Acquired elliptocytosis in chronic myeloid neoplasms: An enigmatic relationship to acquired red cell membrane protein and genetic abnormalities.

Nineteen reports of 41 cases of acquired red cell elliptocytosis associated with a chronic myeloid neoplasm are described. Although the majority of cases have an abnormality of the long arm of chromosome 20, del(q20), several cases do not. Moreover, in one case a specific qualitative abnormality of red cell protein band 4.1(4.1R) was reported; however, several subsequent cases could find no abnormality of a red cell membrane protein or found a different abnormality, usually quantitative. Thus, this striking red cell phenotypic feature, acquired elliptocytosis, seen in myelodysplastic syndrome and other chronic myeloproliferative diseases, closely simulating the red cell phenotype of hereditary elliptocytosis, has an unexplained genetic basis, presumably as the result of an acquired mutation(s) in some chronic myeloid neoplasms.

A Novel α-Spectrin Pathogenic Variant in Trans to α-Spectrin LELY Causing Neonatal Jaundice With Hemolytic Anemia From Hereditary Pyropoikilocytosis Coexisting With Gilbert Syndrome.

Hereditary pyropoikilocytosis is a subtype of hereditary elliptocytosis because of biallelic mutations of SPTA1, SPTB, and EPB41. The authors present a proband with neonatal jaundice and hemolytic anemia, with poikilocytosis in the blood film. Targeted next-generation sequencing identified Q267del trans to the αLELY allele in SPTA1. In addition, the proband presented coexisting Gilbert syndrome as determined by homozygous mutation of UGT1A1. Investigation of 13 relatives and his sibling revealed that only his sibling showed the same phenotype and genotype as the proband. This is the first report of molecular confirmation of coexisting hereditary pyropoikilocytosis and Gilbert syndrome and a novel mutation in SPTA1.

A case series of distal renal tubular acidosis, Southeast Asian ovalocytosis and metabolic bone disease.

BACKGROUND: Familial distal renal tubular acidosis (dRTA) associated with mutations of solute carrier family 4 membrane - 1 (SLC4A1) gene could co-exist with red cell membrane abnormality, Southeast Asian ovalocytosis (SAO). Although this association is well described in Southeast Asian countries, it is less frequently found in Sri Lanka. CASE PRESENTATION: We describe six patients who had dRTA co-existing with SAO. All of them initially presented with severe hypokalemia and paralysis. They presented within a period of six months to the Teaching Hospital Anuradhapura, Sri Lanka. All had metabolic acidosis indicated by low serum bicarbonate. Three of them were having underlying chronic kidney disease as well. Those three patients had mixed high and normal anion gap metabolic acidosis indicated by low delta ratio. In all dRTA was confirmed by presence of normal anion gap, hyperchloraemia, high urine pH and positive urine anion gap. Examination of blood films of all of them revealed presence of stomatocytes and macro-ovalocytosis compatible with SAO. In relation to complications of dRTA, two patients had medullary nephrocalcinosis. Three patients had biochemical evidence of osteomalacia, with two of them having radiological evidence of diffuse osteosclerosis. One patient had secondary hyperparathyroidism and a pathological fracture. CONCLUSIONS: Erythrocyte in SAO is exceptionally rigid and this abnormality is said to be evolved as it protects against Plasmodium vivax malaria and cerebral malaria cause by Plasmodium falciparum. Although two families of SAO was described earlier, SAO and dRTA combination was reported only once in a patient from Anuradhapura district. Distal renal tubular acidosis, SAO combination and its related complications including nephrocalcinosis, chronic kidney disease and metabolic bone disease was not described in Sri-Lankan literature. This case series emphasize the importance of investigating recurrent/ chronic hypokalemia to diagnose dRTA and its associations, as early correction of acidosis could prevent development of chronic kidney disease and metabolic bone disease.

Coinheritance of Hereditary Elliptocytosis and Deletional Hemoglobin H Disease.

Hereditary elliptocytosis is an inherited red blood cell membrane disorder characterized by typical peripheral blood smear findings of elliptocytes or rod-like red blood cells. Hemoglobin H disease is a form of α-thalassemia disease resulting in mild to moderate hemolytic anemia. The authors report 1 case of a girl who was diagnosed with oculo-auriculo-vertebral spectrum and a coinheritance of hereditary elliptocytosis and deletional hemoglobin H disease. She had moderate, non-transfusion-dependent anemia. The red blood cells showed marked poikilocytosis and fragmentation. The parents were α-thalassemia carriers and the father had the typical red blood cell morphology of common hereditary elliptocytosis.

An usual cause of elliptocytosis.

We report a 60-year-old adult case with a normocytic normochromic regenerative anemia discovered incidentally. The objectification of elliptocytosis accompanied by splenomegaly, a collagen myelofibrosis and the presence of the mutation JAK2V617F allowed the diagnosis of primary myelofibrosis with atypical initial presentation. The causes of elliptocytoses are discussed.

Atypical hereditary ovalocytosis associated with defective dyserythropoietic anemia.

