Alpha Thalassemia in Southeast Asia

Summary

The script discusses alpha thalassemia, a genetic disorder prevalent in Asia and the Mediterranean, associated with malaria protection. It covers its clinical significance, prevalence, molecular defects, and management strategies including genetic counseling and prenatal diagnosis, emphasizing its impact in Southeast Asia.

Takeaways

• 🌏 Alpha thalassemia is a common genetic disorder prevalent in Asia, the Middle East, and Mediterranean countries, with increasing clinical significance in North America, Australia, and Europe due to migrations.
• 🌡 It is associated with areas where malaria is or was endemic, suggesting a possible protective role of carriers against malaria, although the exact reason remains unknown.
• 📊 A recent study in Thailand aimed to estimate the burden of alpha thalassemia using a comprehensive prevalence database for Southeast Asia, highlighting the need for more information on the disease.
• 🧬 Alpha thalassemia is caused by deletions or mutations in the alpha globin genes, leading to decreased or absent production of alpha globin chains and an excess of other chains, which are nonfunctional and cause hemolysis.
• 🔬 The clinical severity of alpha thalassemia correlates with the degree of alpha globin chain deficiency, which is a consequence of molecular defects in the alpha globin gene.
• 🏥 Diagnosis of alpha thalassemia can be confirmed through laboratory tests and molecular techniques, including CBC, RBC indices, and hemoglobin electrophoresis.
• 🧬 Molecular analysis is crucial for specific diagnosis, identifying common mutations in the alpha globin gene, especially in Southeast Asia where certain nondeletional mutations can be more clinically significant.
• 🩺 Management of alpha thalassemia varies; silent carriers and those with alpha thalassemia trait may not need treatment, while hemoglobin H disease can range from mild to severe and may require regular transfusions.
• ⚠️ Hydrops fetalis, the most severe form of alpha thalassemia, is typically fatal, but prenatal diagnosis and interventions like intrauterine transfusions can improve outcomes.
• 👨‍👩‍👧‍👦 Genetic counseling and prenatal diagnosis are essential to prevent the perpetuation of the disease and to prepare for the potential health burdens associated with severe forms of the disorder.
• 🏛 Community education and involvement are vital for the prevention and management of the long-term complications of alpha thalassemia, emphasizing the importance of awareness and proper healthcare systems.

Q & A

What is alpha thalassemia?

Alpha thalassemia is a genetic blood disorder characterized by reduced or absent production of alpha globin chains, leading to an imbalance in hemoglobin synthesis and causing various clinical manifestations.

Why is alpha thalassemia more prevalent in certain regions like Asia and the Middle East?

Alpha thalassemia is more prevalent in regions such as Asia and the Middle East because these areas are in tropical and subtropical regions where malaria is or was endemic, and carriers of the alpha globin gene mutations are thought to offer some protection against malaria.

What are the clinical significances of alpha thalassemia in different countries?

While alpha thalassemia is highly prevalent in Asia, the Middle East, and Mediterranean countries, its clinical significance is also noted in North America, Australia, and Europe due to massive migrations from areas where the disorder is endemic.

What is the estimated percentage of the world population that carries at least one alpha thalassemia variant?

It is estimated that up to 5% of the world population carries at least one variant of alpha thalassemia, with some populations reporting gene frequencies close to 80%.

What are the severe forms of alpha thalassemia that are seen in Southeast Asia?

In Southeast Asia, more severe forms of alpha thalassemia are observed, which can include hemoglobin H disease and hydrops fetalis, the latter of which is often lethal or incompatible with life.

What is the significance of the alpha and beta globin genes in the context of alpha thalassemia?

The alpha and beta globin genes are crucial for hemoglobin production. In alpha thalassemia, there are deletions or mutations in the alpha globin genes, leading to decreased or absent production of alpha globin chains and an excess of other globin chains, causing various clinical issues.

How are the different forms of alpha thalassemia classified based on the number of functional alpha genes?

The forms of alpha thalassemia are classified based on the number of functional alpha genes: silent carrier status with three functional genes, alpha thalassemia 3 with two functional genes, hemoglobin H disease with one functional gene, and hemoglobin Barts hydrops fetalis with no functional genes.

What are the common mutations observed in alpha thalassemia in Southeast Asia?

Common mutations in alpha thalassemia in Southeast Asia include deletions affecting one or two alpha genes, such as the Southeast Asian deletion, and nondeletional mutations that can have a more significant clinical impact, especially those affecting the alpha 2 globin gene.

How is alpha thalassemia diagnosed without the benefit of newborn screening results?

Diagnosis of alpha thalassemia without newborn screening results relies on a combination of history and physical examination, evidence of anemia, and laboratory tests such as complete blood count (CBC), red blood cell indices, hemoglobin electrophoresis, and molecular techniques.

What are the management strategies for different forms of alpha thalassemia?

Management of alpha thalassemia varies based on the form: silent carriers and alpha thalassemia trait may not require treatment, while hemoglobin H disease may require intermittent or regular blood transfusions, and hydrops fetalis may necessitate intrauterine interventions or stem cell transplantation.

Why is genetic counseling important in the context of alpha thalassemia?

Genetic counseling is important to inform at-risk couples about the potential for having children with severe forms of alpha thalassemia, such as hydrops fetalis, and to discuss options for prevention and management of the disorder.

What is the role of community education in the prevention and management of alpha thalassemia?

Community education is essential to raise awareness about alpha thalassemia, its symptoms, and the importance of diagnosis and management. This helps to prevent the perpetuation of the disorder within communities and ensures individuals receive appropriate care.

