Hemoglobin Lepore syndrome

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Hemoglobin Lepore syndrome
Other namesHb Lepore syndrome
Hemoglobin.jpg
A crossover between the delta and beta globin gene loci results in the mutation which causes the Hb Lepore trait.

Hemoglobin Lepore syndrome is typically an asymptomatic hemoglobinopathy, which is caused by an autosomal recessive genetic mutation. The Hb Lepore variant, consisting of two normal alpha globin chains (HBA) and two delta-beta globin fusion chains which occurs due to a "crossover" between the delta (HBD) and beta globin (HBB) gene loci during meiosis and was first identified in the Lepore family, an Italian-American family, in 1958. [1] There are three varieties of Hb Lepore, Washington (Hb Lepore Washington, AKA Hb Lepore Boston or Hb Lepore Washington-Boston), Baltimore (Hb Lepore Baltimore) and Hollandia (Hb Hollandia). All three varieties show similar electrophoretic and chromatographic properties and hematological findings bear close resemblance to those of the beta-thalassemia trait; a blood disorder that reduces the production of the iron-containing protein hemoglobin which carries oxygen to cells and which may cause anemia.

Contents

The homozygous state for Hb Lepore is rare. Patients of Balkan descent tend to have the most severe presentation of symptoms including severe anemia during the first five years of life. They also presented with significant splenomegaly, hepatomegaly, and skeletal abnormalities identical to those of homozygous beta-thalassemia. The amount of Hb Lepore in the patients blood ranged from 8 to 30%, the remainder being fetal hemoglobin (Hb F) which is present in minute quantities (typically<1 percent) in the red blood cells of adults. Known as F- cells they are present in a small proportion of overall RBCs. [2]

Homozygous Hb Lepore is similar to beta-thalassemia major; however, the clinical course is variable. Patients with this condition typically present with severe anemia during the first two years of life. The heterozygote form is mildly anemic (Hb 11–13 g/dl) but presents with a significant hypochromia (deficiency of hemoglobin in the red blood cells) and microcytosis. [3] [4]

Presentation

Complications

A potential complication that may occur in children that suffer acute anemia with a hemoglobin count below 5.5 g/dl is silent stroke [5] [ unreliable medical source? ] A silent stroke is a type of stroke that does not have any outward symptoms (asymptomatic), and the patient is typically unaware they have suffered a stroke. Despite not causing identifiable symptoms a silent stroke still causes damage to the brain, and places the patient at increased risk for both transient ischemic attack and major stroke in the future. [6]

Cause

Sickle cell-Hb Lepore Boston syndrome is a type of sickle cell disease (HbS) that differs from homozygous sickle cell disease where both parents carry sickle hemoglobin. In this variant one parent has the sickle cell hemoglobin the second parent has Hb Lepore Boston, the only one of the three variants described in association with HbS. [7]

Diagnosis

The diagnosis of Hb Lepore syndrome may be performed antenatally or postnatally via the use of a variety of tests

Treatment

Homozygous Hb Lepore

Those homozygous (Hb LeporeLepore; a very rare situation) or compound heterozygous (Hb Lepore-Β-thalassaemia) might suffer from a severe anaemia. They should be managed in a comprehensive multi-disciplinary program of care. [10] Management includes a regular course of blood transfusions, although the clinical severity in compound (double) heterozygotes can range from minor to major, depending on the combination of genes that have caused the condition. [11]

Heterozygous Hb Lepore

Individuals heterozygous for the Hb Lepore require no particular treatment. There is no anemia or, if there is, it is very mild. [10]

Epidemiology

The Hb Lepore trait has a worldwide distribution and may affect individuals of various ethnicities however the three main varieties which been defined tend to be more prevalent among specific ethnic groups, typically Caucasians of the Southern regions Central and Eastern Europe. The three main varieties are named for the geographical areas they were first identified in with various subtypes, the three main varieties are:[ citation needed ]

Related Research Articles

<span class="mw-page-title-main">Hemoglobinopathy</span> Any of various genetic disorders of blood

Hemoglobinopathy is the medical term for a group of inherited blood disorders involving the hemoglobin, the protein of red blood cells. They are single-gene disorders and, in most cases, they are inherited as autosomal co-dominant traits.

