What are the different types of thalassemia. How does thalassemia affect the human body. What are the symptoms of alpha and beta thalassemia. Can thalassemia be diagnosed and treated effectively.

The Basics of Thalassemia: A Genetic Blood Disorder

Thalassemia is a group of inherited blood disorders that affect the production of hemoglobin, the protein in red blood cells responsible for carrying oxygen throughout the body. This condition results in the formation of abnormal red blood cells, leading to anemia and various health complications.

To comprehend thalassemia’s impact on the human body, it’s crucial to understand the structure of hemoglobin. Hemoglobin consists of two proteins: alpha and beta. When the body doesn’t produce enough of either protein, red blood cells cannot form properly, resulting in insufficient oxygen transport.

Key Facts About Thalassemia

• Thalassemia is a genetic disorder
• It affects hemoglobin production
• Results in anemia that begins in early childhood
• Can be classified into alpha and beta thalassemia

Alpha Thalassemia: Types and Severity

Alpha thalassemia occurs when there’s insufficient production of alpha protein in hemoglobin. This type of thalassemia is prevalent in Africa, the Middle East, India, Southeast Asia, southern China, and occasionally in the Mediterranean region.

Four Types of Alpha Thalassemia

1. Silent Carrier State
2. Hemoglobin Constant Spring
3. Alpha Thalassemia Trait (Mild Alpha Thalassemia)
4. Hemoglobin H Disease

How does the severity of alpha thalassemia vary across these types? The severity ranges from mild to severe, with the Silent Carrier State causing no noticeable health problems, while Hemoglobin H Disease can lead to serious complications.

Silent Carrier State and Hemoglobin Constant Spring

The Silent Carrier State is characterized by a minimal lack of alpha protein, allowing hemoglobin to function normally. It’s called “silent” due to its difficulty in detection. Similarly, Hemoglobin Constant Spring, an unusual form of the Silent Carrier State, typically doesn’t cause health issues.

Alpha Thalassemia Trait and Hemoglobin H Disease

Alpha Thalassemia Trait results in smaller red blood cells and mild anemia, often mistaken for iron deficiency. Hemoglobin H Disease, on the other hand, causes severe anemia and serious health problems such as an enlarged spleen, bone deformities, and fatigue.

Severe Forms of Alpha Thalassemia

There are three severe forms of alpha thalassemia that warrant special attention due to their significant impact on health:

• Hemoglobin H-Constant Spring
• Homozygous Constant Spring
• Alpha Thalassemia Major (Hemoglobin Bart’s Hydrops Fetalis)

What sets these severe forms apart from milder types of alpha thalassemia? These conditions involve a greater deficiency in alpha protein production, leading to more severe anemia and associated health complications.

Hemoglobin H-Constant Spring and Homozygous Constant Spring

Hemoglobin H-Constant Spring is more severe than Hemoglobin H disease, with patients experiencing more frequent spleen enlargement and viral infections. Homozygous Constant Spring, while generally less severe, still presents challenges similar to Hemoglobin H disease.

Alpha Thalassemia Major

Alpha Thalassemia Major is the most severe form, where no alpha genes are present in the individual’s DNA. This condition leads to the formation of abnormal hemoglobin called hemoglobin Barts. While extremely serious, treatment and survival are possible with in utero blood transfusions and lifelong medical care.

Beta Thalassemia: Understanding Its Types and Prevalence

Beta thalassemia occurs when there’s insufficient production of beta protein in hemoglobin. This type of thalassemia is commonly found in people of Mediterranean descent, as well as in the Arabian Peninsula, Iran, Africa, Southeast Asia, and southern China.

Three Types of Beta Thalassemia

1. Thalassemia Minor (Thalassemia Trait)
2. Thalassemia Intermedia
3. Thalassemia Major

How do these types of beta thalassemia differ in their severity and impact on health? The severity ranges from mild in Thalassemia Minor to severe in Thalassemia Major, with Thalassemia Intermedia falling in between.

Thalassemia Minor (Thalassemia Trait)

Thalassemia Minor is characterized by a slight deficiency in beta protein, which doesn’t significantly affect hemoglobin function. Individuals with this condition are carriers of the thalassemia trait and typically experience no health problems beyond possible mild anemia.

Why is Thalassemia Minor often misdiagnosed? The small red blood cells associated with this condition are frequently mistaken for iron-deficiency anemia, leading to unnecessary iron supplement prescriptions.

Diagnosis and Treatment of Thalassemia

Accurate diagnosis of thalassemia is crucial for proper management and treatment. Various diagnostic methods are employed to identify the specific type and severity of thalassemia.

Diagnostic Methods for Thalassemia

• Complete Blood Count (CBC)
• Hemoglobin Electrophoresis
• Genetic Testing
• Family History Analysis

How is thalassemia diagnosed in its early stages? Early diagnosis often involves a combination of blood tests, genetic analysis, and family history evaluation. Newborn screening programs in some regions can detect certain types of thalassemia shortly after birth.

Treatment Options for Thalassemia

Treatment for thalassemia varies depending on the type and severity of the condition. Options may include:

1. Regular Blood Transfusions
2. Iron Chelation Therapy
3. Folic Acid Supplements
4. Bone Marrow Transplantation
5. Gene Therapy (Emerging Treatment)

What are the primary goals of thalassemia treatment? The main objectives are to manage anemia, prevent complications, and improve quality of life. In severe cases, such as beta thalassemia major, regular blood transfusions are often necessary to maintain adequate hemoglobin levels.

