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HEREDITARY ANEMIAS

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HEREDITARY ANEMIAS PROF. SAMIYA NAEEMULLAH Diplomate American Board of Pediatrics FAAP, FCPS Head of Pediatrics Department Islamic International Medical College – PowerPoint PPT presentation

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Title: HEREDITARY ANEMIAS


1
HEREDITARY ANEMIAS
  • PROF. SAMIYA NAEEMULLAH
  • Diplomate American Board of Pediatrics
  • FAAP, FCPS
  • Head of Pediatrics Department
  • Islamic International Medical College

2
ANEMIA
  • Defined as HB level below normal range
  • Varies with age and sex of the individual
  • Neonate Hb lt 14 g/dl
  • 1-12 months Hb lt10 g/dl
  • 1- 12 years Hb lt 11 g/dl

3
  • IMPAIRED RED CELL PRODUCTION
  • Congenital Red cell aplasia
  • Diamond Blackfan Anemia
  • Fanconi Anemia

4
INCREASED RED CELL DESTRUCTION
  • Hemolytic Anemias

RED CELL MEMBRANE DISORDERS Hereditary
Spherocytosis RED CELL ENZYME
DISORDER Glucose 6 phosphate dehydrogenase
deficiency (G6PD) Hemoglobinopathies Sickle cell
disease Thalassemia
5
LEARNING OBJECTIVES
  • Discuss the etiology of different types of
    hereditary anemias?
  • Differentiate between cell defects, enzymatic
    defects and hemoglobinopathies
  • Be able to distinguish the morphology of
    different hemolytic anemias
  • Discuss clinical features of sickle cell disease
    and Thalassemia Major
  • Correlate clinical features with pathophysiology
    of the disease

6
DIAMOND BLACKFAN ANEMIA
  • Etiology
  • Autosomal dominant 15
  • Autosomal recessive 15
  • Spradic 80
  • FH 20

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ANEMIA
9
CONGENITAL ANOMALIES
Short stature
10
DIAGNOSIS
  • Low Hb macrocyte
  • Low reticulocyte Count
  • Normal bilirubin
  • Absent red cell precussors on narrow

11
INHERITED APLASTIC ANEMIAS
  • Reduction or absence of all three main line in
    bone marrow leading to peripheral blood
    pancytopenia

12
FANCONIS ANEMIA
  • Short stature
  • Abnormal radii thumbs
  • Renal manifestation
  • Pigmented skin lesion
  • Increased chromosomal breakage of peripheral
    blood lymphocytes

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  • Schwachman Diamond Syndrome
  • Autosomal Recessive disorder
  • Bone marrow failure
  • Pancreatic exocrine failure
  • Skeletal abnormalities

19
RED CELL MEMBRANE DISORDERS
  • Hereditary spherocytosis
  • Hereditary elliptocytosis

20
HEREDITARY SPHEROCYTOSIS
  • Autosomal dominant
  • No F/H in 25 cases
  • Defect in genes for the skeletal proteins of the
    red cells membrane spectrin, ankyrin and band 3
    red cell losses part of its membrane passing
    through spleen

21
  • ?in surface to volume ratio causes the cells to
    become spheroidal.
  • Less deformable than normal RBS
  • Destruction in micro vasculature of the spleen

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  • Jaundice at birth
  • Anemia
  • Mild to moderate splenomegaly
  • Aplastic crises
  • Gall stones

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ENZYME DEFECTS
  • Glucose 6 phosphate dehydrogenase (G6PD)
    deficiency
  • Commonest red cell enzymopathy effecting over 100
    million people world wide
  • G6PD in red cell essential for preventing
  • Oxidative damage to red cells
  • So cell lacking the enzyme are suseptible to
    oxidant induced hemolysis

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  • Etiology with inherited as X linked effects males
  • G6PD activity in ? in Red cells
  • Mostly in old cells

28
X LINKED INHERITANCE
29
CLINICALLY
  • Neonatal Jaundice
  • Acute hemolysis precipitected by
  • Drugs
  • Infection
  • Naphthalene in moth balls
  • Intravascular hemolysis
  • Fever, malaise, dark colored urine