The cases of a child and his mother affected by chronic anemia with atypical elliptocytosis are reported. When adolescent the mother underwent splenectomy, with an incomplete response. Anemia was characterized by a morphological picture of ovalocytosis associated with a significant percentage of spherocytes in the peripheral blood of the child and spiculated red cells in that of the splenectomized mother. Bone marrow aspirates of the child showed a striking erythropoietic hyperplasia with marked decrease of mature cells and dyserythropoietic features. Reticulocyte count was rather low. Ferrokinetics showed ineffective erythropoiesis. Biochemical studies on red blood cell membrane cytoskeleton showed that beta-spectrin, alpha-spectrin and protein 4.1, which are usually altered in hereditary elliptocytosis (HE), were normal in our cases. This report confirms the hypothesis of Torlontano who postulated the existence of a distinct atypical form of HE associated with ineffective and dysplastic erythropoiesis.

Invasion of hereditary ovalocytes by Plasmodium falciparum in vitro and its relation to intracellular ATP concentration.

Hereditary ovalocytes (stomatocytic ovalocytes), when examined within 1-2 days from the time that the blood sample is drawn, are invaded by Plasmodium falciparum in culture to the extent of at least 55% of normal control cells. The ovalocytes have extremely rigid membranes, characterised by a shear elastic modulus some 3-4 times greater than that of normal cells. The extent of invasion falls off very much more rapidly than that into normal cells on storage, and we surmise that this is the reason for earlier reports of resistance of ovalocytes to malarial invasion in vitro. The initial loss of susceptibility to invasion with time is not accompanied by any change in membrane rigidity, but is primarily a consequence of a rapid decline in intracellular ATP concentration: this falls to below the threshold level required for invasion (approx. 0.1 mM) over a period in which the ATP in normal cells remains almost constant. Incubation in a metabolic regenerating medium leads to a rise in the intracellular ATP concentration and invasion by P. falciparum is recovered, though to a much lower extent than in normal cells. The resistance of ovalocytes to invasion becomes irreversible, due possibly to degradative processes in the membrane, on further storage. The developing parasites in ovalocytes have a reduced number of merozoites and show distinct morphological abnormalities.

Eliptocitosis hereditaria con anemia hemolítica durante el embarazo / Hereditary eliptocitosis with hemolytic anemia during pregnancy

Se presenta un caso inusual de eliptocitosis hereditaria con anemia hemolítica para ilustrar como este defecto hereditario de los eritrocitos puede complicar el embarazo

Eliptocitosis hereditaria con anemia hemolítica durante el embarazo: reporte de un caso y revisión de la literatura

Un caso inusual de eliptocitosis hereditaria con anemia hemolítica es presentado, para ilustrar cómo este defecto hereditario de los eritrocitos puede complicar el embarazo

Elliptocytosis preceding myelofibrosis in a patient with polycythemia vera.

A patient with polycythemia vera showed marked elliptocytosis in the peripheral blood, 2 years after the diagnosis was established. 4 years later on, the patient developed myelofibrosis. The significance of elliptocytosis, which appears during the course of polycythemia vera, as an early indicator for the development of myelofibrosis is discussed.

The pyropoikilocytosis-elliptocytosis syndrome in a black South African infant: clinical and hematological features.

A black infant presented in the newborn period with severe red cell fragmentation, pyknocytosis, and hemolysis necessitating repeated exchange transfusions. Exposure of the red cells to 45 degrees C in vitro caused membrane budding, fragmentation, and sphering similar to that described in pyropoikilocytosis. By 12 months of age the clinical and hematologic picture had evolved to one of a compensated hemolytic disorder with elliptocytosis, but the degree of abnormal thermal sensitivity remained unchanged. Osmotic fragility and authohemolysis tests gave results intermediate between hereditary elliptocytosis and hereditary pyropoikilocytosis. It appears that there is considerable heterogeneity within the red cell membrane disorders exhibiting altered thermal sensitivity.

Hereditary haemolytic ovalocytosis with defective erythropoiesis.

Patients belonging to four families with 'atypical elliptocytosis' have been investigated. Clinical, haematological, erythrokinetic and enzymatic characteristics as well as the effect of splenectomy are discussed. These studies appear to define the fundamental features of a particular disorder or a variety of hereditary elliptocytosis; characterized by a genetic autosomal dominant character, moderate degree of RBC eccentricity, erythroid dysplasia with relative marrow failure and incomplete response to splenectomy.

The use of nuclear medicine procedures in the diagnosis of Budd-Chiari syndrome.

The case history of a patient with Budd-Chiari syndrome (BCS) is described. The underlaying disease proved to be essential thrombocytosis. Congential elliptocytosis was also present. The value of the conventional liver scan, percutaneous splenoportoscintigraphy and isotopic phlebography of the inferior vena cava in the diagnosis of BCS is described. It is suggested that a combination of these three noninvasive techniques be used when BCS is suspected.

Haemoglobin Lepore Boston and elliptocytosis in a family of Indonesian-German ancestry.

A family is presented in which Hb Lepore Boston was found in six individuals over three generations. The gene must have had its origin either in Java (Indonesia) or in what is now the Federal Republic of Germany. The haemoglobin was characterized by amino-acid analysis of the six tryptic peptides that have a different composition in the beta- and the delta-chain. The ratio of glycine to alanine in position 136 of the fetal haemoglobin, which was somewhat raised in the Hb Lepore carriers, averaged 31:39. In addition an elliptocytosis gene was found, which was inherited independently from Hb Lepore; the simultaneous presence of elliptocytosis in three family members did not seem to aggravate the mild anaemia caused by Hb Lepore.