<span class="mw-page-title-main">Thalassemia</span> Family of inherited blood disorders

Thalassemias are inherited blood disorders that result in abnormal hemoglobin. Symptoms depend on the type of thalassemia and can vary from none to severe. Often there is mild to severe anemia 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. Symptoms and presentations of thalassemia can change over time. Thalassemia is also known as Cooley's anemia or Mediterranean anemia.

<span class="mw-page-title-main">Fetal hemoglobin</span> Oxygen carrier protein in the human fetus

Fetal hemoglobin, or foetal haemoglobin is the main oxygen carrier protein in the human fetus. Hemoglobin F is found in fetal red blood cells, and is involved in transporting oxygen from the mother's bloodstream to organs and tissues in the fetus. It is produced at around 6 weeks of pregnancy and the levels remain high after birth until the baby is roughly 2–4 months old. Hemoglobin F has a different composition than adult forms of hemoglobin, allowing it to bind oxygen more strongly; this in turn enables the developing fetus to retrieve oxygen from the mother's bloodstream, which occurs through the placenta found in the mother's uterus.

<span class="mw-page-title-main">Hemoglobin A</span> Normal human hemoglobin in adults

Hemoglobin A (HbA), also known as adult hemoglobin, hemoglobin A1 or α2β2, is the most common human hemoglobin tetramer, accounting for over 97% of the total red blood cell hemoglobin. Hemoglobin is an oxygen-binding protein, found in erythrocytes, which transports oxygen from the lungs to the tissues. Hemoglobin A is the most common adult form of hemoglobin and exists as a tetramer containing two alpha subunits and two beta subunits (α2β2). Hemoglobin A2 (HbA2) is a less common adult form of hemoglobin and is composed of two alpha and two delta-globin subunits. This hemoglobin makes up 1-3% of hemoglobin in adults.

Hemoglobin A2 (HbA2) is a normal variant of hemoglobin A that consists of two alpha and two delta chains (α2δ2) and is found at low levels in normal human blood. Hemoglobin A2 may be increased in beta thalassemia or in people who are heterozygous for the beta thalassemia gene.

Hemoglobin C is an abnormal hemoglobin in which glutamic acid residue at the 6th position of the β-globin chain is replaced with a lysine residue due to a point mutation in the HBB gene. People with one copy of the gene for hemoglobin C do not experience symptoms, but can pass the abnormal gene on to their children. Those with two copies of the gene are said to have hemoglobin C disease and can experience mild anemia. It is possible for a person to have both the gene for hemoglobin S and the gene for hemoglobin C; this state is called hemoglobin SC disease, and is generally more severe than hemoglobin C disease, but milder than sickle cell anemia.

<span class="mw-page-title-main">Alpha-thalassemia</span> Thalassemia involving the genes HBA1and HBA2 hemoglobin genes

Alpha-thalassemia is a form of thalassemia involving the genes HBA1 and HBA2. Thalassemias are a group of inherited blood conditions which result in the impaired production of hemoglobin, the molecule that carries oxygen in the blood. Normal hemoglobin consists of two alpha chains and two beta chains; in alpha-thalassemia, there is a quantitative decrease in the amount of alpha chains, resulting in fewer normal hemoglobin molecules. Furthermore, alpha-thalassemia leads to the production of unstable beta globin molecules which cause increased red blood cell destruction. The degree of impairment is based on which clinical phenotype is present.

<span class="mw-page-title-main">Sickle cell trait</span> Medical condition

Sickle cell trait describes a condition in which a person has one abnormal allele of the hemoglobin beta gene, but does not display the severe symptoms of sickle cell disease that occur in a person who has two copies of that allele. Those who are heterozygous for the sickle cell allele produce both normal and abnormal hemoglobin.

<span class="mw-page-title-main">Beta thalassemia</span> Blood disorder

Beta thalassemias are a group of inherited blood disorders. They are forms of thalassemia caused by reduced or absent synthesis of the beta chains of hemoglobin that result in variable outcomes ranging from severe anemia to clinically asymptomatic individuals. Global annual incidence is estimated at one in 100,000. Beta thalassemias occur due to malfunctions in the hemoglobin subunit beta or HBB. The severity of the disease depends on the nature of the mutation.