Outlines

00:00

🌏 Global Prevalence and Clinical Significance of Alpha Thalassemia

This paragraph discusses the widespread occurrence of alpha thalassemia, particularly in Asia, the Middle East, and Mediterranean countries. It notes the condition's clinical significance in regions like North America, Australia, and Europe, drawing parallels with other genetic disorders such as sickle cell anemia and beta thalassemia. The speaker highlights the correlation between the prevalence of alpha thalassemia and areas where malaria is or was endemic, suggesting a possible protective role against malaria for carriers of the condition. The paragraph also emphasizes the need for increased awareness and research in Thailand and Southeast Asia due to the high prevalence and clinical impact of severe forms of alpha thalassemia in these regions.

05:02

🧬 Genetic Mutations and Clinical Manifestations of Alpha Thalassemia

The second paragraph delves into the genetic aspects of alpha thalassemia, explaining the different forms of the condition based on the number of functional alpha genes. It describes silent alpha thalassemia, alpha thalassemia 3, hemoglobin H disease, and hemoglobin Barts hydrops fetalis, detailing their clinical implications and the potential for severe anemia. The speaker also discusses the types of mutations, predominantly deletions, that can lead to alpha thalassemia, and the significance of nondeletional mutations, especially those affecting the alpha 2 globin gene, which can result in more severe clinical manifestations. The paragraph concludes with a focus on common mutations in Southeast Asia, including the nondeletion variant seen in hemoglobin constant spring, and its increasing prevalence due to migration.

10:02

🩺 Diagnosis and Management of Alpha Thalassemia

This paragraph outlines the diagnostic process for alpha thalassemia, emphasizing the importance of laboratory tests such as CBC and RBC indices to identify anemia and microcytosis. It also mentions the use of molecular techniques for a definitive diagnosis. The speaker discusses the management of different forms of alpha thalassemia, noting that silent carriers typically do not require treatment, while individuals with hemoglobin H disease may need regular transfusions and are at risk of iron overload. Hydrops fetalis, a severe form of the disease, is highlighted as incompatible with life, although intrauterine transfusions have been used in some cases to improve outcomes. The paragraph concludes with a call for better data collection and molecular diagnosis to aid in the management of alpha thalassemia.

15:04

👨‍👩‍👧‍👦 Genetic Counseling and Public Health Implications of Alpha Thalassemia

The final paragraph focuses on the importance of genetic counseling and prenatal diagnosis in preventing the transmission of severe forms of alpha thalassemia. It discusses the risk of having a child with hydrops fetalis and the potential for parents who are carriers to have children with varying degrees of the disease. The speaker emphasizes the role of community education and the need for physicians to be trained in the diagnosis and management of alpha thalassemia, as it can present similarly to other common anemias. The paragraph also touches on the long-term complications of anemia and iron overload, highlighting the need for multi-specialty care and public health strategies to address these issues effectively.

Keywords

💡Alpha Thalassemia

Alpha Thalassemia is a genetic blood disorder characterized by a reduced or absent production of alpha globin chains in hemoglobin. It is the main theme of the video, which discusses its prevalence, clinical significance, and impact on populations, particularly in Southeast Asia. The script mentions various forms of the disease, such as silent carrier status, Hemoglobin H disease, and Hydrops Fetalis, which are all related to the number of functional alpha genes.

💡Genetic Abnormalities

Genetic abnormalities refer to any alteration in the genome that leads to disease or health conditions. In the context of the video, alpha thalassemia is one such genetic abnormality that is highly prevalent in certain regions. The script outlines how this genetic condition affects the production of hemoglobin, impacting the health of carriers and individuals with the disease.

💡Hemoglobin

Hemoglobin is a protein in red blood cells that binds oxygen and transports it throughout the body. The video explains that in alpha thalassemia, there is a disruption in the production of hemoglobin due to a deficiency in alpha globin chains, which affects the oxygen-carrying capacity of red blood cells.

💡Endemic

Endemic refers to a disease or condition that is regularly found among particular people or in a certain area. The script mentions that alpha thalassemia is found in tropical and subtropical areas where malaria is or was endemic, suggesting a possible evolutionary advantage for carriers of the alpha thalassemia trait in such regions.

💡Mutation

A mutation is a change in the DNA sequence that can lead to variations in genes. The video discusses how alpha thalassemia is caused by mutations or deletions in the alpha globin genes, resulting in a spectrum of disorders with varying clinical severity.

💡Clinical Significance

Clinical significance refers to the relevance or importance of a disease or condition in a medical context. The script emphasizes that while alpha thalassemia is common in certain regions, its clinical significance varies, with some populations experiencing more severe forms of the disease.

💡Carrier

A carrier in genetics is an individual who has a gene for a particular disease but does not show symptoms. The video explains that many people are carriers of the alpha thalassemia variant without showing clinical symptoms, yet they can pass the gene to their offspring.

💡Molecular Techniques

Molecular techniques are methods used to analyze and manipulate biological molecules, such as DNA. The script mentions that molecular techniques are used for the diagnosis of alpha thalassemia, allowing for the identification of specific mutations and deletions in the alpha globin genes.

💡Hemoglobinopathies

Hemoglobinopathies are a group of genetic disorders that affect the structure or production of hemoglobin. The video places alpha thalassemia within the context of hemoglobinopathies, discussing its prevalence and impact alongside other conditions like sickle cell anemia.

💡Genetic Counseling

Genetic counseling is the process of providing individuals and families with information on the implications of genetic disorders. The script highlights the importance of genetic counseling for families at risk of having children with alpha thalassemia, to prevent severe outcomes like Hydrops Fetalis.

💡Community Education

Community education refers to efforts to inform and engage communities about health issues. The video underscores the importance of educating communities about alpha thalassemia to prevent the perpetuation of the disease and manage its long-term complications effectively.

