Hemoglobin Lepore syndrome is typically an

asymptomatic In medicine, any disease is classified asymptomatic if a patient tests as carrier for a disease or infection but experiences no symptoms. Whenever a medical condition fails to show noticeable symptoms after a diagnosis it might be considered asy ...

hemoglobinopathy Hemoglobinopathy is the medical term for a group of inherited blood disorders and diseases that primarily affect red blood cells. They are single-gene disorders and, in most cases, they are inherited as autosomal co-dominant traits. There are tw ...

, which is caused by an

autosomal recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

genetic mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitos ...

. The Hb Lepore variant, consisting of two normal

alpha globin Hemoglobin subunit alpha, Hemoglobin, alpha 1, is a hemoglobin protein that in humans is encoded by the ''HBA1'' gene. Gene The human alpha globin gene cluster located on chromosome 16 spans about 30 kb and includes seven loci: 5'- zeta - pseu ...

chains (HBA) and two delta-beta globin fusion chains which occurs due to a "crossover" between the

delta Delta commonly refers to: * Delta (letter) (Δ or δ), a letter of the Greek alphabet * River delta, at a river mouth * D ( NATO phonetic alphabet: "Delta") * Delta Air Lines, US * Delta variant of SARS-CoV-2 that causes COVID-19 Delta may also ...

(HBD) and

beta globin Hemoglobin subunit beta (beta globin, β-globin, haemoglobin beta, hemoglobin 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, hemoglobi ...

(HBB) gene loci during

meiosis Meiosis (; , since it is a reductional division) is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, such as sperm or egg cells. It involves two rounds of division that ultimately resu ...

and was first identified in the Lepore family, an Italian-American family, in 1958. 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 Electrophoresis, from Ancient Greek ἤλεκτρον (ḗlektron, "amber") and φόρησις (phórēsis, "the act of bearing"), is the motion of dispersed particles relative to a fluid under the influence of a spatially uniform electric fie ...

and

chromatographic In chemical analysis, chromatography is a laboratory technique for the separation of a mixture into its components. The mixture is dissolved in a fluid solvent (gas or liquid) called the ''mobile phase'', which carries it through a system (a ...

properties and hematological findings bear close resemblance to those of the

beta-thalassemia Beta thalassemias (β 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 cl ...

trait; a blood disorder that reduces the production of the iron-containing

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

hemoglobin Hemoglobin (haemoglobin BrE) (from the Greek word αἷμα, ''haîma'' 'blood' + Latin ''globus'' 'ball, sphere' + ''-in'') (), abbreviated Hb or Hgb, is the iron-containing oxygen-transport metalloprotein present in red blood cells (erythrocyte ...

which carries oxygen to cells and which may cause

anemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, th ...

. The

homozygous Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mo ...

state for Hb Lepore is rare. Patients of

Balkan The Balkans ( ), also known as the Balkan Peninsula, is a geographical area in southeastern Europe with various geographical and historical definitions. The region takes its name from the Balkan Mountains that stretch throughout the who ...

descent tend to have the most severe presentation of symptoms including severe

during the first five years of life. They also presented with significant

splenomegaly Splenomegaly is an enlargement of the spleen. The spleen usually lies in the left upper quadrant (LUQ) of the human abdomen. Splenomegaly is one of the four cardinal signs of ''hypersplenism'' which include: some reduction in number of circulating ...

hepatomegaly Hepatomegaly is the condition of having an enlarged liver. It is a non-specific medical sign having many causes, which can broadly be broken down into infection, hepatic tumours, or metabolic disorder. Often, hepatomegaly will present as an abdomi ...

, and skeletal abnormalities identical to those of homozygous

. The amount of Hb Lepore in the patients

blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the c ...

ranged from 8 to 30%, the remainder being

fetal hemoglobin Fetal hemoglobin, or foetal haemoglobin (also hemoglobin F, HbF, or α2γ2) 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 ...

(Hb F) which is present in minute quantities (typically<1 percent) in the

red blood cells Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek language, Greek ''erythros'' for "red" and ''k ...

of adults. Known as F- cells they are present in a small proportion of overall RBCs.