30
HEMOGLOBINOPATHIES
  • These are red blood cell disorders which cause
    hemolytic anemia because of
  • Reduced or absent production of Hb A(? ?
    thalassemia)
  • Production of abnormal Hb e.g. sickle cell
    disease

31
BETA THALASSEMIA AUTOSOMAL RECESSIVE
  • Inherited disorder characterized by absence or
    decreased synthesis of beta globin chain of
    hemoglobin

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  • Normal Fetal Hb at different ages
  • At birth 70
  • 5 weeks 55
  • 4 months 10
  • 5 month 5
  • At one year (lt 2)

34
  • HETEROZYOUS SATE
  • Thalassemia Minor
  • One normal betaglobin chain gene and one
    beta-thalassemia gene
  • HOMOZYGOUS
  • Thalassemia Intermedia
  • 2 ? Thalassemia genes
  • Thalassemia Major
  • 2 Beta thalassemia genes

35
PATHOPHYSIOLOGY
  • Beta Thalassemia minor
  • Most Common
  • Failure of one gene coding for beta chain
  • Alpha chain production normal
  • Alpha chain available combine with beta chain
  • ? Hb A levels

36
  • Excess alpha chain stimulates production of
    delta chain Hb A2 ?
  • Still excess alpha chains switches off gamma
    chain production does not function correctly. And
    rate of gamma chain production is greater than in
    normal adult so ? amount of Hb F.

37
  • HbF
  • Poor oxygen deliverer and high affinity for O2
  • Only functional Hb present is A2
  • Hypoxia
  • Erythropoetin
  • Stimulated marrow to maximum
  • Extremedullary hematopaiesis
  • Splenomegaly

38
CLINICAL MANIFESTATIONS
  • Thalassemia Minor
  • The Growth Development is normal
  • Mild anemia Hb 10 mg./dl

39
  • Thalassemia Intermedia
  • Symptomatic by 2 4 yrs of age
  • Mod anemia
  • Thalassemic facies
  • Growth failure
  • Hepatosplenomegaly
  • Jaundice

40
THALASSEMIA MAJOR
  • DETROIT PEDIATRICIAN
  • 1925 THOMAS COOLEY (Cooley Anemia)
  • Profound anemia
  • Splenomegaly
  • Bony deformities
  • Greek word Thalasa SEA Blood

41
  • Universally fatal disease
  • Is now converted into chronic illness

42
INCIDENCE
  • 3 of worlds population carry Thalassemia gene
  • PAKISTAN
  • Carrier rate 4-5
  • Pathans 5.8
  • Total No of patients 50,000-60,000
  • 5000 6000 children are born each year

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THALASSEMIA MAJOR
  • Born normal at birth
  • Starts getting pale,fussy,irritable
  • Starts refusing feeds

46
INFANT
47
CHILD
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CLINICAL FEATURE
  • Bossing of skull
  • Maxillary overgrowth
  • Long face
  • Hepatosplenomegaly
  • Bones become thin
  • Fractures may occur
  • Heart failure

49
ADOLESCENT
50
COMPLICATIONS
  • Iron Overload
  • Darkening of skin(Iron stimulated melanin)
  • Cardiomyopathy
  • Endocrinopathies
  • Infections (Hepatitis A,B,C,Malaria,HIV)
  • Failure to thrive
  • Antibody formation(10)Alloantibodies

51
LAB DIAGNOSIS
  • Complete Blood Count
  • RBC Morphology
  • Hemoglobin Electrophoresis
  • Serum Iron Ferritin levels
  • Imaging Study

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IRON OVERLOAD LEAD TO
  • Liver fibrosis
  • Cardiomyopathy
  • Dysfunction of endocrine organs
  • Diabetes
  • Clinical Organ dysfunction
  • Well transfused patient dies by 10-25 yrs if not
    chelated