<span class="mw-page-title-main">Hemoglobin subunit beta</span> Mammalian protein found in Homo sapiens

Hemoglobin subunit beta is a globin protein, coded for by the HBB gene, which along with alpha globin (HBA), makes up the most common form of haemoglobin in adult humans, hemoglobin A (HbA). It is 147 amino acids long and has a molecular weight of 15,867 Da. Normal adult human HbA is a heterotetramer consisting of two alpha chains and two beta chains.

<span class="mw-page-title-main">Hemoglobin variants</span> Forms of hemoglobin caused by variations in genetics

Hemoglobin variants are different types of hemoglobin molecules, by different combinations of its subunits and/or mutations thereof. Hemoglobin variants are a part of the normal embryonic and fetal development. They may also be pathologic mutant forms of hemoglobin in a population, caused by variations in genetics. Some well-known hemoglobin variants, such as sickle-cell anemia, are responsible for diseases and are considered hemoglobinopathies. Other variants cause no detectable pathology, and are thus considered non-pathological variants.

Hemoglobin Barts, abbreviated Hb Barts, is an abnormal type of hemoglobin that consists of four gamma globins. It is moderately insoluble, and therefore accumulates in the red blood cells. Hb Barts has an extremely high affinity for oxygen, so it cannot release oxygen to the tissue. Therefore, this makes it an inefficient oxygen carrier. As an embryo develops, it begins to produce alpha-globins at weeks 5–6 of development. When both of the HBA1 and HBA2 genes which code for alpha globins becomes dysfunctional, the affected fetuses will have difficulty in synthesizing a functional hemoglobin. As a result, gamma chains will accumulate and form four gamma globins. These gamma globins bind to form hemoglobin Barts. It is produced in the disease alpha-thalassemia and in the most severe of cases, it is the only form of hemoglobin in circulation. In this situation, a fetus will develop hydrops fetalis and normally die before or shortly after birth, unless intrauterine blood transfusion is performed.

<span class="mw-page-title-main">Hemoglobin subunit alpha</span> Human hemoglobin protein

Hemoglobin subunit alpha, Hemoglobin, alpha 1, is a hemoglobin protein that in humans is encoded by the HBA1 gene.

<span class="mw-page-title-main">Hemoglobin E</span> Medical condition

Hemoglobin E (HbE) is an abnormal hemoglobin with a single point mutation in the β chain. At position 26 there is a change in the amino acid, from glutamic acid to lysine (E26K). Hemoglobin E is very common among people of Southeast Asian, Northeast Indian, Sri Lankan and Bangladeshi descent.

<span class="mw-page-title-main">Delta-beta thalassemia</span> Medical condition

Delta-beta thalassemia is a rare form of thalassemia in which there is a reduced production of hemoglobin subunit delta and hemoglobin subunit beta and raised levels of hemoglobin subunit gamma. It is an autosomal recessive disorder.

Within the medical specialty of hematology, Hemoglobin D-Punjab, also known as hemoglobin D-Los Angeles, D-North Carolina, D-Portugal, D-Oak Ridge, and D-Chicago, is a hemoglobin variant. It originates from a point mutation in the human β-globin locus and is one of the most common hemoglobin variants worldwide. It is so named because of its higher prevalence in the Punjab region of India and Pakistan, along with northern China, and North America. It is also the most frequent hemoglobin variant in Xinjiang Uyghur Autonomous Region of China, with a 1997 study indicating that Hemoglobin D-Punjab accounts for 55.6% of the total hemoglobin variants.

Sickle cell-beta thalassemia is an inherited blood disorder. The disease may range in severity from being relatively benign and like sickle cell trait to being similar to sickle cell disease.

Hemoglobin H disease, also called alpha-thalassemia intermedia, is a disease affecting hemoglobin, the oxygen carrying molecule within red blood cells. It is a form of Alpha-thalassemia which most commonly occurs due to deletion of 3 out of 4 of the α-globin genes.

Hemoglobin O (HbO) is a rare type of hemoglobin in which there is a substitution of glutamic acid by lysine as in hemoglobin C, but at different positions. Since the amino acid substitution can occur at different positions of the β-globin chain of the protein, there are several variants. In hemoglobin O-Arab (HbO-Arab) substitution occurs at position 121, while in hemoglobin O-Padova (HbO-Padova) it is at 11 position, and in hemoglobin O Indonesia (HbOIna) it is at 116.