Homozygous Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mo ...

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

) and

microcytosis Microcytosis or microcythemia is a condition in which red blood cells are unusually small as measured by their mean corpuscular volume. When associated with anemia, it is known as microcytic anemia. Causes Microcytic anemia is not caused by re ...

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 A silent stroke (or asymptomatic cerebral infarction) is a stroke that does not have any outward symptoms associated with stroke, and the patient is typically unaware they have suffered a stroke. Despite not causing identifiable symptoms, a sile ...

A silent stroke is a type of

stroke A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...

that does not have any outward symptoms (

), 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 A transient ischemic attack (TIA), commonly known as a mini-stroke, is a minor stroke whose noticeable symptoms usually end in less than an hour. TIA causes the same Symptoms of stroke, symptoms associated with strokes, such as weakness or numbn ...

and major stroke in the future.

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.

Diagnosis

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

Complete blood count A complete blood count (CBC), also known as a full blood count (FBC), is a set of medical laboratory tests that provide cytometry, information about the cells in a person's blood. The CBC indicates the counts of white blood cells, red blood cell ...

(CBC) * Cation Exchange

High-performance liquid chromatography High-performance liquid chromatography (HPLC), formerly referred to as high-pressure liquid chromatography, is a technique in analytical chemistry used to separate, identify, and quantify each component in a mixture. It relies on pumps to pa ...

(CE-HPLC): a

technique used to separate and quantify various normal and abnormal hemoglobin components in blood. *

Hemoglobin electrophoresis Hemoglobin electrophoresis is a blood test that can detect different types of hemoglobin. The test can detect hemoglobin S, the form associated with sickle cell disease, as well as other abnormal types of hemoglobin, such as hemoglobin C. It can a ...

DNA analysis Genetic testing, also known as DNA testing, is used to identify changes in DNA sequence or chromosome structure. Genetic testing can also include measuring the results of genetic changes, such as RNA analysis as an output of gene expression, or ...

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. Management includes a regular course of

blood transfusion Blood transfusion is the process of transferring blood products into a person's circulation intravenously. Transfusions are used for various medical conditions to replace lost components of the blood. Early transfusions used whole blood, but mo ...

s, 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.

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.

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 Central is an adjective usually referring to being in the center of some place or (mathematical) object. Central may also refer to: Directions and generalised locations * Central Africa, a region in the centre of Africa continent, also known as ...

and

Eastern Europe Eastern Europe is a subregion of the Europe, European continent. As a largely ambiguous term, it has a wide range of geopolitical, geographical, ethnic, cultural, and socio-economic connotations. The vast majority of the region is covered by Russ ...

. The three main varieties are named for the geographical areas they were first identified in with various subtypes, the three main varieties are: *

Washington Washington commonly refers to: * Washington (state), United States * Washington, D.C., the capital of the United States ** A metonym for the federal government of the United States ** Washington metropolitan area, the metropolitan area centered o ...

(Hb Lepore Washington, also known as Hb Lepore Boston or Hb Lepore Washington-Boston); most common in

Italians , flag = , flag_caption = The national flag of Italy , population = , regions = Italy 55,551,000 , region1 = Brazil , pop1 = 25–33 million , ref1 = , region2 ...

from

Southern Italy Southern Italy ( it, Sud Italia or ) also known as ''Meridione'' or ''Mezzogiorno'' (), is a macroregion of the Italian Republic consisting of its southern half. The term ''Mezzogiorno'' today refers to regions that are associated with the peop ...

Baltimore Baltimore ( , locally: or ) is the List of municipalities in Maryland, most populous city in the U.S. state of Maryland, fourth most populous city in the Mid-Atlantic (United States), Mid-Atlantic, and List of United States cities by popula ...

(Hb Lepore Baltimore); first described in a family with

African African or Africans may refer to: * Anything from or pertaining to the continent of Africa: ** People who are native to Africa, descendants of natives of Africa, or individuals who trace their ancestry to indigenous inhabitants of Africa *** Ethn ...

ancestry; most common in people from the

Balkan countries The Balkans ( ), also known as the Balkan Peninsula, is a geographical area in southeastern Europe with various geographical and historical definitions. The region takes its name from the Balkan Mountains that stretch throughout the whol ...