Living with Thalassemia: Challenges and Management

Living with thalassemia presents unique challenges for patients and their families. However, with proper management and support, many individuals with thalassemia can lead fulfilling lives.

Common Challenges Faced by Thalassemia Patients

• Chronic Anemia
• Iron Overload
• Growth and Development Issues
• Bone Problems
• Enlarged Spleen
• Increased Risk of Infections

How can individuals with thalassemia manage their condition effectively? Effective management involves adhering to treatment plans, regular medical check-ups, maintaining a healthy lifestyle, and staying informed about the latest developments in thalassemia care.

Psychological and Social Aspects

Living with a chronic condition like thalassemia can have psychological and social impacts. Support from family, friends, and support groups can play a crucial role in helping individuals cope with the challenges of thalassemia.

Research and Future Prospects in Thalassemia Treatment

Ongoing research in the field of thalassemia aims to improve treatment options and potentially find a cure for this genetic disorder. Several promising avenues of research are currently being explored.

Emerging Treatments and Research Areas

• Gene Therapy
• Stem Cell Transplantation
• Novel Iron Chelation Agents
• Fetal Hemoglobin Induction
• CRISPR Gene Editing

What potential breakthroughs are on the horizon for thalassemia treatment? Gene therapy and CRISPR gene editing show particular promise in potentially correcting the genetic defects responsible for thalassemia. Clinical trials are ongoing to assess the safety and efficacy of these innovative approaches.

The Role of Clinical Trials

Clinical trials play a crucial role in advancing thalassemia treatment. They provide opportunities for patients to access new therapies and contribute to the development of improved treatment options.

How can patients participate in thalassemia clinical trials? Interested individuals should consult with their healthcare providers about ongoing trials and eligibility criteria. Organizations like the Cooley’s Anemia Foundation often provide information about current research opportunities.

Genetic Counseling and Thalassemia Prevention

Genetic counseling plays a vital role in thalassemia prevention and family planning for individuals at risk of passing on the disorder.

The Importance of Genetic Counseling

• Helps individuals understand their risk of having a child with thalassemia
• Provides information about prenatal testing options
• Offers support in making informed decisions about family planning
• Assists in interpreting genetic test results

When should individuals consider genetic counseling for thalassemia? Genetic counseling is recommended for couples planning to have children, especially if they have a family history of thalassemia or belong to ethnic groups with a higher prevalence of the disorder.

Prenatal Testing and Screening

Prenatal testing can detect thalassemia in a developing fetus. This information allows parents to make informed decisions and prepare for the potential needs of a child with thalassemia.

What prenatal testing options are available for thalassemia? Common prenatal tests include chorionic villus sampling (CVS) and amniocentesis. These tests can determine if a fetus has thalassemia and, if so, the specific type and severity.

Global Impact and Awareness of Thalassemia

Thalassemia affects populations worldwide, with varying prevalence in different regions. Raising awareness about the condition is crucial for improving diagnosis, treatment, and support for affected individuals.

Thalassemia Around the World

• Mediterranean Region: High prevalence of beta thalassemia
• Southeast Asia: High prevalence of alpha thalassemia
• Middle East: Significant presence of both alpha and beta thalassemia
• Africa: Various types of thalassemia present

How does the global distribution of thalassemia impact healthcare strategies? The varying prevalence of thalassemia across regions necessitates tailored screening programs, treatment approaches, and public health initiatives to address the specific needs of affected populations.

Awareness Initiatives and Support Organizations

Numerous organizations worldwide are dedicated to raising awareness about thalassemia, supporting patients and families, and advancing research. These include:

• Thalassaemia International Federation (TIF)
• Cooley’s Anemia Foundation
• Thalassemia Support Foundation
• Various national thalassemia associations

What role do these organizations play in the thalassemia community? These organizations provide educational resources, patient support services, advocacy for improved care, and funding for research initiatives aimed at enhancing the lives of individuals affected by thalassemia.

In conclusion, understanding the complexities of thalassemia, its various types, and its impact on individuals and communities is crucial for improving diagnosis, treatment, and support for those affected by this genetic blood disorder. Ongoing research and global awareness efforts continue to drive progress in thalassemia care, offering hope for better outcomes and potentially curative treatments in the future.

About Thalassemia – The Cooley’s Anemia Foundation

Thalassemia: A Basic Description

Thalassemia is the name of a group of genetic blood disorders. To understand how thalassemia affects the human body, you must first understand a little about how blood is made.

Hemoglobin is the oxygen-carrying component of the red blood cells. It consists of two different proteins, an alpha and a beta. If the body doesn’t produce enough of either of these two proteins, the red blood cells do not form properly and cannot carry sufficient oxygen. The result is anemia that begins in early childhood and lasts throughout life.

Since thalassemia is not a single disorder but a group of related disorders that affect the human body in similar ways, it is important to understand the differences between the various types of thalassemia.

Alpha Thalassemia

People whose hemoglobin does not produce enough alpha protein have alpha thalassemia. It is commonly found in Africa, the Middle East, India, Southeast Asia, southern China, and occasionally the Mediterranean region.

There are four types of alpha thalassemia that range from mild to severe in their effect on the body.

Silent Carrier State. This condition generally causes no health problems because the lack of alpha protein is so small that the hemoglobin functions normally. It is called “silent carrier” because of how difficult it is to detect. Silent carrier state is “diagnosed” by deduction when an apparently normal individual has a child with hemoglobin H disease or alpha thalassemia trait.