Highlights

Alpha thalassemia is a common genetic disorder prevalent in Asia, the Middle East, and Mediterranean countries.

The disorder is also seen in North America, Australia, and Europe, though its clinical significance varies.

Alpha thalassemias are associated with regions where malaria is endemic, suggesting a protective role for carriers against malaria.

The exact reason for the protective effect against malaria in carriers is still unknown despite extensive research.

In Southeast Asia, alpha thalassemia manifests in severe forms and is a significant health burden.

Massive migrations have spread the problem of alpha thalassemia to countries like Europe and North America.

An estimated 5% of the world population carries at least one alpha thalassemia variant.

Southeast Asia reports more severe forms of alpha thalassemia due to higher gene frequencies.

A recent study in Thailand aimed to estimate the burden of alpha thalassemia using a comprehensive prevalence database.

The study revealed a spatial distribution of alpha thalassemia alleles in Southeast Asia.

Alpha thalassemia is caused by deletions or mutations of the alpha globin gene, leading to decreased or no production of alpha globin chains.

Nonfunctional hemoglobins like hemoglobin Barts and hemoglobin H are produced in excess, causing hemolysis.

Different forms of alpha thalassemia are determined by the number of functional alpha genes.

Clinical classification of alpha thalassemia depends on the loss of alpha globin genes and the type of mutation.

There are 128 known deletions for alpha thalassemia, with most being deletions and some more clinically significant due to their impact on alpha chain production.

Non-deletion mutations affecting the alpha 2 globin gene can lead to more severe manifestations of the disease.

Common mutations in Southeast Asia include the non-deletion variant seen in Chinese sister hemoglobin constant spring.

Diagnosis of alpha thalassemia can be missed without newborn screening and requires a combination of history, physical examination, and laboratory tests.

Molecular techniques are used for specific diagnosis of alpha thalassemia, identifying common mutations.

Management of alpha thalassemia includes proper workup for carriers, especially if anemia develops, and avoiding prophylactic iron.

Hemoglobin H disease can range from mild to severe and may require regular transfusions, leading to iron overload.

Hydrops fetalis, the most severe form of alpha thalassemia, is often fatal, but some cases have survived with intrauterine transfusions and are candidates for stem cell transplant.

Genetic counseling and prenatal diagnosis are crucial in preventing the disease and managing long-term complications.

Community education and physician training are essential for the prevention and management of alpha thalassemia.

The prognosis for alpha thalassemia varies, with good outcomes for asymptomatic carriers but variable outcomes for hemoglobin H disease due to potential iron accumulation.