Hemoglobin D (HbD) is a variant of hemoglobin, a protein complex that makes up red blood cells. Based on the locations of the original identification, it has been known by several names such as hemoglobin D-Los Angeles, hemoglobin D-Punjab, D-North Carolina, D-Portugal, D-Oak Ridge, and D-Chicago. Hemoglobin D-Los Angeles was the first type identified by Harvey Itano in 1951, and was subsequently discovered that hemoglobin D-Punjab is the most abundant type that is common in the Sikhs of Punjab and of Gujarat.

References

  1. ↑ Gerald PS, Diamond LK (September 1958). "A new hereditary hemoglobinopathy (the Lepore trait) and its interaction with thalassemia trait". Blood. 13 (9): 835–44. doi: 10.1182/blood.v13.9.835.835 . PMID   13572441.
  2. ↑ Rochette J, Craig JE, Thein SL (December 1994). "Fetal hemoglobin levels in adults". Blood Rev. 8 (4): 213–24. doi:10.1016/0268-960x(94)90109-0. PMID   7534152.
  3. ↑ Ricci G, Scutellari PN, Franceschini F, Gualandi G (February 1982). "[A new case of hemoglobin Lepore-beta-thalassemia disease]". Minerva Med. (in Italian). 73 (5): 191–7. PMID   7063135.
  4. ↑ Efremov GD, Rudivić R, Niazi GA, et al. (February 1976). "An individual with Hb-Lepore-Baltimore- delta beta-thalassaemia in a Yugoslavian family". Scand J Haematol. 16 (2): 81–9. doi:10.1111/j.1600-0609.1976.tb01122.x. PMID   1257702.
  5. ↑ Dowling MM, Quinn CT, Plumb P, Rogers ZR, Rollins N, Koral K, Barber R, Buchanan GR (11 February 2011). "Acute anemia linked to silent strokes in children American Stroke Association Meeting Report: Abstract 185". American Heart Association. Archived from the original on 26 July 2011.
  6. ↑ Miwa K, Rudivić R, Niazi GA, et al. (2010). "Silent cerebral infarction is associated with incident stroke and TIA independent of carotid intima-media thickness". Intern Med. 49 (9): 817–22. doi: 10.2169/internalmedicine.49.3211 . PMID   20453400.
  7. ↑ Stevens MC, Lehmann H, Mason KP (January 1982). "Sickle cell-Hb Lepore Boston syndrome. Uncommon differential diagnosis to homozygous sickle cell disease". Am J Dis Child. 136 (1): 19–22. doi:10.1001/archpedi.1982.03970370021004. PMID   7055103.
  8. ↑ Gupta LCPK; Kumar CH; Kumar CCS; Jaiprakash BM (2009). "Cation exchange high performance liquid chromatography for diagnosis of haemoglobinopathies" (PDF). Med J Armed Forces India. 65 (1): 33–37. doi:10.1016/s0377-1237(09)80051-8. PMC   4921438 . PMID   27408187. Archived from the original (PDF) on 11 August 2016.
  9. ↑ Almon McKusick; Stylianos E. Antonarakis (1998). Mendelian Inheritance in Man: A Catalog of Human Genes and Genetic Disorders (12th ed.). Johns Hopkins University Press. p.  849. ISBN   0-8018-5742-2.
  10. 1 2 "Haemoglobin Lepore – Anaemias – Enerca".
  11. ↑ "Α.Τ.Ε.Ι ΗΡΑΚΛΕΙΟΥ ΤΜΗΜΑ ΝΟΣΗΛΕΥΤΙΚΗΣ" (PDF). Archived from the original (PDF) on 5 November 2013.
  12. ↑ McKeown SM, Carmichael H, Markowitz RB, Kutlar A, Holley L, Kutlar F (June 2009). "Rare occurrence of Hb Lepore-Baltimore in African Americans: molecular characteristics and variations of Hb Lepores". Ann Hematol. 88 (6): 545–8. doi:10.1007/s00277-008-0631-4. PMID   18989669. S2CID   8931267.
  13. ↑ Ropero P, Murga MJ, González FA, Polo M, Benavente C, Salvador M, Villegas A (2005). "The first case of Hb E-Saskatoon associated with Hb Lepore-Baltimore found in Spain". Hemoglobin. 29 (3): 215–9. doi:10.1081/hem-200066321. PMID   16114185. S2CID   31863952.
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