
1639338
Concept ID:
C4693796
Disease or Syndrome
The RH-null phenotype designates rare individuals whose red blood cells lack all Rh antigens. Two RH-null types, the regulator type (RHNR; 268150) and the amorph type (RHNA), arising from independent genetic mechanisms have been distinguished. The regulator type is caused by mutation in the RHAG gene (180297). The amorph type arises from mutations at the RH locus itself that silence Rh expression. The RH locus contains the RHD (111680) and RHCE genes tandemly arranged at chromosome 1p36-p34. Four genes must therefore be silenced to produce the RH-null phenotype. The absence of the D antigen, produced by the RHD gene, is common in the human population; the D-negative phenotype may result from deletion or genetic alteration of the RHD gene. The RH-null amorph phenotype thus arises from inactivating mutations in RHCE on a D-negative background (summary by Huang et al., 1998 and Huang et al., 2000). Clinically, Rh-null patients present mild to moderate hemolytic anemia; cells exhibit characteristic morphologic and functional abnormalities including spherocytosis, stomatocytosis, and diminished lifespan. Rh-null patients rarely develop antibodies without stimulation, and most cases occur in response to pregnancy or transfusion (Silvy et al., 2015).
Fibrosis, neurodegeneration, and cerebral angiomatosis
MedGen UID:
1648312
Concept ID:
C4748939
Disease or Syndrome
Fibrosis, neurodegeneration, and cerebral angiomatosis (FINCA) is characterized by severe progressive cerebropulmonary symptoms, resulting in death in infancy from respiratory failure. Features include malabsorption, progressive growth failure, recurrent infections, chronic hemolytic anemia, and transient liver dysfunction. Neuropathology shows increased angiomatosis-like leptomeningeal, cortical, and superficial white matter vascularization and congestion, vacuolar degeneration and myelin loss in white matter, as well as neuronal degeneration. Interstitial fibrosis and granuloma-like lesions are seen in the lungs, and there is hepatomegaly with steatosis and collagen accumulation (Uusimaa et al., 2018).
Anemia, congenital dyserythropoietic, type 1a
MedGen UID:
1807106
Concept ID:
C5574667
Disease or Syndrome
Congenital dyserythropoietic anemia type I (CDA I) is characterized by moderate-to-severe macrocytic anemia presenting occasionally in utero as severe anemia associated with hydrops fetalis but more commonly in neonates as hepatomegaly, early jaundice, and intrauterine growth restriction. Some individuals present in childhood or adulthood. After the neonatal period, most affected individuals have lifelong moderate anemia, usually accompanied by jaundice and splenomegaly. Secondary hemochromatosis develops with age as a result of increased iron absorption even in those who are not transfused. Distal limb anomalies occur in 4%-14% of affected individuals.

Professional guidelines

PubMed

Horta-Baas G, Romero-Figueroa MDS
Int J Rheum Dis 2019 Jan;22(1):47-54. Epub 2018 Aug 30 doi: 10.1111/1756-185X.13332. PMID: 30168259
Danise P, Amendola G, Nobili B, Perrotta S, Miraglia Del Giudice E, Matarese SM, Iolascon A, Brugnara C
Clin Lab Haematol 2001 Feb;23(1):7-13. doi: 10.1046/j.1365-2257.2001.00354.x. PMID: 11422224
Miller WM
Clin Ther 1993 Jan-Feb;15(1):192-203; discussion 168. PMID: 8458049

Recent clinical studies

Etiology

Leung AKC, Lam JM, Wong AHC, Hon KL, Li X
Curr Pediatr Rev 2024;20(3):339-356. doi: 10.2174/1573396320666230727102042. PMID: 37497686
Jing J, Diao Y, Hao X, Zhao Y, Cheng X, Hu E, Lin J, Yuan C, Jia J, Liu J
Hematology 2023 Dec;28(1):2248433. doi: 10.1080/16078454.2023.2248433. PMID: 37642342
Bevan GH, Rana M, Al-Furaih N, Dalton J, Zidar DA, Al-Kindi SG
Heart Lung 2022 Jul-Aug;54:68-73. Epub 2022 Mar 28 doi: 10.1016/j.hrtlng.2022.03.013. PMID: 35358904
Salvagno GL, Sanchis-Gomar F, Picanza A, Lippi G
Crit Rev Clin Lab Sci 2015;52(2):86-105. Epub 2014 Dec 23 doi: 10.3109/10408363.2014.992064. PMID: 25535770
Vincent N, Barletta L, Laguens M
Aesthetic Plast Surg 2008 Sep;32(5):739-42. Epub 2008 Jun 13 doi: 10.1007/s00266-008-9181-3. PMID: 18551342

Diagnosis

Leung AKC, Lam JM, Wong AHC, Hon KL, Li X
Curr Pediatr Rev 2024;20(3):339-356. doi: 10.2174/1573396320666230727102042. PMID: 37497686
Jing J, Diao Y, Hao X, Zhao Y, Cheng X, Hu E, Lin J, Yuan C, Jia J, Liu J
Hematology 2023 Dec;28(1):2248433. doi: 10.1080/16078454.2023.2248433. PMID: 37642342
Salvagno GL, Sanchis-Gomar F, Picanza A, Lippi G
Crit Rev Clin Lab Sci 2015;52(2):86-105. Epub 2014 Dec 23 doi: 10.3109/10408363.2014.992064. PMID: 25535770
Latger-Cannard V, Fenneteau O, Salignac S, Lecompte TP, Schlegel N
Methods Mol Biol 2013;992:207-25. doi: 10.1007/978-1-62703-339-8_16. PMID: 23546716
Vincent N, Barletta L, Laguens M
Aesthetic Plast Surg 2008 Sep;32(5):739-42. Epub 2008 Jun 13 doi: 10.1007/s00266-008-9181-3. PMID: 18551342