Transcripts

alpha phalasinia is one of the most common uh

modelling genetic abnormalities

uh it is highly prevalent in the Asia

in the Middle East in the Mediterranean countries

however

seen in clinical significance in other countries

like the North America

Australia and Europe this is the outline of my top

no just like any other uh

globing gene disorders like your

or sickle cell anemia and your beta fallassemia

your alpha fallassemias

are found in the tropical and subtropical areas

where malaria was or is endemic

and it is thought that carriers of this immoglobin

authorities offer Protection against malaria

and the reason behind this is still unknown

despite extensive research

now as I've said before it is common in Asia

and specifically in Southeast Asia

where it's clinical significant is uh

uh seen in different forms of alpha celacemias

with severe manifestations however

because of massive migrations

this become a problem in other parts of the country

like Europe and North America

as of now it is estimated

that up to 5% of the world population cares

at least one alpha philassemia variant

with some populations reporting gene frequencies

close to 80% but it is more clinically significant in

Southeast Asia where you see

the more severe forms of alpha philassemia

now this is why in Thailand

uh

knowing uh there's uh

grooving

demand for more information regarding the prevalence

and

estimates of health burden for this disease

several studies were done in

this is one of the most recent published study

and this was done in Thailand

where it aim to estimate

the burden of alpha fellasinia in Thailand

using a comprehensive prevalence database

for Southeast Asia now this is uh

this map is a uh

reflection of the spatial distribution

of the prevalence in the sample sizes

no of your alpha alacemia alleles in the range or no

as as a result of this study

and this comprised countries like a Moja

allows in Vietnam and of course Thailand

in the because of this

the result of the study estimated around 3,000 95

who borns

and this paper also highlights the need

2 alpha globingine in your chromosome 16

and 1 beta globingine in your

and the last senior refers to a spectrum of disorders

characterized by reduced or absent

production of one or more non alpha

in alpha global chains and

this results in the disruption of the delicate balance

oh as I've said before

alpha phalascemia is due to deletions

or mutation of your alpha globingine

and what happens is that there will be decreased

or option production of your

alpha

globin chain and as a result

there will be excess production of

your gamoglobin chains in the Newborn

in these forms your hemoglobin Barts

and after the Newborn period will be excess uh

meta globin chain production in this

to your hemoglobin each

now this uh uh hemoglobins are nonfunctional

they cannot deliver oxygen effectively

and they stick to RBC membranes causing hemolysis

now

slide is a glowing chain plaster now depending

functional alpha genes you will have

the different forms of your alpha thalassemia

so and you have a silent alpha thalassemia

when when there is three functional gene in

if only two functional genes

you will have your alpha salascemia 3

which can be homozygous or heterozygous

and if only one functional gene

alpha gene

then you will have your hemoglobin H disease

and of course if no functional gene

then this will give rise to your hemoglobin uh

Barts hydropsythalese

which is lethal or not compatible with life

now this is

the clinical classification of alpha thalassemia

or the genotype phenotype correlation

and this depends on the neck loss of alphaglobin gene

which can be due to the number of alphaglobin

gene affected

which alpha globe in low side is affected

whether it's a deletional

or nondeletional form of mutation

or if it's a non deletional then there's no mutation

partially or fully anemia at all

while with those with alacemia

treat will have MALD anemia and microsatosis

and examination of your peripheral smear

while your hemoglobin H

disease can vary from moderate to severe anemia

having mild jaundice and moderate hepatosplanomegaly

and of course

your hydropspitalis is not compatible with life

fetuses born will have severe anemia

journalists and edemaciitis Mark hepatospline omegaly

skeletal and cardiovascular malformations uh

will be noted

now

these are the different types of mutations in alpha

palasinia

most of these mutations are uh are are deletions

no in fact

today there are already 128 known deletions

uh for alpha phalasinia and uh molecular defects

no and most of these are uh deletions

it can have small deletions

where in 1 alpha gene is just uh

affected and uh several recombinations are produced

and these are the common mutations and uh uh that are

are observed not uh listed in this line

there can be large deletions involving two alpha genes

in the most common of this is your Southeast Asia

deletions

however it is the non deletions that are considered uh

sometimes more clinically significant

no uh in fact this deletions

this non deletions

give rise to more severe reduction of your alpha chain

cymme disease and this phenomenon may be explained

but by the fact

majority of these mutations affect your hemoglobin

E2 gene this alpha 2

globin gene is considered the dominant adult

moglobin gene which is expressed at two to three fold

higher levels than your alpha 1 globin gene

at most mrna and protein levels

so that when it is affected

the transcription of this

effective alpha 2 globin gene

also interferes with your alpha 1

further reducing alpha globin chain production

more Malica say if your alpha 1 is affected

there is a compensation

or compensatory reaction of your alpha 2 globin gene

however when your alpha 2 globin gene is affected

it creates a more severe uh

reduction in your alpha globe in gene production

hence in more clinically significant manifestation

now these

are the common mutations

in alpha thalassema in Southeast Asia

and uh one of the most common

non deletion variants in Southeast Asia

among Chinese sister hemoglobin constant spring

uh this hemoglobin constant spring is uh seen in

has a gene frequency of 8%

and this results from a mutation

a termination cordon of your alpha tube globin gene

which leads to synthesis

the synthesis of unstable and elongated alpha globin

ah chin additionally

they have more AH30 one amino acids more

and this is the most prevalent nondeletional ah

alpha thalassemia in in in the region

specifically in China and Southeast Asia

and it is gained increase incidents

