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Rh Deficiency Syndrome

Rh-null Syndrome

The Rh deficiency syndrome arises when all Rh factors are absent or are present in severely reduced amounts. There are two types of genetic defects that can lead to the deficiency; nevertheless, the phenotypic manifestations are the same because both lead to a decrease in the stability of the erythrocyte membrane. Thus, patients with the Rh deficiency syndrome display hemolytic anemia of varying severity.


Presentation

The Rh antigen system is a complex blood group system comprised of Rh proteins, Rh glycoproteins, and other associated proteins, all of which are components of the erythrocyte membrane. The complexity of these proteins has an important role in maintaining the integrity of the erythrocyte membrane. The RhD protein represents the Rh antigen D, and the RhCE protein is responsible for the C, c, E, and e antigenicity. Both proteins are encoded on chromosome 1 and have very similar amino acid sequences and structures, but are antigenically distinct [1]. The RhAG (Rh-associated glycoprotein) has limited (about 40%) similarity to the Rh proteins and is encoded on chromosome 6. The RhD and RhCE proteins form tetrameric complexes with RhAG; the complexes are thought to interact with accessory proteins, such as light-weight (LW) glycoprotein, integrin-associated protein (CD47), glycophorin B, and others [1]. Among these proteins the Rh antigen D is the most immunogenic: therefore, the presence or absence of the Rh D antigen - the Rh positive or negative status - is routinely determined in blood donors or recipients and pregnant women. Nevertheless, for various reasons, Rh immunization may still occur in pregnancy in mothers who lack the D antigen. The reaction may cause hemolytic disease of the newborn [1].

The Rh deficiency syndrome is defined by the absence of all Rh proteins (Rhnull), or by a very substantial reduction in their amounts (Rhmod). Other proteins that are absent or considerably reduced in this condition are RhAG and many of the accessory proteins (for example glycophorin B, LW and Fy5 glycoproteins, U and Duclos antigens) [2]. The Rh deficiency syndrome is either caused by a regulatory element that is located outside the Rh locus (regulatory type deficiency), or by the presence of silent Rh genes at the Rh locus (referred to as amorph type). The genetic defects, which may be due to various mutations or deletions or the combination of both, [3] are recessive in both cases. The symptoms of the disease, i.e. signs of chronic hemolytic anemia, are also the same and are associated with the anomalies in the erythrocyte cell’s membrane structure [4]. The condition is very rare: 1 in about six million is affected [1].

Patients with the Rh deficiency syndrome show signs of compensated hemolytic anemia, the severity of which is variable, with deformities in cell shape [5], i.e. stomatocytosis and spherocytosis. The osmotic fragility of erythrocytes is increased, and their lifespan is decreased. Cation transport and Na+/K+ adenosine triphosphatase activity are increased [6], leading to dehydration of the cell [4]. Another sign of disruption of membrane structure is an abnormal phospholipid distribution [7]. Patients may present with reticulocytosis [5].

Short Arm
  • ., 1974, Mapping human autosomes: Evidence supporting assignment of Rhesus to the short arm of chromosome no. 1, Science 184 : 966–968. CrossRef Google Scholar Merlie, J.[link.springer.com]

Workup

Patients with the Rh deficiency syndrome may be identified through routine testing, or because of signs of anemia. Family history may reveal consanguineous parentage [8].

Hematologic tests will show signs of mild hemolytic anemia, with somewhat low total hemoglobin, hematocrit, and mean corpuscular hemoglobin values [8]. The reticulocyte count may be higher than normal [5] [8]. The peripheral smear shows some cells with abnormal shapes i.e. stomatocytes and spherocytes. The osmotic fragility of red cells is examined by exposing them to various NaCl concentrations and following the degree of hemolysis: patients with the Rh deficiency syndrome have characteristically higher osmotic fragility than healthy individuals [5] [8]. The serum bilirubin concentration may be slightly increased because of the chronic hemolysis [5]. Monoclonal antibodies can be used to determine individual antigens within the Rh family of proteins and associated proteins. The tests will show that the Rh D, C, c, E, and e antigens, together with those for some other membrane glycoproteins are missing in cases with the Rh deficiency syndrome [8].