Hemoglobin Constant Spring. This is an unusual form of Silent Carrier state that is caused by a mutation of the alpha globin. It is called Constant Spring after the region of Jamaica in which it was discovered. As in silent carrier state, an individual with this condition usually experiences no related health problems.

Alpha Thalassemia Trait or Mild Alpha Thalassemia. In this condition, the lack of alpha protein is somewhat greater. Patients with this condition have smaller red blood cells and a mild anemia, although many patients do not experience symptoms. However, physicians often mistake mild alpha thalassemia for iron deficiency anemia and prescribe iron supplements that have no effect on the anemia.

Hemoglobin H Disease. In this condition, the lack of alpha protein is great enough to cause severe anemia and serious health problems such as an enlarged spleen, bone deformities and fatigue. It is named for the abnormal hemoglobin H (created by the remaining beta globin) that destroys red blood cells.

Hemoglobin H-Constant Spring. This condition is more severe than hemoglobin H disease. Individuals with this condition tend to have a more severe anemia and suffer more frequently from enlargement of the spleen and viral infections.

Homozygous Constant Spring. This condition is a variation of hemoglobin H-Constant Spring that occurs when two Constant Spring carriers pass their genes on to their child (as opposed to hemoglobin H Constant Spring, in which one parent is a Constant Spring Carrier and the other a carrier of alpha thalassemia trait). This condition is generally less severe than hemoglobin H Constant Spring and more similar to hemoglobin H disease.

Alpha Thalassemia Major (Hemoglobin Bart’s Hydrops Fetalis). In this condition, there are no alpha genes in the individual’s DNA, which causes the gamma globins produced by the fetus to form an abnormal hemoglobin called hemoglobin Barts. While alpha thalassemia major is an extremely serious condition, treatment and survival is possible with in utero blood transfusions. Individuals born with alpha thalassemia major are treated with lifelong blood transfusions and other medical care. (UCSF Benioff Children’s Hospital has created two brochures on alpha thalassemia major and treatment options, including a new clinical trial exploring in utero stem cell transplantation. The parents brochure is here and the healthcare providers brochure is here.)

Beta Thalassemia

People whose hemoglobin does not produce enough beta protein have beta thalassemia. It is found in people of Mediterranean descent, such as Italians and Greeks, and is also found in the Arabian Peninsula, Iran, Africa, Southeast Asia and southern China.

There are three types of beta thalassemia that also range from mild to severe in their effect on the body.

Thalassemia Minor or Thalassemia Trait. In this condition, the lack of beta protein is not great enough to cause problems in the normal functioning of the hemoglobin. A person with this condition simply carries the genetic trait for thalassemia and will usually experience no health problems other than a possible mild anemia. As in mild alpha thalassemia, physicians often mistake the small red blood cells of the person with beta thalassemia minor as a sign of iron-deficiency anemia and incorrectly prescribe iron supplements.

Thalassemia Intermedia. In this condition the lack of beta protein in the hemoglobin is great enough to cause a moderately severe anemia and significant health problems, including bone deformities and enlargement of the spleen. However, there is a wide range in the clinical severity of this condition, and the borderline between thalassemia intermedia and the most severe form, thalassemia major, can be confusing. The deciding factor seems to be the amount of blood transfusions required by the patient. The more dependent the patient is on blood transfusions, the more likely he or she is to be classified as thalassemia major. Generally speaking, patients with thalassemia intermedia need blood transfusions to improve their quality of life, but not in order to survive.

Thalassemia Major or Cooley’s Anemia. This is the most severe form of beta thalassemia in which the complete lack of beta protein in the hemoglobin causes a life-threatening anemia that requires regular blood transfusions and extensive ongoing medical care. These extensive, lifelong blood transfusions lead to iron-overload which must be treated with chelation therapy to prevent early death from organ failure.

Other Forms of Thalassemia

In addition to the alpha and beta thalassemias, there are other related disorders that occur when the gene for alpha or beta thalassemia combines with an abnormal or mutant gene.

E Beta Thalassemia. Hemoglobin E is one of the most common abnormal hemoglobins. It is usually found in people of Southeast Asian ancestry, such as Cambodians, Vietnamese and Thai. When combined with beta thalassemia, hemoglobin E produces E beta thalassemia, a moderately severe anemia which is similar in symptoms to beta thalassemia intermedia.

Sickle Beta Thalassemia. This condition is caused by a combination of beta thalassemia and hemoglobin S, the abnormal hemoglobin found in people with sickle cell disease. It is commonly found in people of Mediterranean ancestry, such as Italians, Greeks and Turks. The condition varies according to the amount of normal beta globin produced by the beta gene. When no beta globin is produced by the beta gene, the condition is almost identical with sickle cell disease. The more beta globin produced by the beta gene, the less severe the condition.

Downloadable Brochures on Thalassemia and Its Complications

Downloadable pdf brochures about thalassemia and various complications associated with the disorder can be accessed by clicking on the links below.

