PORPHYRIAS,

HEMOGLOBINOPATHIES,
and THALASSEMIAS
BY KMPARRILLA,RMT
PORPHYRIAS
Impaired production of heme.
May be acquired or hereditary
Heriditary: Primary caused by
enzyme specific deficiency

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PORPHYRIAS: ACQUIRED
1. Lead Poisoning
Lead inhibits pyrimidine 5’-nucleotidase

Impaired mental development

Peripheral neuropathy
Abdominal cramping & vomiting
Seizure

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PORPHYRIAS: ACQUIRED
2. Porphyria cutanea tarda
May be acquired or inherited
Clinical feature: Photosensitivity
Exacerbating factors:
◦Alcohol
◦Hepatic injury
◦Iron overload

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PORPHYRIAS: HEREDITARY
1.Acute intermittent porphyria
2.Congenital erythropoietic porphyria
3.Hereditary coproporphyria
4.Variegate porphyria
5.Erythropoietic protoporphyria
6.Porphyria cutanea tarda
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PORPHYRIAS: HEREDITARY
1.Congenital erythropoietic porphyria

Enzyme deficient: Uroporphyrinogen III synthase

Clinical features: photosensitive ; hemolytic anemia
Labtest: normal Protoporphyrin (RBC,urine,feces)
markedly increased in Uroporphyrin
minimally increased in Coproporphyrin
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PORPHYRIAS: HEREDITARY
2. Erythropoietic protoporphyria

Enzyme deficient: Ferrochelatase

Clinical features: photosensitive ; mild anemia
Labtest: markedly increased Protoporphyrin (RBC)
moderately increased in Uroporphyrin (feces)
normal in Coproporphyrin
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HEMOGLOBINOPATHIES

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Hemoglobinopathies

Due to differences in the

arrangement of amino acids
in the polypeptide chain

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 Hemoglobinopathies
I. acc to molecular structure
A. Qualitative globin chain abnormalities

sequence in amino acid due to abnormal

substitution of amino acid in the chain.
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Major Groups of Hemoglobinopathies
Alpha-hemoglobinopathies: α globin chains
◦2nd most common group of hemoglobinopathies
Beta-hemoglobinopathies: β globin chains
◦Most common group of hemoglobinopathies
Gamma-hemoglobinopathies: γ globin chains
Delta-hemoglobinopathies: δ globin chains
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BETA-chain HEMOGLOBINOPATHIES

HbS α2β26GluVal Sickle cell anemia

HbC α2β26GluLys Hb C disease
HbE α2β226GluLys Hb E disease
HbD α2β2121GluLys Hb D disease

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 Dithionite Tube Test for Hemoglobin S
Principle:
◦ RBCs  lysed by saponin
◦ Sodium dithionite removes O2 from the test environment

Principle:
◦ Hb S polymerizes in the resulting deoxygenated state and forms a precipitate.
◦ The ppt. consists of tactoids (liquid crystals)
◦ Tactoids refract & deflect light  turbid solution

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Sodium metabisulfite test
Sodium metabisulfite: deoxygenates Hb
Under deoxygenated state, Hb S causes the formation of
sickle cells.

Procedure:
●1 drp. blood (slide) + sod.metabisulfite
● Cover w/ glass slip and seal w/
petroleum jelly
● Examine after one hour.
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Two crystals related to Hb C:
1.Hb SC crystals:
- “Washington monument” in appearance
- crystals protruding RBC membrane

2. Hb CC crystals:
- hexagonal, elongated crystals
- crystals formed within RBC membrane

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 Hemoglobinopathies
I. acc to molecular structure
A. Quantitative Globin chain abnormality

THALASSEMIA: imbalance/ depletion of globin chain

α-thalassemia & β-thalassemia

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THALASSEMIA: Alpha-thalassemia
Depletion of alpha gene

◦Single gene deletion – silent carrier state

◦Two-gene deletion – alpha thalassemia minor
◦Three-gene deletion – Hb H disease
◦Four-gene deletion – Hemoglobin Bart / hydrops fetalis

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 THALASSEMIA: Beta thalassemia
Depletion of alpha gene

Beta thalassemia major Very low HbA | severe clinical manifectation

Beta thalassemia intermedia Slightly high HbA | available beta gene
Beta thalassemia minor Markedly increase HbA
Beta thalassemia minima Silent carrier | normal HbA, HbA2 & HbF

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