nor there's increasing incidents

in other parts of the world

as I've said before because of migration

and it creates a more

a moderately severe form of alpha fallassemia uh

with a binding of your uh

alpha constant spring

globin chain on the inner membrane of your red blood

cell containing your hemoglobin constant spring

and this can cost are increasing molyses

and unusual pathombiology of red blood cells

among patients are having this mutation

now it can be missed not in uh HPLC

but can be detected uh

more efficiently in your capillary electrophoresis

now how do we diagnose alpha phylescemia

without the benefit of the results of Newborn screening

well uh history and physical examination uh

evidence of anemia can lead us to diagnosis

but we need laboratory exams to uh uh

make the diagnosis of

complete diagnosis of alpha thalassemia

and with your CBC and rbc in

this is uh uh

you can see uh degree of high hypochromia

microsatosis in anemia

based on the results of your CBC and RBC in disease

and you will see in this slide that

the level of your hemoglobin correlates well

with the

number of your functional genes

no as you can see in the first graph

if you have a normal uh genotype

no mutations then you have a normal individual

without any evidence of hemolysis or anemia

without abnormality in your uh

uh level of your

uh mean cell volume or your MCV or your mean cell uh

monogloping concentrations manifested in your uh

RBC indecessors no

so but normal no

no genetic

no gene abnormalities nor volume levels but as

as the number of functional genes decreases

you will see that the values of your ammogular

being your MCV m m m C H also decreases

this can also be evident

upon examination of your peripheral smear

where you will see hypochromia

microcytosis target cell formation

uh you can see occasional sphere sites and upon uh

staining of your smear with your brilliant crusty blue

you will see inclusion bodies

now uh your hemoglobin A2 levels

no by using HPLC and capillary electroforesis can

you can also see no further decrease

no in your hemoglobin A2 level

and this correlates well

with the number of functional genes uh

uh involved and uh

this is an example of an adult uh

hemoglobin electrophoresis

your hblc and capillary electrophoresis demonstrating

demonstrating the presence of your hemoglobin H

now

you can specifically diagnose alpha thalassemia using

uh molecular techniques

and these are the common uh uh diagnostic uh way

uh in in molecular biomolecular analysis K

now let's go to alpha thalassemia management

hopefully in the near future

we'll have a complete no data in our registry

the types of alpha thalassemia we have

as well as using this molecular

way of diagnosing alpha thalassemia

the common mutations that will lead or are are um

observed in our country

how do we manage palasemia for alpha salassemia

treat no need for treatment because they are

they have no anemia or they might have anemia

which can be very mild

and the carriers of this alpha salassemia treat however

should be properly worked up

no uh especially if they develop anemia

because

there may be coexisting nutritional deficiencies

and once diagnosed to have uh

nutritional deficiency anemias

then they should be treated accordingly

however prophylactic iron should not

never be given to carriers

no alpha alacemia

especially those who are at risk of developing

iron overload

how about immoglobin H disease

it can be a mild to severe disorder

and it depends on the mutation

which influences the clinical severity

the delusional type has milder disease

with intermittent transfusion

however

the non delusional type has moderately to severe

anemia which been omegaly

it might require regular transfusions early in infancy

up to late adulthood and because of this uh

regular transmission they can have iron overload

now for Hydrox fatales uh

this is not compatible with life

but in in some uh institutions

intrauterine transfusions

following early detection

have resulted in the birth of this nonhydropic uh

infants and this infants uh survive

will survive because of this intervention

are good candidates for him

at the poetic stem cell transplant transplantation

now genetic counseling and untenatal diagnosis

is available in most part of uh

South East Asia and this is important to prevent uh

perpetration of the disease as well as uh

having a child with a hydroxphatales

now for example

if you have a father who has mild anemia is considered

uh the portal acemia trait

having uh two genes missing

and a mother with no signs and symptoms of anemia

but uh they uh become parents

no or there is always a chance of having a child

no of uh having a hemoglovine age disease

uh for every birth or for every pregnancy

a 25% chance of having a child with multiple H disease

now there will be children without anemia

no normal no genes missing

there can be uh

children with silent carrier or uh with alacemia three

however if one of the carrier is a homozygal

then the risk of having a hemoglobin

age disease increases to 50%

for every pregnancy and when both parents

carry an alpha salascemia mutation

then this type of mutation

the risk of their offspring having hemoglobin Barts

hydrospitalis is 25% so important italegrate

if you know the type of alpha celestinia

you have type of mutation

so that parents can be advised

regarding the pregnancy of the mother

now it's also important that

position in the community

are involved in the management of Palestinians

individuals of one

with one of the various forms of polycemia trait

may be entirely as symptomatic

unaware of their diagnosis

and procreate with other individuals with the same

trait

thereby perpetuating the disorder within the community

so important in a uh physicians know this

and that

they are trained in the diagnosis and management of

alpha phalasemia

since it has similar presentation with other

common diseases causing anemia

like nutritional anemis and chronic blood loss

so Nissan Phosayne anemis know uh

everybody stated as iron deficiency

where us in Pala we have telesemia

and of course physicians should know

how to address the long term complications of anemia

in iron overload

and this requires multi specialty care

under well formulated guidance

prognosis is good generally

for those who are asymptomatic and with bad anemia

but the outcome for hemoglobin H disease is variable

especially the long term problem of iron accumulation

which can be a more severe problem

for nondeletional type of alpha cell acemia

and of course in general not

this may depend on the awareness