1. The COVID-19 Pandemic and Thalassemia
   • The COVID-19 Pandemic and Haemoglobin Disorders
   • Health and Nutrition Short Guide for COVID-19 Pandemic
   • FAQs Regarding the Impact of the COVID-19 Pandemic on Individuals with Thalassemia
   • COVID-19 and Thalassemia: A Position Statement of the International Thalassaemia Federation
2. Thalassemia Information
   • An Introduction to Beta-Thalassemia Major
   • An Introduction to Beta-Thalassemia Intermedia (English, Spanish)
   • What is Hemoglobin E (English, Bengali, Burmese, Cambodian, Chinese, Hmong, Karen, Laotian, Thai, Vietnamese)
   • What is Hemoglobin H (English, Burmese, Cambodian, Chinese, Spanish, Vietnamese)
   • Thalassaemia from ‘A’ to ‘Z’: A Comprehensive e-Glossary for Patients with Thalassaemia (created by the Thalassaemia International Federation (TIF))
3. Thalassemia Trait Information
   • Why Should You Care About Thalassemia? (English, Chinese)
   • Have You Been Tested for Alpha Thalassemia Trait? (English, Cambodian, Chinese, French, Hmong, Karen, Spanish, Vietnamese)
   • Have You Been Tested For Beta Thalassemia Trait? (English, Arabic, Bengali, Cambodian, Chinese, Greek, Hindi, Karen, Spanish, Swahili, Thai, Urdu, Vietnamese)
   • What is Thalassemia Trait? (English only, English/Chinese (bilingual))
   • What Should I Know About Thalassemia? (English, Chinese, Karen)
4. Thalassemia-Related Complications
   • Pulmonary Hypertension in Thalassemia
   • Transfusion Issues in Thalassemia
   • Low Bone Mass in Thalassemia
   • Cardiac Issues in Thalassemia
   • Diabetes and Thalassemia
   • Hepatitis and Liver Issues in Thalassemia
   • Thalassemia and the Spleen
   • Fertility and Pregnancy in Thalassemia
5. Thalassemia-Related Tests and Procedures/Comprehensive Care
   • Non-Invasive Iron Measurements
   • What to Expect When You Go For a MRI for Heart or Liver Iron
   • Comprehensive Care Checklist for Thalassemia
   • Thalassemia Treatment Centers
   • Information on Gene Therapy and Gene Editing
   • Gene Therapy in B-thalassemia
   • Bone Marrow Transplantation in B-thalassemia (TIF Publication)
6. Nutrition in Thalassemia
   • Zinc – An Informational Pamphlet for Patients with Thalassemia – created by UCSF Benioff Children’s Hospital Oakland
   • Zinc – An Informational Pamphlet for Care Providers of Individuals with Thalassemia – created by UCSF Benioff Children’s Hospital Oakland
7. Guides/Toolkits for Those Living with Thalassemia
   • A Guide to Living with Thalassemia
   • School Toolkit for People with Transfusion-Dependent Thalassemia
8. Thalassemia Standards of Care Guidelines
   • Thalassemia Standards of Care Guidelines- Children’s Hospital & Research Center Oakland
   • TIF 2021 Guidelines for the Management of Transfusion-Dependent Thalassaemia
   • TIF 2017 Guidelines for the Management of Non-Transfusion-Dependent Thalassaemia
9. Thalassemia Management Checklists
   • Monitoring Deferasirox Therapy
   • Guidelines for Managing Transfusion Therapy for Thalassemia
   • Monitoring of Iron Overload in Transfusion-Dependent Thalassemia (TDT)
10. Thalassemia Materials for Children
    • All About Thalassemia – created by TIF (English, Arabic, Bengali, Chinese, Malay, Myanmar, Sinhala, Spanish, Turkish)
    • Cooley’s Anemia Foundation Storybook
11. Information about the Cooley’s Anemia Foundation (CAF)
    • How to Register Online with CAF
    • CAF New Patient Registration Brochures
    • CAF: Leading the Fight Against Thalassemia
    • What is Cooley’s Anemia and the Cooley’s Anemia Foundation?
12. Health Messaging Postcards
    • Know Your Numbers!
    • She Has Thalassemia and Still Runs Half-Marathons
    • You Are Your Child’s Best Advocate
    • When Iron Gets Out of Balance
    • Being Adherent to Thalassemia Treatment Has a Big Pay-off
    • Don’t Wait for Your Heart to Tell You About Iron
    • Planning a Trip This Summer?
    • Getting Your Child Ready for Back-to-School?
    • Flu Season Is Coming
    • Flu Season is Here
    • Testing for Low Bone Mass Helps Prevent Fractures
    • Exercise is Important for Optimal Health
    • Pregnancy Health Message
    • Temporarily Suspending Chelation During Fever
    • Have You Chelated Today?
    • It’s Never Too Late to Start Being Physically Active
    • Partner with Your Healthcare Team to Take Charge of Your Health
    • Keep Calm and Chelate
    • Chelation Therapy Gave Me New Life

Hypochromic microcytic anemia with iron overload: MedlinePlus Genetics

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Description

Hypochromic microcytic anemia with iron overload is a condition that impairs the normal transport of iron in cells. Iron is an essential component of hemoglobin, which is the substance that red blood cells use to carry oxygen to cells and tissues throughout the body. In this condition, red blood cells cannot access iron in the blood, so there is a decrease of red blood cell production (anemia) that is apparent at birth. The red blood cells that are produced are abnormally small (microcytic) and pale (hypochromic). Hypochromic microcytic anemia with iron overload can lead to pale skin (pallor), tiredness (fatigue), and slow growth.

In hypochromic microcytic anemia with iron overload, the iron that is not used by red blood cells accumulates in the liver, which can impair its function over time. The liver problems typically become apparent in adolescence or early adulthood.

Frequency

Hypochromic microcytic anemia with iron overload is likely a rare disorder; at least five affected families have been reported in the scientific literature.

