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Prenatal screening & testing for Thalassemia :white_flower: (:yellow…
Prenatal screening & testing for Thalassemia :white_flower:
Terms
Hemoglobinopathy
Def: Genetic abnormality affects the
amount
or
structure
of one or more of the globin chains in Hb
Include
Thalassemia syndrome
α-thalassemia
β-thalassemia
def: group of genetic blood disorders -> defects in Hb production
inherited
AR
→ 25% Normal, 50% Carrier & 25% Affected
Structure Hb variant (Abn. Hb)
HbS
HbE
HbC
Molecular biology
Decreasing synthesis
α thal
(gene
deletion
)
Types
Deletional
α-thal (
M/C
:star:)
Non-deletional
α-thal mutation (Constant spring)
No. of genes deleted
α-thal 1 (--/αα)
2 α-globin-gene-deletions
(α0-genotype) - common
The Southeast Asian deletion (- - SEA)
The Filipino deletion (- - FIL)
The Mediterranean deletion (- - MED)
α-thal 2 (-α/αα)
HbH (--/-α)
Hb Barts (--/--)
β thal
(
point
mutation)
:arrow_down: การสร้าง & โครงสร้างไม่แข็งแรง
Types
β+:
some
β globin production
β0:
absent
β globin production
:whale2:
HbE
codon 26th mutation
Severit
y by each types :grapes:
Instable
Hb
:whale2:
HbE
26th codon point mutation
Hb CS
mutation at terminal codon
Normal Hb
Composed of Tetrametric proteins
2 pairs of globin chains
α-like chain
non- α like chain (aka β-like)*
Prevalence
Worldwide Prevalence
α-thal traits
SEA 1-30%
β-thal trait
Eastern Mediterranean 2-18%
4.4/10000 live births
Thailand Prevalence
α thal
(α-thal 1 & α-thal 2) 20 - 30%
HbE
10 - 53%
β thal 3 - 9%
Hb Constant Spring (α-thal 2 like effect)
α-thal
found around 20 - 30% around country ;
HbE
30-50% at
อีสาน
Major Thalassemia PathoPSO
Prevention & Control of Thalassemia
:grapes:
:yellow_heart:
Screening test
:sunny: Red cell indices :grapes:
MCV (mean cell volume)
MCH (mean cell Hb)
:sunny: OF test (Osmotic fragility)
:heavy_plus_sign: in
α thal 1 trait 93-97%
Homozygous Hb E thalassemia ds 100%
β thal trait 96-100%
:sunny: IC strip test for
α-thalassemia
:grapes:
:sunny: DCIP (dichlorophenolindophenol precipitation test)
:heavy_plus_sign: in
Hb E
Hb H
Hb Bart’s
:sunny: HbE screen
Strategies
:grapes:
:green_heart:
Diagnostic test
Protein chemistry methods:
Hb typing
Isoelectric focusing (
IEF
)
:frowning_face:
CAN'T
precise quanitfy Hb variants
High performance liquid chromatography (
HPLC
)
:smiley:
CAN
accurately quantitates HbA2 & HbF and identify many Hb variant than electrophoresis
HbA2 lvl in HPLC :grapes:
Capillary electrophoresis (
CE
)
β thal trait : Hb A2 > 3.5%
Abn. Hb: HbE trait, Homozygoues HbE, HbCS trait, Homozygous HbCS
:smiley: can seperates HbA2 from HbE
Molecular (DNA-based methods)
β-thalassemia
Dot blot and reverse dot blot
RFLP (restriction fragment length polymorphism analysis)
DNA sequencing
α-thalassemia
find Deletional alpha thal
Gap
PCR
Multiplex ligation dependent amplification (MLPA)
NIPD (non-invasive prenatal dx) for Thalassemia?
:purple_heart:
Prenatal Dx (PND)
Sonographic markers for Bart’s hydrops fetalis :grapes:
:green_heart:
Definite Dx
CVS
- Chorionic villous sampling
Amniocentesis
PBS
:!:
Major manifestation
Hb Bart’s hydrops fetalis
Homozygous β-thalassemia
β-thalassemia/Hb E
:book:
Back 2 Basics
Carrier
that has
HIGH risk
for Severe Thalassemia that needs
screening
β-thalassemia carrier
α-thalassemia 1 carrier
Hb E carrier
Trait/Carrier VS Diseases
Traits
Asymp
Not pale
No hepatosplenomegaly
Abn gene can passes into child
Diseases
Pale (many to few)
Hepatosplenomegaly
Slow body development
Extramedullary erythropoiesis
Infection
Chronic leg ulcer
Gallbladder stone
:<3:
Specific tests
Hb typing
PCR for α-thal gene (α thal-1, α thal-2)