Albanians The Albanians (; sq, Shqiptarët ) are an ethnic group and nation native to the Balkan Peninsula who share a common Albanian ancestry, culture, history and language. They primarily live in Albania, Kosovo, North Macedonia, Montenegro, Se ...

Croats The Croats (; hr, Hrvati ) are a South Slavic ethnic group who share a common Croatian ancestry, culture, history and language. They are also a recognized minority in a number of neighboring countries, namely Austria, the Czech Republic, G ...

Serbs The Serbs ( sr-Cyr, Срби, Srbi, ) are the most numerous South Slavic ethnic group native to the Balkans in Southeastern Europe, who share a common Serbian ancestry, culture, history and language. The majority of Serbs live in their na ...

Slovenes The Slovenes, also known as Slovenians ( sl, Slovenci ), are a South Slavic ethnic group native to Slovenia, and adjacent regions in Italy, Austria and Hungary. Slovenes share a common ancestry, culture, history and speak Slovene as their n ...

and

Romanians The Romanians ( ro, români, ; dated exonym ''Vlachs'') are a Romance languages, Romance-speaking ethnic group. Sharing a common Culture of Romania, Romanian culture and Cultural heritage, ancestry, and speaking the Romanian language, they l ...

. It has also been described in

Turks Turk or Turks may refer to: Communities and ethnic groups * Turkic peoples, a collection of ethnic groups who speak Turkic languages * Turkish people, or the Turks, a Turkic ethnic group and nation * Turkish citizen, a citizen of the Republic o ...

and in regions of

Spain , image_flag = Bandera de España.svg , image_coat = Escudo de España (mazonado).svg , national_motto = ''Plus ultra'' (Latin)(English: "Further Beyond") , national_anthem = (English: "Royal March") , i ...

and

Portugal Portugal, officially the Portuguese Republic ( pt, República Portuguesa, links=yes ), is a country whose mainland is located on the Iberian Peninsula of Southwestern Europe, and whose territory also includes the Atlantic archipelagos of ...

. A rare case of the Baltimore variety was discovered in an

African American African Americans (also referred to as Black Americans and Afro-Americans) are an ethnic group consisting of Americans with partial or total ancestry from sub-Saharan Africa. The term "African American" generally denotes descendants of ens ...

woman in the

Bronx, New York The Bronx () is a Boroughs of New York City, borough of New York City, coextensive with Bronx County, in the U.S. state, state of New York (state), New York. It is south of Westchester County, New York, Westchester County; north and east of the ...

and dubbed Hn Lepore-Bronx and another variety was discovered in the city of

Saskatoon Saskatoon () is the largest city in the Provinces and territories of Canada, Canadian province of Saskatchewan. It straddles a bend in the South Saskatchewan River in the central region of the province. It is located along the Trans-Canada Hig ...

Saskatchewan Saskatchewan ( ; ) is a Provinces and territories of Canada, province in Western Canada, western Canada, bordered on the west by Alberta, on the north by the Northwest Territories, on the east by Manitoba, to the northeast by Nunavut, and on t ...

, Canada and dubbed Hb E-Lepore Saskatoon * Hollandia (Hb Lepore Hollandia); identified in

Papua New Guinea Papua New Guinea (abbreviated PNG; , ; tpi, Papua Niugini; ho, Papua Niu Gini), officially the Independent State of Papua New Guinea ( tpi, Independen Stet bilong Papua Niugini; ho, Independen Stet bilong Papua Niu Gini), is a country i ...

and

Bangladesh Bangladesh (}, ), officially the People's Republic of Bangladesh, is a country in South Asia. It is the eighth-most populous country in the world, with a population exceeding 165 million people in an area of . Bangladesh is among the mos ...

References

{{DEFAULTSORT:Hemoglobin Lepore Syndrome Genetic disorders with OMIM but no gene Disorders of globin and globulin proteins Red blood cell disorders Hemoglobins Syndromes