Causes

Mutations in the SLC11A2 gene cause hypochromic microcytic anemia with iron overload. The SLC11A2 gene provides instructions for making a protein called divalent metal transporter 1 (DMT1). The DMT1 protein is found in all tissues, where its primary role is to transport positively charged iron atoms (ions) within cells. In a section of the small intestine called the duodenum, the DMT1 protein is located within finger-like projections called microvilli. These projections absorb nutrients from food as it passes through the intestine and then release them into the bloodstream. In all other cells, including immature red blood cells called erythroblasts, DMT1 is located in the membrane of endosomes, which are specialized compartments that are formed at the cell surface to carry proteins and other molecules to their destinations within the cell. DMT1 transports iron from the endosomes to the cytoplasm so it can be used by the cell.

SLC11A2 gene mutations lead to reduced production of the DMT1 protein, decreased protein function, or impaired ability of the protein to get to the correct location in cells. In erythroblasts, a shortage of DMT1 protein diminishes the amount of iron transported within cells to attach to hemoglobin. As a result, the development of healthy red blood cells is impaired, leading to a shortage of these cells. In the duodenum, a shortage of DMT1 protein decreases iron absorption. To compensate, cells increase production of functional DMT1 protein, which increases iron absorption. Because the red blood cells cannot use the iron that is absorbed, it accumulates in the liver, eventually impairing liver function. The lack of involvement of other tissues in hypochromic microcytic anemia with iron overload is likely because these tissues have other ways to transport iron.

Inheritance

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Other Names for This Condition

• Microcytic anemia and hepatic iron overload
• Microcytic anemia with liver iron overload

Additional Information & Resources

Genetic Testing Information

• Genetic Testing Registry: Anemia, hypochromic microcytic, with iron overload 1

Genetic and Rare Diseases Information Center

• Hypochromic microcytic anemia with iron overload

Patient Support and Advocacy Resources

• Disease InfoSearch
• National Organization for Rare Disorders (NORD)

Catalog of Genes and Diseases from OMIM

• ANEMIA, HYPOCHROMIC MICROCYTIC, WITH IRON OVERLOAD 1

Scientific Articles on PubMed

• PubMed

References

• Bardou-Jacquet E, Island ML, Jouanolle AM, Detivaud L, Fatih N, Ropert M,
  Brissot E, Mosser A, Maisonneuve H, Brissot P, Loreal O. A novel N491S mutation
  in the human SLC11A2 gene impairs protein trafficking and in association with the
  G212V mutation leads to microcytic anemia and liver iron overload. Blood Cells
  Mol Dis. 2011 Dec 15;47(4):243-8. doi: 10.1016/j.bcmd.2011.07.004. Epub 2011 Aug
  26. Citation on PubMed
• Beaumont C, Delaunay J, Hetet G, Grandchamp B, de Montalembert M, Tchernia G.
  Two new human DMT1 gene mutations in a patient with microcytic anemia, low
  ferritinemia, and liver iron overload. Blood. 2006 May 15;107(10):4168-70. doi:
  10.1182/blood-2005-10-4269. Epub 2006 Jan 26. Citation on PubMed
• Iolascon A, d’Apolito M, Servedio V, Cimmino F, Piga A, Camaschella C.
  Microcytic anemia and hepatic iron overload in a child with compound heterozygous
  mutations in DMT1 (SCL11A2). Blood. 2006 Jan 1;107(1):349-54. doi:
  10.1182/blood-2005-06-2477. Epub 2005 Sep 13. Citation on PubMed
• Iolascon A, De Falco L. Mutations in the gene encoding DMT1: clinical
  presentation and treatment. Semin Hematol. 2009 Oct;46(4):358-70. doi:
  10.1053/j.seminhematol.2009.06.005. Citation on PubMed
• Lam-Yuk-Tseung S, Camaschella C, Iolascon A, Gros P. A novel R416C mutation in
  human DMT1 (SLC11A2) displays pleiotropic effects on function and causes
  microcytic anemia and hepatic iron overload. Blood Cells Mol Dis. 2006
  May-Jun;36(3):347-54. doi: 10.1016/j.bcmd.2006.01.011. Epub 2006 Apr 3. Citation on PubMed

causes, symptoms, types, diagnosis, treatment

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This disease is treated by Hematologist

The information provided on this page should not be used for self-treatment or self-diagnosis. If you suspect a disease, you should seek help from a qualified specialist. Only your doctor can diagnose and prescribe treatment.

Article content:

• Varieties
• Causes of development
• Clinical picture
• Diagnostics
• Treatment tactics
• Prognosis and prevention

What is microcytic anemia?

Microcytic anemia is a condition in which smaller red blood cells circulate in the blood than in a healthy person.
human Source:
Anemia. Saraeva N.O. Educational
allowance for students. Irkutsk State Medical University of the Federal Agency for
health care and social development. 2009. pp.70-78. Small red blood cells contain
less hemoglobin, which means they carry a small amount of oxygen. Against this background, oxygen
tissue starvation – hypoxia, which causes the symptoms of microcytic anemia. The disease is congenital
and acquired, the tactics of treatment depend on the cause.

Varieties

All microcytic anemia due to development are classified into two large groups – congenital and acquired. Congenital microcytic anemias include:

• alpha thalassemia;
• beta thalassemia;
• sideroblastic anemia.

Acquired forms:

• iron-deficient;
• sideropenic;
• anemia of chronic disease.

All varieties of anemia are characterized by a decrease in the volume of erythrocytes, a change in their shape.

The classification includes three degrees of disease severity:

• mild – hemoglobin 90-110 g/l;
• medium – hemoglobin 70-90 g/l;
• severe – hemoglobin less than 70 g / l.

