HEMOGLOBINOPATHIES AND PORPHYRIAS

Hemoglobin solubulity test screening test (dithionate tube testing)

Forms tachoids or precipitates
Principle: rbc are lysed with saponin. Sodium dithionite removes oxygen from the test
envi. If no ox it cuases polymerization (hbg. Will precipitate causing tachoids or crystal)
if turbid there is presence of hbg. S

Sodium Metabisulfite- deoxygenized (screening test)

Sickle cells also known as drepanocyte

ACIDIC CITRINE AGAR- ACIDIC PH

Saponin- lysing agent

Dithionite- reducing agent

Sickle cell- drepanocyte

-normocytic, normochromic

Dithionate tube testing- screening test

porphyria is most often used to refer to the hereditary conditions that impair production of
protoporphyrin
congenital erythropoietic porphyria (CEP), even in utero as nonimmune hydrops fetalis.

CONGENITAL ERYTHROPOIETIC PORPHYRIA (CEP)

- Günther’s disease, is an autosomal recessive disorder.
- due to the markedly deficient, but not absent, activity of URO synthase and the
resultant accumulation of URO I and COPRO I isomers.

ERYTHROPOIETIC PROTOPORPHYRIA (EPP)

- inherited disorder resulting from the deficient activity of ferrochelatase (FECH).
- EPP is the most common erythropoietic porphyria in children and, after PCT, the
second most common porphyria in adults.
EPP patients have FECH activities as low as 15–25% of normal in lymphocytes and cultured
fibroblasts
X-LINKED ERYTHROPOIETIC PROTOPORPHYRIA (XLP)
- To date, four ALAS2 mutations, three deletions of one to four bases, and one novel
nonsense mutation have been described, which markedly increase ALA synthase 2
activity and cause XLP
Oral beta-carotene

Hemoglobinopathy refers to a disease state (opathy) involving the hemoglobin (Hb) molecule.
- The most common genetic diseases, affecting approximately 7% of the world’s
population.
- All hemoglobinopathies result from a genetic mutation in one or more genes that affect
hemoglobin synthesis

Point Mutations

 Most common type of genetic mutation occurring in the hemoglobinopathies

 Involves the replacement of one nucleotide
 Results in amino acid substitution
 Reading frame remains intact
 1178 out of 1275 known variants caused by point mutations
Deletions

 Involves the removal of nucleotides

 Typically disrupts reading frame
 Leads to nullification of globin chain synthesis
 58 variants result from deletions
Insertions

 Involves the addition of nucleotides

 Reading frame usually remains intact
 May affect hemoglobin structure and function
 28 variants result from insertions

Chain Extentions

 Occur when the stop codon is mutated

Gene Fusions

 Occurs when two genes break

Sickle cell disease

-chromosome 11, amino acid substation at position 6 of beta globin chain

- life span 17 days

Mild to moderate, normocytic and normochromic- hgb. C

THALASSEMIA

COOLEY’S ANEMIA(BETA THALASSEMIA) (major thalassemia)

- Mycrocytic hypochromic anemia

- Anysocytocis
- Target cells
- Reticulocytosis
- Nucleated red cells
Alpha and zeta- chromosome 16

Gamma, beta, delta, epsilon- chromosome 11

Clinical manifestation of thalassemia stem:

Microcytic and hypochromic rbc

Thalassemia is considered as quantitative

- Defects in alpha or beta chain

Fetal life predominant haemoglobin- hgb.

 4 gamma chains is called hgb. Bart

 4 beta chains is called hgb. H
 Hgb bart and H are High affinity in oxygen.
Thalassemia minor- also called as beta thalassemia trait

Thalassemia major- 2 defects in chains

Major thalassemia- both genes are deleted

Minor thalassemia- 1 gene is deleted

Hydrops fetalis- no alpha chain or all alpha chains are deleted

- For infants they will not die immediately because of, the baby can still survive because
the hgb are present gower1, Portland no gower 2 because alpha is deleted
 MICROCYTIC HYPOCHROMIC MORPHOLOGY (ATIS)

ANEMIA OF CHRONIC INFLAMMATION

THALASSEMIA

IDA

SIDEROBLASTIC

Supravital stain with hgb H has dots (pitted golf ball appearance)

Thalassemia

- Iron is present, everything is decreased or normal except for TIBC

Hemoglobinopathy- qualitative there are amino acid substition

Thalassemia- quantitative defect of globulin portions

Decrease rate of synthesis in globin chain