This document discusses β-thalassemia, a genetic blood disorder caused by mutations in the β-globin gene resulting in reduced or absent β-chain production and hemoglobin synthesis. It is characterized by microcytic hypochromic anemia and is most common around the Mediterranean sea. The degree of β-chain deficiency determines the severity from β° (no β-chains) to β++ (more β-chains). Clinical manifestations include anemia, jaundice, hepatosplenomegaly, skeletal abnormalities, and heart failure. Management involves blood transfusions, chelation therapy, and folic acid supplementation.

2. Ahmed Salah
Eldin (42)
Ahmed Adel
Emara (49)
Ahmed Salah
Eldin Maarof
(43)
Ahmed Adel
Fouad (48)
Ahmed Tarek
Abd Elnabi
(45)
Ahmed Adel
Abd Abd
Elrahman (46)

3. This is a group characterized by an MCV (<76 fL) and MCHC (<32g/dL)
below the normal range or an increased microcytic and hypochromic
subpopulation. These changes result from a decreased production of
hemoglobin.

6. β - Most common around meditranian sea.
In β - thalassemia there is impaired production of β -chain due to
mutation of one gene "heterozygous" or both genes homozygous".
According to degree of β – chain deficiency β thalassmia is divided
into:
• Βo no β-chain synthesis no HbA only HbF and HbA2.
• β+ little β-chain synthesis, so HbA is scanty and more HbF and
HbA2.
• β++ more β chain synthesis → thalassemia intermediate.

7. • Age of presentation usually start at the age
of 6-12 months.
• Clinical evidence of haemolytic
anemia, pallor, jaundice
hepatosplenomegaly mongoloid facies.
• Crisis:
– Haemolytic crisis precipitated by
infection by parvovirus B19.
– Megaloblastic crisis due to folic acid
deficiency
• Cardiomegally and hemic murmur.
• Growth retardation
• short stature
• delayed puberty due to endocrinal
disturbances.

8. Clinical Picture
• Increase
susceptabilty to
infection
• Iron overload
(haemochromatosis)
• Anemic heart failure.
Hypersplenism.
• Pathological
fracture.
• Complications of
repeated blood
transfusion: e.g.
hepatitis C.

9. • Hypochromic microcytic anemia with
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anisocytosis, poikilocytosis, target cell.
Reticulocytic count: increased nucleated RBCs
in peripheral blood.
Increase serum iron with decrease serum iron
binding capacity.
Hb electrophoresis: (increase HbF).
B.M. examinations show erythroid
hyperplasia.
X-ray bone of skull → hair on end apearance due
to widening of diploid space.
-Cardiomegaly
may be present.
Evident diagnosis:
Genotyping or P.C.R. (Polymerase Chain
Reaction) to detect the mutation on
-Weak mutation → thalassemia intermedia
Strong mutation → thalassemia major

11. (Heterozygous ) It may be asymptomatic or symptomatic:
-Mild anemia (Hb 9-11 g/dl) accentuated during infections.
-Anemia is microcytic hypochromic and does not respond to iron
therapy.
-No jaundice or other signs of hemolysis.
-Hb electrophoresis: Hb A is predominant, Hb A2 is increase
( 4%), Hb F may be slightly increase.

12. : Affects 2-10 % of homozygous patients and is characterized by:
• Patients have higher ability to produce β –chain and high production of γ-chains.
• Genetic, morphologic and biochemical features: like β-thalassemia major.
• Anemia is milder (Hg level 7-10g/dl).
• Pallor, jaundice, facial bony changes, splenomegaly and hepatomegaly are present.
• No growth retardation and no hypogonadism.
Treatment: -Blood transfusion is usually not needed and given only when required.
-Decrease iron absorption from GIT (e.g. drink a cup of tea after each meal).
-Chelation therapy and folic acid supplementation.

13. •
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Hb E is the second most common Hb variant.
The clinical course of E β-thalassemia is punctuated by acute and chronic
complications that may cause serious morbidity and mortality.
The marked expansion of erythropoiesis is responsible for much of the pathology of
the disease, including:
1. hepatosplenomegaly
2. extramedullary hematopoietic masses,
3. growth retardation,
4. delayed sexual maturation
5. bone deformities.
6. Cardiopulmonary disease is the most common cause of death in Hb E βThalassemia.

15. Definetion:
decreased total iron body content enough to diminish
erythropoiesis.

16. 1-Dietary factors->Lack of breast feeding with unsupplemented
cow milk or formula and delayed weaning-Substances that
diminish the absorption of iron e.g. phytates...
2-Storage defect->iron deficient mother- preterm child-LBWIUGR.
3-Infection->reduces appetite, absorption-increases
loss(vomiting..)-depresses BM.
4-Hemorrhage->chronic blood loss e.g. hookworm infestationsmilk protein intolerance.
5-Hemosiderinuria, hemoglobinuria, and pulmonary
hemosiderosis->loss of iron.
6-Malabsorption of iron->Prolonged achlorhydria.

