THALASSEMIAClinical Features

and Genetic Classification

Presented by::

Avik basu MODERATOR:

DR. SANTOSH KUMAR MONDALASSOCIATE PROFESSOR, PATHOLOGY

EyesFace

Skin

SpleenLiver

Bones

Patient presents with… Fatigue

Loss of Appetite

Jaundice

Abdominal Pain and Enlargement

Clinician finds…

Chipmunk Facies

Facial Pallor

Icterus

Hepatosplenomegaly

Complications that may follow…

Bacterial Infections

Iron Overload

TYPES OF THALASSEMIA

Alpha Thalassemia

Beta Thalassemia

Genetic changes in Alpha Thalassemia…

Deletion Mutations

Non-deletion Mutations

Structure of alpha gene

Types of Deletion Mutation in Alpha

Thalassemiaα-4.2 kb Leftward Deletion

α-3.7 kb Rightward Deletion

Types of NON-Deletion Mutation in Alpha

Thalassemia Chain Termination Mutation

RNA Splicing Mutation

Mutations in Poly[A] Addition Signal

TYPES OF ALPHA THALASSEMIA

α -Thalassemias Genetic Representation

Silent Carrier -α/αα

α-Thalassemia Trait-1

--/αα

α-Thalassemia Trait-2 -α/-α

Hemoglobin H Disease(formation of β4 tetramer)

--/-α

Hydrops Fetalis(formation of Hb Barts i.e. ϒ4)

--/--

Genetic changes in Beta Thalassemia…

Deletion Mutations

Non-deletion Mutations

Structure of Beta gene

Types of NON-Deletion Mutation in BETA

Thalassemia Transcription Mutations

Mutations in RNA Processing

Mutations in RNA Translation

TYPES OF BETA THALASSEMIA

β -Thalassemias Genetic Representation

β-Thalassemia Major β+/β+, β+/β0, β0/β0

β-Thalassemia Intermedia Milder variants of β+/β+ and β+/β0

β-Thalassemia Minor β+/β, β0/β

Beta thalassemic hemoglobinopathies

∂β hybrid genes

Activation of cryptic splice sites

Hyperunstable β globins

OTHER FORMS OF THALASSEMIA

∂ Thalassemia

∂β Thalassemia