In patients with the Rhnull syndrome, antibodies to erythrocytes encountered through transfusion or during pregnancy may have specificities to one antigen (for example anti-C), a mixture of antigens, or all Rh antigens. These antibodies can be detected by the indirect antiglobulin test. The anti-total Rh antibody is called anti Rh29 [1] [2].

Treatment

  • […] the studies into 2 subgroups according to their focus on nonoperative treatments or operative treatments.[journals.lww.com]
  • In those cases that fail to respond in spite of aggressive systemic treatment, adjunctive intravitreal treatment should also be considered.[pmj.bmj.com]
  • For more information on fetal and newborn treatment, see Treatment Overview . If you are unsensitized Rh-negative, treatment focuses on preventing Rh sensitization during pregnancy and childbirth.[healthlinkbc.ca]
  • Minor’s consent for medical treatment related to rape – Family Code 6927: A minor who is 12 years of age or older and who is alleged to have been raped may consent to medical care related to the diagnosis or treatment of the condition and the collection[chhs.ca.gov]

Prognosis

  • View Rhnull syndrome Symptoms, Diagnosis, Treatments and … Rhnull syndrome information including symptoms, diagnosis, misdiagnosis, treatment, causes, patient stories, videos, forums, prevention, and prognosis.[nittru.com]
  • What should you tell the patient and the family about prognosis? G6PD deficiency is rarely a life-threatening illness and does not result in decreased survival.[cancertherapyadvisor.com]
  • Changing pattern of CMV retinitis In the past few years, a dramatic improvement in the prognosis for HIV-infected patients has been achieved with the strategy involving a combination of anti-retroviral drugs to bring about a profound and durable suppression[pmj.bmj.com]
  • PubMed Central PubMed Google Scholar Hochreutener H, Wüthrich B, Huwyler T, Schopfer K, Seger R, Baerlocher K: Variant of hyper-IgE syndrome: the differentiation from atopic dermatitis is important because of treatment and prognosis.[ojrd.biomedcentral.com]

Etiology

  • Etiology-Hereditary Familial Atypical Hemolytic-Uremic Syndrome (aHUS) (see Hemolytic-Uremic Syndrome , [[Hemolytic-Uremic Syndrome]]) xxx Hemoglobinopathies Sickle Cell Disease (see Sickle Cell Disease , [[Sickle Cell Disease]]) Unstable Hemoglobins[mdnxs.com]
  • A second hospitalization, beginning in June 1982, was complicated by Salmonella sepsis, perianal herpes simplex virus infection, encephalitis of unknown etiology, and disseminated cytomegalovirus infection. He died in August 1982.[cdc.gov]
  • Over the years, an intensive investigative effort has ensued in an attempt to find the etiology of IgG and IgG subclass deficiencies. However, these studies are controversial because of the heterogeneous nature of IgG deficiencies.[emedicine.medscape.com]
  • Causes of Vitamin B 12 Deficiency States Once vitamin B 12 deficiency is confirmed, a search for the etiology should be initiated.[aafp.org]
  • Her past history was significant for long-standing anaemia of mild to moderate severity of unknown etiology that did not respond to therapeutic trials with iron or other vitamin supplementations.[jpma.org.pk]