17. Clinical Picture:
In addition to general manifestations
of anemia there are decrease
mental concentration, atrophy of
mucosa,anorexia,immune
suppretion,muscular weakness… .
Investigations:
Serum ferritin is low, Decreased
serum iron, increased iron binding
capacity, Microcytosis, hypochromi
a, anisocytosis, Increased red cell
distribution width (RDW).

18. Treatment:
 Prophylactic->adequate fe supply for pregnantsupplementation starting from 4th month.
 Curative-> 1-6 mg/kg/day of elemental iron.
2-Diet adjustments- increase amount of Fe in the diet.
3-Transfusion in severe cases Hb<6.
4-parentral is not preferred.

19. Atransferrinemia
Definition:
Atranferrinemia is a genetic disorder wherein the plasma protein that carries iron
(transferrin) in the blood stream is lacking.
Pathophysiology:
This disease is characterized by a microcytic hypochromic anemia, and an iron
deposition in the heart and liver.
This iron damage to the heart can also be the cause of heart
failure while anemia is typically hypochromic and microcytic.
Death may occur due to heart failure or pneumonia.

20. Clinical Picture:
Iron overload occurs mainly in the
liver, eye, pancreas, thyroid, kidney and
joints, leading to moderate to serious symptoms of
liver and eye, arthropathy and hypothyroidism.
Treatment:
plasma infusion of transferrin->If this therapy is
repeated once or twice monthly, the patient becomes
hematologically normal within a few months.

22. •
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A heterogeneous group of disorders
Variable red cell hypochromia, anemia
The ringed sideroblasts should total 10% or more of the
nucleated red cell
Failure to utilize iron properly during heme synthesis in the
mitochondria

23. Hereditary/congenital SA
• Primary X-linked
• Primary autosomal
Acquired
• Primary idiopathic
• Secondary acquired
• Drugs: isoniazid, chloramphenicol
• Toxins: alcohol (chronic abuse), lead
• Copper deficiency
• Zinc excess

24. Defect in mitochondrial function
and heme synthesis
mutant ALAS
enzymes
Ferrochelatase
defects
copro-oxidase
defects

25. •History of failure of growth
•Family history of mitochondrial disease and anemia
•General symptoms of anemia,
•Vital signs – Hypothermia
•Skin - Photosensitivity (porphyria)
•Cardiovascular – Fatigue
•Respiratory – Dyspnea
•Musculoskeletal - Muscular weakness
•Genitourinary - Pink staining of diapers from porphyrins in
urine

26. • Complete blood count (CBC),
• peripheral smear,
• iron studies,
• bone marrow aspiration and biopsy.
Microcytosis
• variable degree of anemia
• Serum iron and ferritin are elevated
• TIBC reduced.
 partially treated iron deficiency anemia.
 acquired disorders associated with the
presence of excess ringed sideroblasts
in the marrow

27. • Infants developing in the womb of a woman, who have elevated
blood lead level, are susceptible to lead poisoning. There is also a
risk as the baby comes closer to full term, as the woman is more
likely to have a premature, or with a low birth weight.
• Children are more at risk for lead poisoning because their smaller
bodies are in a continuous state of growth and development.
• The classic signs and symptoms in children are loss of appetite,
abdominal pain, vomiting, weight loss, constipation, anemia,
kidney failure, irritability, lethargy, learning disabilities, and
behavioral problems.

29. 
Copper deficiency is a very rare
hematological and neurological disorder.
Copper deficiency is only seen in
malnourished premature babies and in
patients receiving long-term parenteral
nutrition with inadequate copper
supplementation.
 Copper is absorbed almost exclusively
during the last trimester and deficiency in
a premature infant may be accentuated if
the child is given copper-deficient feeds
such as cows’ milk at an early age.

30. •
Surgery : Bariatric surgery, such as gastric bypass surgery.The
disruption of the intestines and stomach from the surgery can cause
absorption difficulties.
• Zinc Toxicity
• Hereditary Disorders : Menkes disease is a hereditary condition
caused by a defective gene involved with the metabolism of copper
in the body. Menkes disease is usually a fatal disease with most
children dying within the first ten years of life.
• ​Other : It is rarely suggested that excess iron supplementation
causes copper deficiency myelopathy. celiac disease, probably due
to malabsorption in the intestines.Still, a large percentage, around
20%, of cases have unknown causes.