and availability of healthcare systems

equipped to address the law

this long term complications of the disease as well

it's public health uh implication

in summary I have presented alpha thalassemia

this presentation

patho physology as well as diagnosis and management

and this are this my take home message

alfasal acemia

so why you distributed all over the world

it is a clinically significant health

uh problem in Southeast Asia

or severe variants of the disease exist

and there are four major phenotypes

the silent carrier dalpathel acemia

3HBH disease and hydrosphetolysis Vitalis

and the clinical severity correlates well

with a degree of alpha globin chain deficiency

which is a consequence of molecular

defects in the alpha globin gene

diagnosis is confirmed by both laboratory

and molecular techniques and the genetic and antinatal

uh genetic and antinatal counseling are important

to avoid pregnancies with mogulbin parts

with Ali syndrome which causes munatal death

positions and decision

and community education are essential

in the prevention

in management long term complications

thank you very much

Ang alpha phalasinia ay isa sa pinakakaraniwang uh

Pagmomodelo ng mga genetic abnormalities

uh ito ay lubos na laganap sa Asya

sa Gitnang Silangan sa mga bansang Mediteraneo

gayunpaman

nakikita sa klinikal na kahalagahan sa ibang mga bansa

tulad ng North America

Australia at Europe ito ang balangkas ng aking tuktok

hindi tulad ng iba uh

globing gene disorder tulad ng sa iyo

o sickle cell anemia at ang iyong beta fallassemia

iyong alpha fallassemias

ay matatagpuan sa mga tropikal at subtropikal na lugar

kung saan ang malaria ay o endemic

at ito ay naisip na carrier ng immoglobin na ito

Nag-aalok ang mga awtoridad ng Proteksyon laban sa malaria

at ang dahilan sa likod nito ay hindi pa rin alam

sa kabila ng malawak na pananaliksik

ngayon gaya ng sinabi ko noon ay karaniwan na sa Asya

at partikular sa Timog Silangang Asya

kung saan ito ay klinikal na makabuluhan ay uh

uh nakikita sa iba 't ibang anyo ng alpha celacemias

na may malubhang manifestations gayunpaman

dahil sa napakalaking migrasyon

nagiging problema ito sa ibang bahagi ng bansa

tulad ng Europa at Hilagang Amerika

sa ngayon ay tinatantya

na hanggang 5% ng populasyon ng mundo ay nagmamalasakit

kahit isang variant ng alpha philassemia

na may ilang populasyon na nag-uulat ng mga frequency ng gene

malapit sa 80% ngunit ito ay mas klinikal na makabuluhan sa

Southeast Asia kung saan mo nakikita

ang mas malubhang anyo ng alpha philassemia

ngayon ito ang dahilan kung bakit sa Thailand

eh

knowing uh meron uh

pag-ukit

demand para sa karagdagang impormasyon tungkol sa pagkalat

at

Mga pagtatantya ng pasanin sa kalusugan para sa sakit na ito

ilang pag-aaral ang ginawa sa

ito ay isa sa pinakahuling nai-publish na pag-aaral

at ito ay ginawa sa Thailand

kung saan nilalayon nitong tantiyahin

ang pasanin ng alpha fellasinia sa Thailand

gamit ang isang komprehensibong database ng prevalence

para sa Southeast Asia ngayon ito ay uh

ang mapa na ito ay isang uh

salamin ng spatial distribution

ng pagkalat sa mga laki ng sample

wala sa iyong alpha alacemia alleles sa hanay o hindi

bilang resulta ng pag-aaral na ito

at ito ay binubuo ng mga bansa tulad ng isang Moja

pinapayagan sa Vietnam at siyempre Thailand

sa dahil dito

ang resulta ng pag-aaral ay tinatayang nasa 3,000 95

sino ang ipinanganak

at itinatampok din ng papel na ito ang pangangailangan

2 alpha globingine sa iyong chromosome 16

at 1 beta globingine sa iyong

at ang huling senior ay tumutukoy sa isang spectrum ng mga karamdaman

nailalarawan sa pamamagitan ng nabawasan o wala

produksyon ng isa o higit pang hindi alpha

sa alpha global chain at

Nagreresulta ito sa pagkagambala ng maselang balanse

oh gaya ng sinabi ko kanina

Ang alpha phalascemia ay dahil sa mga pagtanggal

o mutation ng iyong alpha globingine

at ang mangyayari ay mababawasan

o opsyon na produksyon ng iyong

globin chain at bilang isang resulta

magkakaroon ng labis na produksyon ng

Your Gamoglobin chain sa Bagong panganak

sa mga form na ito ang iyong hemoglobin Barts

at pagkatapos ng Newborn period ay magiging labis uh

meta globin chain production dito

sa iyong hemoglobin bawat isa

ngayon itong uh uh hemoglobins ay nonfunctional

hindi sila makapaghatid ng oxygen nang epektibo

at dumidikit sila sa mga lamad ng RBC na nagdudulot ng hemolysis

ngayon

Ang slide ay isang kumikinang na chain plaster ngayon depende

functional alpha genes na magkakaroon ka

ang iba 't ibang anyo ng iyong alpha thalassemia

So at mayroon kang tahimik na alpha thalassemia

kapag may tatlong functional gene sa

kung dalawang functional genes lang

magkakaroon ka ng iyong alpha salascemia 3

na maaaring homozygous o heterozygous

at kung isang functional gene lang

gene ng alpha

pagkatapos ay magkakaroon ka ng iyong hemoglobin H disease

at siyempre kung walang functional gene

tapos ito ang magbubunga ng hemoglobin mo uh

Ang hydropsythalese ni Barts

na nakamamatay o hindi tugma sa buhay

ngayon ito ay

ang klinikal na pag-uuri ng alpha thalassemia

o ang genotype phenotype correlation

at ito ay depende sa pagkawala ng leeg ng alphaglobin gene

na maaaring dahil sa bilang ng alphaglobin

apektado ang gene

aling alpha globe sa mababang bahagi ang apektado

kung ito ay isang pagtanggal

o nondeletional na anyo ng mutation

o kung ito ay isang hindi pagtanggal, walang mutation

Bahagyang o ganap na anemia sa lahat

habang kasama ang mga may alacemia

Magkakaroon ng MALD anemia at microsatosis ang treat

at pagsusuri ng iyong peripheral smear

habang ang iyong hemoglobin H

Ang sakit ay maaaring mag-iba mula sa katamtaman hanggang sa malubhang anemia

pagkakaroon ng banayad na paninilaw ng balat at katamtamang pagplano ng hepatos

at syempre

ang iyong hydropspitalis ay hindi tugma sa buhay

Ang mga fetus na ipinanganak ay magkakaroon ng matinding anemia

mga mamamahayag at edemaciitis Mark hepatospline omegaly

skeletal at cardiovascular malformations uh

mapapansin

ngayon

ito ang iba 't ibang uri ng mutasyon sa alpha

Palatin

karamihan sa mga mutasyon na ito ay uh ay mga pagtanggal

hindi talaga

ngayon ay mayroon nang 128 na kilalang pagtanggal

uh para sa alpha phalasinia at uh molecular defects

hindi at karamihan sa mga ito ay uh mga pagtanggal

maaari itong magkaroon ng maliliit na pagtanggal

saan sa 1 alpha gene ay uh lang

apektado at uh ilang recombinations ang ginawa

at ito ang mga karaniwang mutasyon at uh uh iyon

ay sinusunod hindi uh nakalista sa linyang ito

maaaring magkaroon ng malalaking pagtanggal na kinasasangkutan ng dalawang alpha genes