Causes of development

Thalassemias are congenital forms of microcytic anemia in which hemoglobin synthesis is disturbed. There are alpha and beta forms of the disease. The most common in Africa, South Asia, the countries of the Mediterranean region. The cause of thalassemia is mutations in the genes responsible for the synthesis of hemoglobin Source:
Molecular basis of hereditary microcytic anemia due to defects in iron absorption or heme synthesis. Iolascon A, De Falco L, Beaumont S. Hematology. 2009. pp. 395-408.

Genetic mutations also cause sideroblastic anemia. At the same time, the bone marrow uses an insufficient amount of iron for the synthesis of hemoglobin, even if its reserves in the body are not depleted. A small amount of red blood cells and hemoglobin enters the blood – such anemia is called microcytic hypochromic anemia.

Causes of acquired microcytic anemia:

• malnutrition, in which an insufficient amount of iron enters the body;
• accelerated consumption of iron during inflammation, infections;
• deficiency of vitamins B6 and C;
• heavy metal salt poisoning;
• long-term use of hemotoxic drugs;
• chronic blood loss;
• myelodysplastic syndrome;
• renal and hepatic insufficiency.

Clinical picture

The symptoms of congenital microcytic anemia are similar, and their severity depends on the characteristics of the genetic mutation, the ratio of normal and defective hemoglobin. In patients with minor genetic abnormalities, anemia is asymptomatic. Violations in all the genes responsible for the synthesis of hemoglobin lead to intrauterine death of the fetus, since the blood is not at all able to carry oxygen.

Clinical picture of thalassemia in early childhood:

• moon face;
• saddle bridge;
• tower skull;
• large upper jaw;
• enlargement of the liver and spleen.

Against the background of thalassemia, lesions of the liver, spleen and heart develop. Patients are at high risk of infectious diseases.

Anemia syndrome is characteristic of all types of microcytosis:

• chronic fatigue;
• pale and dry skin;
• hair loss, brittleness and deformity of nails;
• attacks of vertigo;
• episodes of loss of consciousness.

Clinical sideroblastic anemia consists of the actual anemic syndrome and signs of iron accumulation in the tissues:

• enlarged liver and spleen;
• gradual development of liver cirrhosis;
• heart enlargement;
• arrhythmias, the formation of heart failure;
• high risk of male and female infertility.

Iron deficiency anemia is acquired in nature, occurs due to low intake of iron in the body, its rapid consumption or malabsorption in the intestine. Specific manifestations of IDA:

• abnormal taste preferences;
• impaired sense of smell;
• goosebumps.

Anemia of chronic diseases is a symptom that occurs with infections, autoimmune and oncological pathologies, kidney damage. At the beginning of development, anemia has a normocytic character, that is, red blood cells in the blood of normal size and shape. Gradually, there is a violation of iron metabolism, and anemia becomes microcytic. Symptoms consist of manifestations of an anemic syndrome and signs of the underlying disease. Specific manifestations:

• weight loss;
• prolonged subfebrile condition;
• pain syndrome.

Examination for microcytic anemia is aimed at finding the cause of the disease, determining the severity of anemia, and assessing the prognosis. Diagnostics includes the following tests and studies:

• general clinical blood tests;
• determination of the amount of iron in blood serum;
• study of ferritin reserves;
• ultrasound examination of the abdominal organs, kidneys;
• bone marrow puncture followed by histological examination Source:
  Anemic syndrome: differential diagnosis and treatment. Budnikova N.V., Arkhipova S.L., Kalinina N.Yu. Textbook for students studying in the specialty “Medicine”. 2013. p.74.

Patients with suspected congenital origin of anemia should consult a hematologist, geneticist.

Laboratory signs of all types of microcytic anemia are similar:

• decrease in hemoglobin less than 115 g/l;
• decrease in color index less than 0.85;
• microcytosis – reduction in the size of erythrocytes;
• young forms of erythrocytes in peripheral blood;
• increased serum iron, ferritin;
• myeloid hyperplasia on bone marrow examination.

Treatment tactics

Treatment of microcytic anemia depends on its form. General principles of treatment:

• influence on the cause of the disease;
• correction of blood parameters;
• symptomatic treatment.

Mild, asymptomatic thalassemia does not require treatment. With clinically expressed forms, only pathogenetic and symptomatic treatment is possible, which begins already from the birth of a child:

• red blood cell transfusion;
• administration of chelating agents to bind excess iron Source:
  Microcytosis/Microcytic anemia. Kamashella K., Brugnara K.N. 2022.;
• taking glucocorticoids in hemolytic crisis;
• taking folic acid and vitamin B12;
• removal of the spleen with its rapid growth.

Treatment of acquired sideroblastic anemia:

• influence on the cause – treatment of the underlying disease, withdrawal of medications taken, exclusion of harmful factors at work;
• administration of chelating agents to bind excess iron;
• taking vitamin B6;
• taking folic acid;
• treatment with hepatoprotectors, antioxidants, cardiac agents.

The treatment of iron deficiency anemia includes:

• dietary modification with the inclusion in the diet of products that provide replenishment of iron reserves;
• treatment of gastrointestinal disorders that impair iron absorption;
• detection and elimination of sources of chronic bleeding – hemorrhoids, anal fissure, intestinal inflammation;
• replenishment of iron deficiency by taking iron-containing preparations;
• taking folic acid, vitamin C.

