Hereditary Red Cell Membrane Disorders Research Articles

NEONATAL HAEMOLYTIC ANAEMIA- A DIAGNOSTIC APPROACH TO RED CELL MEMBRANE DISORDERS

In neonates presenting with a non-immune haemolytic anaemia, a high index of suspicion is raised for hereditary red cell membrane disorders. The distinction between red cell membrane disorders, however, is often difficult in neonates in the absence of a complete family history. We describe a case of a 26-day-old female twin who presented with jaundice and severe haemolysis, which required multiple red cell transfusions. Laboratory investigations revealed a non-immune haemolysis. Red cell membrane extraction and sodium dodecyl sulphate-polyacrylamide gel electrophoresis analysis, including spectrin analysis, revealed the presence of mutant spectrin αI/74. A diagnosis of hereditary elliptocytosis with transient infantile poikilocytosis was favoured. On follow-up at 4 months, a decline in haemolysis was observed.

ICSH guidelines for the laboratory diagnosis of nonimmune hereditary red cell membrane disorders.

Hereditary spherocytosis (HS), hereditary elliptocytosis (HE), and hereditary stomatocytosis (HSt) are inherited red cell disorders caused by defects in various membrane proteins. The heterogeneous clinical presentation, biochemical and genetic abnormalities in HS and HE have been well documented. The need to raise the awareness of HSt, albeit its much lower prevalence than HS, is due to the undesirable outcome of splenectomy in these patients. The scope of this guideline is to identify the characteristic clinical features, the red cell parameters (including red cell morphology) for these red cell disorders associated, respectively, with defective cytoskeleton (HS and HE) and abnormal cation permeability in the lipid bilayer (HSt) of the red cell. The current screening tests for HS are described, and their limitations are highlighted. An appropriate diagnosis can often be made when the screening test result(s) is reviewed together with the patient's clinical/family history, blood count results, reticulocyte count, red cell morphology, and chemistry results. SDS-polyacrylamide gel electrophoresis of erythrocyte membrane proteins, monovalent cation flux measurement, and molecular analysis of membrane protein genes are specialist tests for further investigation. Specialist tests provide additional evidence in supporting the diagnosis and that will facilitate the management of the patient. In the case of a patient's clinical phenotype being more severe than the affected members within the immediate family, molecular testing of all family members is useful for confirming the diagnosis and allows an insight into the molecular basis of the abnormality such as a recessive mode of inheritance or a de novo mutation.

Ektacytometry and genetic testing in hereditary red cell membrane disorders

International Journal of Laboratory HematologyVolume 36, Issue 1 p. 107-107 Letter to the Editor Ektacytometry and genetic testing in hereditary red cell membrane disorders A. Huisman, A. Huisman [email protected] Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, The NetherlandsSearch for more papers by this authorR. van Wijk, R. van Wijk Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, The NetherlandsSearch for more papers by this author A. Huisman, A. Huisman [email protected] Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, The NetherlandsSearch for more papers by this authorR. van Wijk, R. van Wijk Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, The NetherlandsSearch for more papers by this author First published: 06 September 2013 https://doi.org/10.1111/ijlh.12140Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume36, Issue1February 2014Pages 107-107 RelatedInformation

Response to a letter from A. Huisman and R. van Wijk (Ektacytometry and Genetic Testing in Hereditary Red Cell Membrane Disorders)

Response to a letter from A. Huisman and R. van Wijk (Ektacytometry and Genetic Testing in Hereditary Red Cell Membrane Disorders)

Hereditary red cell membrane disorders and laboratory diagnostic testing

This overview describes two groups of nonimmune hereditary hemolytic anemias caused by defects in membrane proteins located in distinct layers of the red cell membrane. Hereditary spherocytosis (HS), hereditary elliptocytosis (HE), and hereditary pyropoikilocytosis (HPP) represent disorders of the red cell cytoskeleton. Hereditary stomatocytoses represents disorders of cation permeability in the red cell membrane. The current laboratory screening tests for HS are the osmotic fragility test, acid glycerol lysis time test (AGLT), cryohemolysis test, and eosin-5'-maleimide (EMA)-binding test. For atypical HS, SDS-polyacrylamide gel electrophoresis of erythrocyte membrane proteins is carried out to confirm the diagnosis. The diagnosis of HE/HPP is based on abnormal red cell morphology and the detection of protein 4.1R deficiency or spectrin variants using gel electrophoresis. None of screening tests can detect all HS cases. Some testing centers (a survey of 25 laboratories) use a combination of tests (e.g., AGLT and EMA). No specific screening test for hereditary stomatocytoses is available. The preliminary diagnosis is based on presenting a compensated hemolytic anemia, macrocytosis, and a temperature or time dependent pseudohyperkalemia in some patients. Both the EMA-binding test and the osmotic fragility test may help in differential diagnosis of HS and hereditary stomatocytosis.

The molecular basis of hereditary red cell membrane disorders

The red cell membrane is one of the best known membranes in terms of structure, function and genetic disorders. As any plasma membrane it mediates transport functions. It also provides the erythrocytes with their resilience and deformability. Many of the proteins and the genes performing these functions are known in great detail, although some disease-responsible genes are yet to be elucidated. Basic knowledge has shed light on important groups of genetic disorders. The latter include (i) the disorders of the red cell mechanics: hereditary spherocytosis, hereditary elliptocytosis and poikilocytosis, and (ii) the disorders of the passive flux of the monovalent cations across the membrane: the stomacytoses and allied conditions. Reciprocally, many information have come from genetics abnormalities. We will review the mutation-disease relationship. A number of points will be underscored: widespread weak alleles modulate the expression of the SPTA1 gene, encoding the alpha-chain of spectrin; mutations in the anion exchanger can give rise to an array of distinct nosological entities, including a renal condition; splenectomy is banned in the stomatocytoses; a variety of stomatocyosis is part of a pleiotropic syndrome that may includes perinatal fetal liquid effusions. The diagnosis, follow-up and treatment of the involved diseases have gradually improved.

Genotyping and phenotyping characteristics in hereditary red cell membrane disorders

Genotyping and phenotyping characteristics in hereditary red cell membrane disorders