sa pinakakaraniwan dito ay ang iyong Southeast Asia

Mga pagtanggal

gayunpaman, ang mga hindi pagtanggal ang itinuturing na uh

minsan mas klinikal na makabuluhan

hindi uh sa katunayan ang mga pagtanggal na ito

itong hindi pagtanggal

magbunga ng mas matinding pagbabawas ng iyong alpha chain

cymme disease at ang hindi pangkaraniwang bagay na ito ay maaaring ipaliwanag

ngunit sa katotohanan

Karamihan sa mga mutasyon na ito ay nakakaapekto sa iyong hemoglobin

E2 gene itong alpha 2

Ang globin gene ay itinuturing na nangingibabaw na nasa hustong gulang

Moglobin gene na ipinahayag sa dalawa hanggang tatlong beses

mas mataas na antas kaysa sa iyong alpha 1 globin gene

At karamihan sa mga antas ng mrna at protina

para kapag naapektuhan

ang transkripsyon nito

epektibong alpha 2 globin gene

nakakasagabal din sa iyong alpha 1

higit pang pagbabawas ng produksyon ng alpha globin chain

More Malica say kung apektado ang alpha 1 mo

may kabayaran

o compensatory reaction ng iyong alpha 2 globin gene

gayunpaman kapag ang iyong alpha 2 globin gene ay apektado

Lumilikha ito ng mas malala uh

pagbawas sa iyong alpha globe sa paggawa ng gene

samakatuwid sa mas klinikal na makabuluhang pagpapakita

ngayon ang mga ito

ay ang mga karaniwang mutasyon

sa alpha thalassema sa Timog Silangang Asya

at uh isa sa pinakakaraniwan

mga variant ng hindi pagtanggal sa Southeast Asia

sa mga Chinese kapatid na babae hemoglobin pare-pareho spring

uh itong hemoglobin constant spring ay makikita sa

ay may dalas ng gene na 8%

at ito ay nagreresulta mula sa isang mutation

isang termination cordon ng iyong alpha tube globin gene

na humahantong sa synthesis

ang synthesis ng hindi matatag at pinahabang alpha globin

ah baba din

mas marami silang AH30 isang amino acids pa

at ito ang pinakalaganap na nondeletional ah

alpha thalassemia sa in sa rehiyon

partikular sa Tsina at Timog Silangang Asya

at ito ay nakakuha ng pagtaas ng mga insidente

o dumarami ang mga insidente

sa ibang bahagi ng mundo

gaya ng sinabi ko noon dahil sa migration

at lumilikha ito ng higit pa

isang katamtamang malubhang anyo ng alpha fallassemia uh

na may pagkakatali ng iyong uh

alpha pare-pareho ang tagsibol

globin chain sa panloob na lamad ng iyong pulang dugo

cell na naglalaman ng iyong hemoglobin constant spring

at ito ay maaaring gastos ay pagtaas ng molyses

at hindi pangkaraniwang pathombiology ng mga pulang selula ng dugo

sa mga pasyente ay nagkakaroon ng mutation na ito

ngayon maaari itong makaligtaan hindi sa uh HPLC

pero pwedeng ma-detect uh

mas mahusay sa iyong capillary electrophoresis

ngayon paano natin masuri ang alpha phylescemia

nang walang pakinabang ng mga resulta ng Newborn screening

Well uh kasaysayan at pisikal na pagsusuri uh

Ang katibayan ng anemia ay maaaring humantong sa amin sa diagnosis

pero kailangan namin ng laboratory exams para uh uh

gawin ang diagnosis ng

kumpletong diagnosis ng alpha thalassemia

at kasama ang iyong CBC at rbc

ito ay uh uh

makikita mo ang uh degree ng mataas na hypochromia

Microsatosis sa anemia

batay sa mga resulta ng iyong CBC at RBC sa sakit

at makikita mo sa slide na ito na

ang antas ng iyong hemoglobin ay mahusay na nakakaugnay

kasama ang

bilang ng iyong mga functional na gene

hindi tulad ng makikita mo sa unang graph

kung mayroon kang isang normal na uh genotype

walang mutations tapos may normal kang indibidwal

nang walang anumang katibayan ng hemolysis o anemia

walang abnormalidad sa uh mo

uh level mo

uh mean cell volume o ang MCV mo o ang mean cell mo uh

Ang mga monogloping na konsentrasyon ay ipinakita sa iyong uh

Mga index ng RBC no

So pero normal no

walang genetic

walang mga abnormalidad sa gene o mga antas ng volume ngunit bilang

habang bumababa ang bilang ng mga functional genes

makikita mo na ang mga halaga ng iyong ammogular

Ang pagiging MCV mo m m C H ay nababawasan din

ito ay maaari ding maging maliwanag

sa pagsusuri ng iyong peripheral smear

kung saan makikita mo ang hypochromia

Microcytosis target na pagbuo ng cell

uh makikita mo ang paminsan-minsang mga sphere site at sa uh

paglamlam ng iyong pahid ng iyong makinang na magaspang na asul

makikita mo ang inclusion bodies

ngayon uh ang iyong mga antas ng hemoglobin A2

hindi sa pamamagitan ng paggamit ng HPLC at capillary electroforesis maaari

wala ka ring makikitang pagbaba

wala sa iyong hemoglobin A2 level

at ito ay may kaugnayan nang maayos

sa dami ng functional genes uh

uh kasali at uh

ito ay isang halimbawa ng isang matanda uh

electrophoresis ng hemoglobin

iyong hblc at capillary electrophoresis na nagpapakita

Pagpapakita ng presensya ng iyong hemoglobin H

ngayon

maaari mong partikular na masuri ang alpha thalassemia gamit

uh mga pamamaraan ng molekular

at ito ang karaniwang uh uh diagnostic uh na paraan

uh sa molecular biomolecular analysis K

ngayon pumunta tayo sa alpha thalassemia management

sana sa malapit na hinaharap

magkakaroon kami ng kumpletong walang data sa aming registry

ang mga uri ng alpha thalassemia na mayroon tayo

pati na rin ang paggamit ng molekular na ito

paraan ng pag-diagnose ng alpha thalassemia

ang mga karaniwang mutasyon na hahantong o ay um

naobserbahan sa ating bansa

Paano natin pinamamahalaan ang palasemia para sa alpha salassemia

hindi na kailangan ng paggamot dahil sila ay

wala silang anemia o baka may anemia sila

na maaaring maging napaka banayad

at ang mga carrier ng alpha salassemia na ito ay gumagamot gayunpaman