Therapy

Leung AKC, Lam JM, Wong AHC, Hon KL, Li X
Curr Pediatr Rev 2024;20(3):339-356. doi: 10.2174/1573396320666230727102042. PMID: 37497686
Bevan GH, Rana M, Al-Furaih N, Dalton J, Zidar DA, Al-Kindi SG
Heart Lung 2022 Jul-Aug;54:68-73. Epub 2022 Mar 28 doi: 10.1016/j.hrtlng.2022.03.013. PMID: 35358904
Duchnowski P, Hryniewiecki T, Kuśmierczyk M, Szymański P
Cardiol J 2020;27(4):362-367. Epub 2019 Feb 25 doi: 10.5603/CJ.a2019.0020. PMID: 30799549Free PMC Article
Goyal H, Lippi G, Gjymishka A, John B, Chhabra R, May E
World J Gastroenterol 2017 Jul 21;23(27):4879-4891. doi: 10.3748/wjg.v23.i27.4879. PMID: 28785142Free PMC Article
Vincent N, Barletta L, Laguens M
Aesthetic Plast Surg 2008 Sep;32(5):739-42. Epub 2008 Jun 13 doi: 10.1007/s00266-008-9181-3. PMID: 18551342

Prognosis

Jing J, Diao Y, Hao X, Zhao Y, Cheng X, Hu E, Lin J, Yuan C, Jia J, Liu J
Hematology 2023 Dec;28(1):2248433. doi: 10.1080/16078454.2023.2248433. PMID: 37642342
Valenti AC, Vitolo M, Imberti JF, Malavasi VL, Boriani G
Curr Pharm Des 2021;27(37):3901-3912. doi: 10.2174/1381612827666210211125847. PMID: 33573547
Goyal H, Lippi G, Gjymishka A, John B, Chhabra R, May E
World J Gastroenterol 2017 Jul 21;23(27):4879-4891. doi: 10.3748/wjg.v23.i27.4879. PMID: 28785142Free PMC Article
Salvagno GL, Sanchis-Gomar F, Picanza A, Lippi G
Crit Rev Clin Lab Sci 2015;52(2):86-105. Epub 2014 Dec 23 doi: 10.3109/10408363.2014.992064. PMID: 25535770
Zvetkova E, Antonova N, Ivanov I, Savov Y, Gluhcheva Y
Clin Hemorheol Microcirc 2010;45(2-4):245-51. doi: 10.3233/CH-2010-1305. PMID: 20675906

Clinical prediction guides

Leung AKC, Lam JM, Wong AHC, Hon KL, Li X
Curr Pediatr Rev 2024;20(3):339-356. doi: 10.2174/1573396320666230727102042. PMID: 37497686
Jing J, Diao Y, Hao X, Zhao Y, Cheng X, Hu E, Lin J, Yuan C, Jia J, Liu J
Hematology 2023 Dec;28(1):2248433. doi: 10.1080/16078454.2023.2248433. PMID: 37642342
Goyal H, Lippi G, Gjymishka A, John B, Chhabra R, May E
World J Gastroenterol 2017 Jul 21;23(27):4879-4891. doi: 10.3748/wjg.v23.i27.4879. PMID: 28785142Free PMC Article
Salvagno GL, Sanchis-Gomar F, Picanza A, Lippi G
Crit Rev Clin Lab Sci 2015;52(2):86-105. Epub 2014 Dec 23 doi: 10.3109/10408363.2014.992064. PMID: 25535770
Vincent N, Barletta L, Laguens M
Aesthetic Plast Surg 2008 Sep;32(5):739-42. Epub 2008 Jun 13 doi: 10.1007/s00266-008-9181-3. PMID: 18551342

Recent systematic reviews

Lippi G, Henry BM, Mattiuzzi C
Scand J Clin Lab Invest 2024 Apr;84(2):79-83. Epub 2024 Mar 28 doi: 10.1080/00365513.2024.2332998. PMID: 38549291
Lippi G, Sanchis-Gomar F, Mattiuzzi C
Curr Probl Cardiol 2024 May;49(5):102476. Epub 2024 Feb 21 doi: 10.1016/j.cpcardiol.2024.102476. PMID: 38395117
Ligi D, Lo Sasso B, Henry BM, Ciaccio M, Lippi G, Plebani M, Mannello F
Clin Chem Lab Med 2023 May 25;61(6):960-973. Epub 2023 Jan 11 doi: 10.1515/cclm-2022-0936. PMID: 36626568
Sarkar S, Kannan S, Khanna P, Singh AK
Rev Med Virol 2022 Mar;32(2):e2264. Epub 2021 Jun 6 doi: 10.1002/rmv.2264. PMID: 34091982Free PMC Article
Paliogiannis P, Zinellu A, Mangoni AA, Capobianco G, Dessole S, Cherchi PL, Carru C
Biochem Med (Zagreb) 2018 Oct 15;28(3):030502. doi: 10.11613/BM.2018.030502. PMID: 30429667Free PMC Article

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