31. •
Iron Transportation: Hephaestin is a copper containing ferroxidase
enzyme located in the duodenal muscosa that oxidizes iron and
facilitates its transfer across the basolateral membrane into circulation.
• Ceruloplasmin,This enzyme is required to mobilize iron from the
reticuloendothelial cell to plasma. It also oxidizes iron from its ferrous
state to the ferric form that is required for iron binding.
• Impairment in these copper dependent enzymes that transport iron
may cause the secondary iron deficiency anemia.
• Another speculation for the cause of anemia is involving the
mitochondrial enzyme cytochrome c oxidase. The lower rate of the
enzyme might cause the excess iron to clump, giving the heme an
unusual pattern known as ringed sideroblastic anemia cells.

32. Hematological Findings:
• tiredness, fatigue, and light headedness.
These are all common symptoms of
anemia.
• All types of anemia including microcytic
, macrocytic and normocytic manifest.
Around half of the patients displayed
“leukopenia".
• In addition to leukopenia, many patients
are deficient in neutrophils (neutropenia).
• Usually prolonged copper deficiency has
to persist to manifest thrombocytopenia.

33. Neurological presentation:
• Myelopathy : difficulty in walking caused by sensory
ataxia due to dorsal column dysfunction or degeneration
of the spinal cord
• Peripheral neuropathy : numbness or tingling that can start
in the extremities .
• Optic neuropathy : signs of vision and ​color loss. The
vision is usually lost in the peripheral views of the eye.

34. • The diagnosis is made by demonstrating a low serum copper and
ceruloplasmin.
• Examination of the marrow reveals decreased granulocyte
maturation, vacuolization of red blood cell precursors, and ringed
sideroblastic cells are present .
• Neutropenia has become a hematological hallmark, enabling
physicians to investigate copper deficiency as a diagnosis.

36.  Lead poisoning is a medical condition
caused by increased levels of the heavy
metal lead in the body.
 Routes of exposure to lead includes
contaminated air, water, soil, food,and
consumer products. Occupational exposure
is a common cause of lead poisoning in
adults.

37. • Infants developing in the
womb of a woman, who have
elevated blood lead level, are
susceptible to lead poisoning.
There is also a risk to have a
premature, or with a low birth
weight.
• Children are more at risk for
lead poisoning because their
smaller bodies are in a
continuous state of growth
and development.

38. •
One of the main causes for the pathology of lead is that it
interferes with the activity of an essential enzyme called deltaaminolevulinic acid dehydratase, or ALAD, which is important in
the biosynthesis of heme, the cofactor found in hemoglobin.
• Lead also inhibits the enzyme ferrochelatase, another enzyme
involved in the formation of heme.
• Lead's interference with heme synthesis results in production of
zinc protoporphyrin and the development of anemia.
• Another effect of lead's interference with heme synthesis is the
buildup of heme precursors, such as aminolevulinic acid, which
may be directly or indirectly harmful to neurons.

39. • The main tool in diagnosing and assessing the severity of lead
poisoning is laboratory analysis of the blood lead level (BLL).
• Blood film examination may reveal basophilic stippling of red
blood cells (dots in red blood cells visible through a microscope),
as well as the changes normally associated with iron-deficiency
anemia (microcytosis and hypochromasia).

40. • Anemia is the commonest hematologic manifestation of
systemic disease and is the result of a number of contributing
factors. It occurs in patients with a variety ​of chronic
inflammatory and malignant conditions and can be
complicated by bleeding, immune phenomena, nutritional
deficiencies and other organ- or disease-specific features.

42.  The anemia is usually mild, 2–3 g/dL below the lower normal limit for
a given individual, and nonprogressive with the severity being related
to the severity of the disease process.
•
Associated features indicative of chronic inflammation such as
neutrophilia, thrombocytosis and rouleaux formation may be present.
• In addition to hematologic tests, there may be low albumin, elevated
fibrinogen and γ-globulin​ concentrations.
 In anemia of chronic disease without iron deficiency, ferritin levels
should be normal or high, reflecting the fact that iron is stored within
cells. In iron deficiency anemia ferritin should be low.
 Examination of the bone marrow to look for the absence or presence
of iron, or a trial of iron can provide more definitive diagnoses.

44. • Vitamin b6 deficiency results in inadequate heme production and, thus,
lowers concentrations of hemoglobin in red blood cells. This condition,
called microcytic, hypochromic anemia, interferes with the ability of red
blood cells to deliver oxygen to tissues and impairs their ability to produce
ATP via anaerobic metabolism.

45. Clinical picture:
• Cheilosis.
• Glossitis.
• Stomatitis .
• Fatigue.

46. • Vitamin B6 deficiency is rare when food is abundant, however,
the damaging effect of high temperature on Vitamin B6 was
not well understood, and Vitamin B6 added to infant formula
was destroyed during heat processing, thus many formula-fed
infants developed Vitamin B6 deficiency. This unfortunate
“epidemic” of Vitamin B6 caused serious complications such
as seizures and convulsions. Manufacturing procedures have
changed so that infant formula now contains sufficient
amounts of this essential nutrient.