56
ADULT
  • Fertility
  • Ability to Reproduce and bare children
  • Reduce fertility due to iron overload
  • Control iron levels
  • Pregnancy monitoring, reproductive assistance and
    perinotologist
  • 40 cases reported

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KEY MESSAGES
  • Screen the Population
  • Get The Blood Tested
  • Detect Thalessemia Traits
  • Prevent them from marrying other thalassemia
    traits
  • Counselling
  • Help the children families with Thalassemia

59
? THALASSEMIA
  • Healthy infants have four ? globin genes.
  • The manifestation of ? thalassemic syndromes
    depend on the number of functional ? globlin
    chains
  • Deletion of 4 ? globin chains
  • Hb Barts Hydrops fetalis
  • Fetal anemia edema, ascities
  • Fetus dies in utero or within hours of delivery

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  • Deletion of three ? globin genes
  • (HbH disease)
  • Mild moderate anemia
  • Deletion of one or two ? globin chains
  • ? thalassemia trait
  • Asymptomic
  • Anemia is mild or absent

62
SICKLE CELL DISEASE HbSS
  • Commonest genetic disorders in UK in 2000 births
  • Blacks from tropical Africa
  • Etiology
  • Point mutation in codon 6 of ? globin chain which
    causes change in aminoacid encoded from
  • Glutamine to Valine

63
FORMS
  • Sickle cell anemia
  • SC disease
  • Sickle ? thalassemia

64
SICKLE CELL ANEMIA HbSS
  • Patients are hemozygons for Hbs i.e. virtually
    all their Hb is Hbs
  • No HbA no normal ? genes

65
SC DISEASE
  • Affected children inherit
  • Hbs one parent
  • HbC- other parent

66
SICKLE ? THALASSEMIA
  • Affected children inherit
  • Hbs from one parent
  • ? thalassemia trait 2nd parent
  • No normal ?-globin genes and most patients can
    make no Hb A so can transmit Hb S to their
    offspring
  • Symptoms are similar to those with sickle cell
    anemia.

67
SICKLE TRAIT
  • Inheritance of HbS from one parent
  • Normal ? - globin gene other parent
  • 40 of the Hb is HbS
  • Carriers of HbS
  • Asymptomatic

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CLINICAL MANIFESTATIONS
  • Anemia 6 8 gm/d
  • Jaundice
  • VASO - OCCLUSIVE CRISES
  • Late infancy
  • Hand foot syndrome
  • Bones of limbs spine
  • Cerebral pulmonary infarction
  • Acute stroke

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PRECIPITATING FACTORS
  • Exposure to cold
  • Dehydration
  • Excessive exercise
  • Stress
  • Hypoxia
  • Infection

74
ACUTE ANEMIA
  • Hemolytic crisis
  • Associated with infection
  • Aplastic crisis
  • By parvo virus infection
  • complete or temporary caestion of red blood cell
    production
  • Sequestration crisis
  • Sudden splenic enlargement
  • Abdominal pain
  • Circulatory collapse

75
INFECTIONS
  • Susceptibily to infections as pneumococcus
    hemophitus influenzae
  • Increased incidence of Bone infection by
    salmonella
  • Chronic sickling microinfarction in spleen

76
  • Neonatal Diagnosis at birth guthrie test
  • Prenatal diagnosis by chorionic villus sampling
    at the end of 1sttrimester

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MANAGEMENT STEPS
  • Regular red cell transfusions
  • Chelation therapy
  • Growth monitoring and follow up
  • Management of complications
  • Psychosocial support

79
MANAGEMENT STEPS
  • Splenectomy
  • Bone marrow transplantation
  • Cord blood transplantation
  • Drugs stimulating gamma chains
  • Gene therapy
  • Prevention and antenatal diagnosis

80
MULTI DISCIPLINARY APPROACH
  • Social worker
  • Parents
  • Patient
  • Pediatrician
  • Hematologist
  • Gynecologist
  • Physician
  • Surgeon
  • Ophthalmologist
  • E NT Specialist
  • Lab technician
  • Psychologist
  • psychiatrist
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