Epidemiology

  • […] ovalocytosis Synonym(s): - Rh-null syndrome Classification (Orphanet): - Rare genetic disease - Rare hematologic disease Classification (ICD10): - Diseases of the blood and blood-forming organs and certain disorders involving the immune mechanism - Epidemiological[csbg.cnb.csic.es]
  • Relevant External Links for RHAG Genetic Association Database (GAD) RHAG Human Genome Epidemiology (HuGE) Navigator RHAG Atlas of Genetics and Cytogenetics in Oncology and Haematology: RHAG No data available for Genatlas for RHAG Gene The monovalent cation[genecards.org]
  • Detection of insulin resistance by simple quantitative insulin sensitivity check index QUICKI for epidemiological assessment and prevention. J Clin Endocr Metab 2002;87: 144–7. Google Scholar 16. Wallace TM, Levy JC, Matthews DR.[degruyter.com]
  • Francis Memorial Hospital, S Dritz, MD, City/County Health Dept, San Francisco, J Chin, MD, State Epidemiologist, Calfornia State Dept. of Health Svcs; Field Svcs Div, Epidemiology Program Office, AIDS Activity, Div of Host Factors, Center for Infectious[cdc.gov]
  • Epidemiology The first cases of CMV retinitis in AIDS patients were reported in 1982. 3 4 It is now recognised as the most common retinal infection in patients with AIDS (table 1 ). 5 6 It tends to occur late in the course of the disease, and is associated[pmj.bmj.com]
Sex distribution
Age distribution

Pathophysiology

  • Pathophysiology G6PD is an enzyme that catalyzes the first step in the pentose phosphate shunt and provides RBCs with NADPH, need to curtail oxidative stress. The active form of G6PD is a dimer that contains tightly bound NADP.[cancertherapyadvisor.com]
  • Ongoing basic science and clinical research studies in hematology have improved our understanding of the pathophysiology of blood and coagulation diseases and improved our diagnostic tools.[my.clevelandclinic.org]

Prevention

  • If you are unsensitized Rh-negative, treatment focuses on preventing Rh sensitization during pregnancy and childbirth. Rh immune globulin (such as WinRho) is a highly effective treatment for preventing sensitization.[healthlinkbc.ca]
  • If you are unsensitized Rh-negative, treatment focuses on preventing Rh sensitization during pregnancy and childbirth. Rh immune globulin (such as RhoGAM) is a highly effective treatment for preventing sensitization.[mottchildren.org]
  • If the father of your child is Rh-positive or his blood type is unknown, receiving preventive treatment with immune globulins will prevent serious effects.[healthline.com]
  • Early diagnosis and treatment is critical to prevent neurologic injury, disability, poor outcomes, and premature death.[pharmacytimes.com]
  • Removal of the thymoma does not reverse the immunoglobulin deficiency, and patients may benefit from IgG replacement therapy to prevent recurrent infection.[emedicine.medscape.com]

References

Article

  1. Avent ND, Reid ME. The Rh blood group system: a review. Blood. 2000 Jan 15;95(2):375-387.
  2. Chérif-Zahar B, Raynal V, Le Van Kim C, et al. Structure and expression of the RH locus in the Rh-deficiency syndrome. Blood. 1993 Jul 15;82(2):656-562.
  3. Huang CH, Chen Y, Reid ME, Seidl C. Rhnull disease: the amorph type results from a novel double mutation in RhCe gene on D-negative background. Blood. 1998 Jul 15;92(2):664-671.
  4. Cartron JP. Rh-deficiency syndrome. Lancet. 2001 Dec;358 Suppl:S57.
  5. Sturgeon P. Hematological observations on the anemia associated with blood type Rhnull. Blood. 1970 Sep;36(3):310-320.
  6. Lauf PK, Joiner CH. Increased potassium transport and ouabain binding in human Rhnull red blood cells. Blood. 1976 Sep;48(3):457-468.
  7. Kuypers F, van Linde-Sibenius-Trip M, Roelofsen B, Tanner MJ, Anstee DJ, Op den Kamp JA. Rhnull human erythrocytes have an abnormal membrane phospholipid organization. Biochem J. 1984 Aug 1;221(3):931-934.
  8. Qureshi A, Salman M, Moiz B. Rhnull: a rare blood group phenotype. J Pak Med Assoc. 2010 Nov;60(11):960-961.

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Last updated: 2018-06-22 00:35