The treatment of anemia of chronic disease is to treat the underlying pathology that caused the anemia. With a pronounced decrease in hemoglobin, iron and folic acid preparations are indicated.

The prognosis for mild forms of thalassemia is favorable. In severe forms with severe symptoms, patients rarely survive even to a young age. Prevention of thalassemia consists in carefully planning pregnancy or refusing to have children in couples where one or both partners are carriers of defective genes. Source:
Microcytic hypochromic anemia. Chaudhry H.S., Casarla M.R. Stat Pearls Publishing. 2022..

The prognosis for congenital sideroblastic anemia is uncertain. In a severe course of the disease, multiple organ failure is quickly formed, patients die. Acquired forms of sideroblastic anemia have a more favorable prognosis and are easier to treat. Prevention is possible only in relation to acquired forms, it consists in maintaining a healthy lifestyle, timely treatment of diseases provoking anemia.

The prognosis for iron deficiency anemia is favorable in most cases. Adequate correction of nutrition and course intake of iron preparations lead to complete recovery. Prevention of IDA consists in a balanced diet, timely detection and treatment of diseases of the digestive system.

The prognosis for anemia of chronic disease depends on the causative pathology. Anemia itself poses less of a threat to health than the underlying disease.

• Anemia. Saraeva N.O. Textbook for students. Irkutsk State Medical University of the Federal Agency for Health and Social Development. 2009. pp.70-78
• Anemia syndrome: differential diagnosis and treatment. Budnikova N.V., Arkhipova S.L., Kalinina N.Yu. Textbook for students studying in the specialty “Medicine”. 2013. p.74
• Molecular basis of hereditary microcytic anemia due to defects in iron absorption or heme synthesis. Iolascon A, De Falco L, Beaumont S. Hematology. 2009. p.395-408
• Microcytosis/Microcytic anemia. Kamashella K., Brugnara K.N. 2022.
• Microcytic hypochromic anemia. Chaudhry H.S., Casarla M.R. Stat Pearls Publishing. 2022.

Article published on : 1/31/2023
Last updated : 2/21/2023

See also

Sideroblastic anemia

Iron deficiency anemia

Hemolytic anemia

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Diamond-Blackfan anemia.

What is Diamond Blackfan Anemia?

IMPORTANT
The information in this section should not be used for self-diagnosis or self-treatment. In case of pain or other exacerbation of the disease, only the attending physician should prescribe diagnostic tests. For diagnosis and proper treatment, you should contact your doctor.

Diamond-Blackfan anemia is a hereditary form of red cell aplasia with a reliably unexplored type of inheritance (it is assumed that an autosomal dominant type of inheritance occurs in a quarter of patients). Symptoms of the disease are anemic manifestations that occur, as a rule, during the first year of life – pallor, weakness, fatigue, a decrease in the number of red blood cells in the blood. Diagnosis is made on the basis of data from a general blood test, a study of the level of erythropoietins, a biopsy and microscopy of the bone marrow, in a quarter of cases a genetic study is informative. Treatment is carried out with the help of blood transfusions, glucocorticosteroids.

ICD-10

D61.0 Constitutional aplastic anemia. Blackfan-Diamond Syndrome.

• Causes
• Pathogenesis
• Symptoms of anemia
• Diagnostics
• Treatment of anemia Diamond-Blackfan
• Forecast
• Prices for treatment

General

Diamond-Blackfan anemia (hereditary partial red cell aplasia) is a genetic lesion of the blood system, in which the formation of red blood cells is impaired. The name of the pathology was given by the names of doctors who, at 19In 1938, four children with symptoms of severe anemia of a hereditary nature were jointly examined.

This condition is very rare, about 500 cases have been reliably described to date. It is estimated that the incidence of Diamond-Blackfan anemia is about 4-6:1000000, both boys and girls are equally affected. The discrepancy between the number of proven cases and the calculated incidence is explained by the fact that a certain proportion of patients are mistakenly diagnosed with either erythromyeloblastic leukemia or acquired forms of partial red cell aplasia. The most common form of the disease is inherited in an autosomal dominant manner, but this accounts for only 25% of all cases, while there are no data yet on the remaining variants.

Diamond-Blackfan anemia

Causes

The immediate cause of a quarter of cases of Diamond-Blackfan anemia is a mutation in the RPS19 gene located on chromosome 19, which codes for the important ribosomal protein S19. The latter is part of the small (40S) subunit of the human ribosome. This mutation is inherited in an autosomal dominant manner with an incidence of 6 cases per million people. In other cases, mutations of other genes were found, but they are somehow associated with ribosomal proteins – these are the genes RPS7, RPS24, RPL5, RPL32A and a number of others.

The prevalence of such mutations, the nature of their inheritance, the proportion in the total number of patients with Diamond-Blackfan anemia, their impact on the prognosis and outcome of the pathology at the moment remains the object of study by geneticists. Also of interest is the question of why mutations in the genes of ribosomal proteins affect erythropoiesis and have almost no effect on other hematopoietic lineages.

Pathogenesis

There are several theories trying to explain the inhibition of the formation of red blood cells in the red bone marrow. The most common causes of Diamond-Blackfan anemia are defects in the microenvironment of erythrocyte progenitor cells, their internal abnormalities, suppression by the immune system, or humoral factors that stop the maturation of erythroblasts. None of the theories has received reliable and unambiguous confirmation to date.

