2. Case Summary John a 4 year old boy ,complains of
a weakness, fatigue, and dyspnea
(labored breathing).
Parents encounter bouts of fatigue, but have never consulted a physician.
Parents are from Greece.
Significance: Greeks have agenatic predilection for certain diseases.

3. Key information pointing to diagnosis
Patient presents with anemia. Weakness, fatigue, and dyspnea are symptoms of anemia.
CBC
WBC: *10^9/L
RBC: *10^12/L LOW
HB: g/dl LOW
HCT: L/L LOW
MCVC: fL. LOW
MCH: pg LOW
MCHC: g/dl LOW
Platlets : *10^9/L
Moderate pokilocytosis.
Polychromasia and target cell.
tear drop cells.
H inclousion.
Microcytic/hypochromic
Target cells/Codocytes
CBC
LOW RBC, HB, and HCT. (Anemia)
Hypochromic/microcytic.
Peripheral Blood Smear
Polychromasia and target cells (dominant)

4. Additional lab confirming the diagnosis:
Hemoglobin electrophoresis and Iron panel.
HbA 66% LOW
HbA2 1.0%
HbF 1.0%
Hb barts 8% Abnormally present
HbH 24% Abnormally present
Serum iron 92ug/dl
TIBC 310ug/dl
Serum ferritin 88 ug/ml
Iron saturation 33%
Hemoglobin electrophoresis results Abnormal.
HbA level are low
8% Hb Barts and 24%Hb H are abnormally present .
Iron studies are Normal
Alpha thalassemia is commonly found in Mediterranian people .

5. Iron Deficiency Anemia: Iron panel normal
The diagnosis for case 1
Iron Deficiency Anemia:
Iron panel normal
Hemoglobinopathies and beta Thalassemia
Alpha chains decreased: LOW Hgb A 66% (95%_98%)
Beta and Gamma chains in excess Hgb H 24%, Hgb Barts 8%.
Hgb S, SC, C : NO Sickle cells or crystals present.
Diagnosis : Hemoglobin H Disease (alpha Thalassemia)

6. Pathophysiology of HB H Disease
Patient with deletional HB H Disease lack 3 of the alpha globin genes.
Patient with Non-deletional HB H Disease lack of 2 of alpha globin genes and 1 of the present genes is abnormal.
Gene deletion result in excess gamma and beta chains.
Excess (gamma4 tetramers) form in the fetus.
Excess (beta4 tetramer) form in adult.
HB H Disease (B4) ranges from 5 to 30% of HB in patient with the disease(24%)in this case.
HB H has a high affinity for oxygen ,resulting less O2 delivered to the tissues.

7. HB H forms an intracellular precipitate.
Precipitates make HB H RBCs more rigid leading to culling in the spleen .
HB H Disease is mainly a hemolytic disorder.
Precipitates may also cause ineffective erythropoiesis..
Peripheral blood film in HB H disease

8. Diagnostic Tests For HB H Disease
Hemoglobin electrophoresis is used to quantify and identify hemoglobin type .
High performance Liquid Chromatography can quickly separate different hemoglobins.
Brilliant cresyl blue stain can display HB H inclusions.
An inclusion body positive cell seen in Brilliant Cresyl Blue stained red cells of a α0-thalassaemia carrier. Inclusion Bodies are β4-tetramers

9. Therapy and prognosis for HB H Disease
For severe anemia : blood transformation.
Splenectomy.
Hematopoietic stem cell transplantation.
_ Require bone marrow transplant
_ Only in severe cases.
Prognosis:
Proper care reduces medical complications
Good prognosis with treatment.

10. Take Home Massage: The diagnosis is HB H (alpha thalassemia)
Typical symptoms:
- Fatigue, weakness and dyspnea
The cause of disease:
-3 alpha chain gene deletion.
Diagnosis tests:
-CBC, Iron panel, Hemoglobin electrophoresis.
Treatment :
_ Intermittent blood transfusions for sever anemia.
_ Splenectomy then bone marrow transplant in sever anemia.
_ Dietary restriction and avoiding certain medication.
Prognosis:
Prognosis is good with proper medical care.
Prevention is genetic counseling with family history.
Prenatal testing.