dapat maayos na magtrabaho

No uh lalo na kung nagkakaroon sila ng anemia

kasi

Maaaring may magkakasamang kakulangan sa nutrisyon

at minsang na-diagnose na may uh

Mga anemia sa kakulangan sa nutrisyon

pagkatapos ay dapat silang tratuhin nang naaayon

gayunpaman ang prophylactic iron ay hindi dapat

hindi kailanman ibibigay sa mga carrier

walang alpha alacemia

lalo na ang mga nasa panganib na umunlad

sobrang karga ng bakal

paano ang sakit na immoglobin H

maaari itong maging banayad hanggang malubhang karamdaman

at depende ito sa mutation

nakakaimpluwensya sa klinikal na kalubhaan

ang uri ng delusional ay may mas banayad na sakit

na may pasulput-sulpot na pagsasalin ng dugo

gayunpaman

ang hindi delusional na uri ay may katamtaman hanggang malubha

Anemia na naging omegaly

Maaaring mangailangan ito ng mga regular na pagsasalin sa maagang pagkabata

hanggang late adulthood at dahil dito uh

Regular transmission maaari silang magkaroon ng iron overload

ngayon para sa Hydrox fatales uh

hindi ito tugma sa buhay

ngunit sa ilang uh institusyon

Mga pagsasalin ng intrauterine

kasunod ng maagang pagtuklas

Nagresulta sa pagsilang nitong nonhydropic uh

mga sanggol at ang mga sanggol na ito uh ay nabubuhay

mabubuhay dahil sa interbensyong ito

ay mabubuting kandidato para sa kanya

At ang patula stem cell transplant transplantation

ngayon ay genetic counseling at untenatal diagnosis

ay magagamit sa karamihan ng bahagi ng uh

Timog Silangang Asya at ito ay mahalaga upang maiwasan uh

Perpetration ng sakit pati na rin uh

pagkakaroon ng anak na may hydroxphatales

ngayon halimbawa

kung mayroon kang isang ama na may banayad na anemia ay isinasaalang-alang

uh ang katangian ng portal acemia

pagkakaroon ng uh dalawang gene na nawawala

at isang ina na walang palatandaan at sintomas ng anemia

pero uh naging magulang na sila

wala o laging may pagkakataon na magkaroon ng anak

No of uh pagkakaroon ng hemoglovine age disease

uh para sa bawat kapanganakan o para sa bawat pagbubuntis

isang 25% na posibilidad na magkaroon ng anak na may multiple H disease

ngayon ay magkakaroon ng mga batang walang anemia

No normal walang genes na nawawala

pwede naman eh

mga batang may silent carrier o uh na may alacemia tatlo

gayunpaman kung ang isa sa carrier ay isang homozygal

pagkatapos ay ang panganib ng pagkakaroon ng hemoglobin

Ang sakit sa edad ay tumataas sa 50%

para sa bawat pagbubuntis at kapag ang parehong mga magulang

magdala ng alpha salascemia mutation

pagkatapos ang ganitong uri ng mutation

ang panganib ng kanilang mga supling na magkaroon ng hemoglobin Barts

Hydrospitalis ay 25% kaya mahalagang italegrate

kung alam mo ang uri ng alpha celestinia

mayroon kang uri ng mutation

para mapayuhan ang mga magulang

tungkol sa pagbubuntis ng ina

ngayon mahalaga din yan

posisyon sa komunidad

ay kasangkot sa pamamahala ng mga Palestinian

mga indibidwal ng isa

na may isa sa iba 't ibang anyo ng katangian ng polycemia

Maaaring ganap na kasing sintomas

hindi alam ang kanilang diagnosis

at magkaanak sa ibang mga indibidwal na may pareho

katangian

sa gayon ay nagpapatuloy ang kaguluhan sa loob ng komunidad

Napakahalaga sa isang uh na alam ito ng mga manggagamot

at iyon

sila ay sinanay sa pagsusuri at pamamahala ng

dahil ito ay may katulad na pagtatanghal sa iba

Mga karaniwang sakit na nagdudulot ng anemia

tulad ng nutritional anemis at talamak na pagkawala ng dugo

So alam ng Nissan Phosayne anemis uh

sinabi ng lahat bilang kakulangan sa bakal

Where us in Pala meron tayong telesemia

at siyempre dapat malaman ng mga manggagamot

kung paano tugunan ang mga pangmatagalang komplikasyon ng anemia

sa sobrang karga ng bakal

at nangangailangan ito ng multi specialty na pangangalaga

Under well formulated guidance

Ang pagbabala ay mabuti sa pangkalahatan

Para sa mga asymptomatic at may masamang anemia

ngunit ang kinalabasan para sa hemoglobin H disease ay variable

lalo na ang pangmatagalang problema ng akumulasyon ng bakal

na maaaring maging isang mas matinding problema

para sa nondeletional na uri ng alpha cell acemia

at siyempre sa pangkalahatan ay hindi

ito ay maaaring depende sa kamalayan

at pagkakaroon ng mga sistema ng pangangalagang pangkalusugan

nilagyan upang tugunan ang batas

ito pangmatagalang komplikasyon ng sakit pati na rin

ito ay pampublikong kalusugan uh implikasyon

sa buod ay ipinakita ko ang alpha thalassemia

ang pagtatanghal na ito

Patolohiya ng patho pati na rin ang diagnosis at pamamahala

at ito ang aking mensahe sa pag-uwi

alphasal acemia

kaya bakit mo ipinamahagi sa buong mundo

ito ay isang klinikal na makabuluhang kalusugan

uh problema sa Southeast Asia

o umiiral ang mga malubhang variant ng sakit

at mayroong apat na pangunahing phenotypes

ang tahimik na carrier dalpathel acemia

3HBH sakit at hydrosphetolysis Vitalis

at ang klinikal na kalubhaan ay mahusay na nauugnay

na may antas ng kakulangan sa alpha globin chain

na bunga ng molekular

mga depekto sa alpha globin gene

Ang diagnosis ay kinumpirma ng parehong laboratoryo

at mga molecular technique at ang genetic at antinatal

uh mahalaga ang genetic at antinatal counseling

upang maiwasan ang pagbubuntis na may mga bahagi ng mogulbin

With Ali syndrome na nagiging sanhi ng unang kamatayan

mga posisyon at desisyon

at ang edukasyon sa komunidad ay mahalaga

sa pag-iwas

sa pamamahala ng pangmatagalang komplikasyon

maraming salamat