In this disease, a steady decrease in erythroid units is observed in the red bone marrow, and in about a third of cases this process begins during fetal development, which makes it possible to diagnose Diamond-Blackfan anemia immediately after birth. Accordingly, the number of erythrocytes released into the blood begins to decrease, erythroblasts accumulate in the bone marrow, which can be misleading (such changes are characteristic of leukemia). At the same time, in infants, the level of fetal hemoglobin may not decrease, so this indicator is not considered diagnostic in the case of Diamond-Blackfan anemia. There is a compensatory increase in the level of erythropoietins in the blood, but in this case they are not able to increase the rate of formation of red blood cells. Ultimately, severe anemia develops.

Symptoms of anemia

Anemia symptoms come to the fore in Diamond-Blackfen syndrome – pallor, weakness of the child, malnutrition often develops in infants, and there is a lack of weight. In about half of the patients, in addition to blood disorders, a number of physical abnormalities also occur – microcephaly, hypertelorism, ptosis of the eyelids, micrognathia. Anomalies of the skeleton are possible – an increase in the size of the shoulder blades and hands, the absence of some fingers, a delay in the growth of bone tissue. In some cases, violations such as “cleft lip” are possible.

The organs of vision are also affected – strabismus, glaucoma, cataracts develop. Many of these symptoms occur at an early age and are exacerbated by severe anemia, so timely treatment can significantly reduce or even eliminate many of them.

Unlike transient and acquired anemia, Diamond-Blackfer syndrome slightly affects the functioning of the liver and spleen – their noticeable increase can occur only in the final stages of the disease or as a result of complications of blood transfusion therapy.

Diagnostics

When examining a child with Diamond-Blackfan anemia, pallor of the skin, cyanosis of the mucous membranes is determined, venous vessels are visible on the head. Physical abnormalities associated with the disease (microcephaly, hypertelorism, and others) can also be observed, and weighing often reveals a lack of body weight. Laboratory diagnostic methods include:

• Blood tests. KLA shows a picture of normochromic anemia, often macrocytic in nature, a sharp decrease in the number of reticulocytes. In some cases, granulocytopenia and thrombocytopenia are observed, but this cannot serve as a reliable diagnostic criterion for Diamond-Blackfan anemia. A biochemical blood test revealed a sharp increase in the level of erythropoietin.
• Bone marrow biopsy. Microscopic examination of a bone marrow biopsy revealed a generally normocellular type with a pronounced decrease in erythroid cells. At the same time, in some forms of Diamond-Blackfan anemia, erythroblasts can accumulate in the bone marrow, which often leads to an erroneous diagnosis of acute myelogenous leukemia.
• Genodiagnostika. Modern genetics by direct sequence sequencing determines mutations in only one gene associated with Diamond-Blackfan anemia – RPS19. Using this diagnostic method, gene mutations are detected only in 25-30% of cases of a clinically diagnosed disease.

Treatment of Diamond-Blackfan anemia

With severe anemia, blood transfusions or red blood cell transfusions are indicated to compensate for the life-threatening red blood cell deficiency. In some cases, blood transfusion may be required repeatedly – for example, in the absence of the effect of glucocorticosteroid therapy. In such situations, it is necessary to take measures in relation to the prevention of damage to the liver and spleen by excess iron and other post-transfusion complications – for example, prescribe chelation therapy with deferoxamine.

The main drugs for the treatment of Diamond-Blackfan anemia are glucocorticosteroids (prednisolone, methylprednisolone and others). Therapy begins with increased (shock) dosages of drugs orally, then gradually reducing them to the level of a maintenance dose – while at the same time the hemoglobin level should increase and the blood picture improves (reticulocytes appear in the bloodstream, the number of macrocytes decreases).

Depending on the dynamics of the disease, glucocorticosteroid therapy is performed using two main schemes – in the pulse therapy mode (up to 7 days of taking high doses, followed by a two to three week break) and maintenance therapy with daily intake of small amounts of glucocorticosteroids. The choice of one or another scheme depends on the reaction of the patient’s body to drugs, the presence and severity of side effects, the effectiveness of treatment. Several cases of treatment of Diamond-Blackfan anemia with a positive outcome by bone marrow transplantation from a close relative have been described.

Forecast

The prognosis of Diamond-Blackfan anemia is largely uncertain due to a poor understanding of the processes that lead to its development. An extensive study, during which the life histories of more than 200 patients were studied, revealed that almost a quarter of children who were treated with blood transfusions and the appointment of glucocorticosteroids, even before adolescence, spontaneous remission occurred with the restoration of adequate hemoglobin levels. At the same time, more than half of the children remained dependent on both blood transfusions and the use of methylprednisolone after adolescence. The remaining 25% of patients died in childhood, despite all the therapeutic measures taken.

In many ways, the prognosis is affected by the presence or absence of concomitant physical abnormalities and the degree of their severity. Treatment with growth factors, iron preparations, and other traditional anemia remedies is ineffective and can further increase the burden on the liver and spleen.

You can share your medical history, what helped you in the treatment of Diamond-Blackfan anemia.

Sources

1. Aplastic anemia in children / V.A. Kuvshinnikov, S.G. Shenets. – 2014.
2. federal clinical guidelines for the diagnosis and treatment of Diamond-Blackfan anemia in children. – 2015.
3. Diamond-Blackfan anemia: a model of a translational approach to understanding diseases in humans/ Vlahos A. Blank L. Lipton J. M.// Russian Journal of Pediatric Hematology and Oncology. – 2014.
4. This article was prepared based on the materials of the site: https://www.krasotaimedicina.ru/

IMPORTANT
Information from this section cannot be used for self-diagnosis and self-treatment.