epid hb malaysia

8/3/2019 Epid Hb Malaysia

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Epidemiology of

Haemoglobinopathies in Malaysia

15th September 2011


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Multiracial


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Multiracial population

Indigenous

West Malaysia

Proto-Malay, Negrito, Senoi

East Malaysia

Sabah Kadazandusun, Bajau, Murut

Sarawak Dayaks, Iban, Bidayuh, Orang

Ulu

Malays

Chinese

Indians

Tamils

Gujeratis

Punjabis

Pakistanis Ceylonese


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Malaysia:Population 28.2 million

Statistics 2010


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Ethnic groups

Statistics 2010

Indians

7.3%

Chinese

24.6%

Bumiputera

64.7%

Others0.7%

MalaysianCitizens

91.8%

Non-citizens

8.2%


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Origins


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Indigenous people

50 000 years ago- Paleolithic (early stoneage)

Out of Africa theory Orang asli


8/55Proto-Malays (Melayu Asli)


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Mekong river migration


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Cham- Malay


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Cham- Malay language

Malay Cham English Malay Cham English

Sungai Sungai River Lada Lada Pepper

Banyak Banyak More Gunung Gunung Mountain

Bintang Bintang Star Tembaga Tembaga Bronze

Manis Manis Sweet Timah Tima Tin

Anjing Anjing Dog Pahit Pahit Bitter

Sedikit Sedikit Less Mata Mata EyeIkan Ikan Fish Sini Ni Here

Orang Orang People Ayer Aya Water

Buat Buat Do Bapa Pak Father


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Malaysian-Chinese

15th century: Puteri Hang Li Po married Sultan Mansur Shahof Malacca

18th 19th century: Hokkien from Fujian district > Penang and Malacca > rubber

plantation

Teochew from Chaoshan district > JB, Selangor > pepper plantation

Hainanese from Hainan > Kemaman, Pulau Ketam > cooks

Hakka from Guangdong and Fujian > Perak, Selangor > miners

Cantonese from Guangdong and Guangxi > KL, Ipoh, Seremban,Sandakan > miners/ developers


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Malaysian-Indians

Early 20th century

Brought in by the British as labourers

Tamils- plantation Sri Lankan Tamils and Malayees: clerical

Punjabis- police force

Gujeratis and Sindhis: textile business 80% of total Indian community are Tamils

(South Indians)


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Malaysian-Indians


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Prevalence


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Worldwide

Approx. 270 million people (4.5% of worldpopulation) carry abnormal Hb genes

400 million people in South East Asia (SEA) 50% of carriers are in SEA


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South East Asia


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Prevalence in Malaysia

Cross-sectional study in Tanjong Karang

n= 111 screened

1 in 4 (25%) are carriers

*About 4.5% are carriers for thalassaemia

4.5% of Malaysian-Chinese are carriers for 0thalassaemia

Ainoon O, Malaysian J Pathol 1994

Thalassemia Carrier Diagnosis in Malaysia, E. George, Ed.,

pp. 16, SP-Muda Printing Sdn Bhd, Kuala Lumpur, Malaysia, 1998


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Pilot screening project, Form 4

Kota Belud,Sabah

Jasin, Melaka Timur Laut, PPinang

No. secondary

schools

8 18 37

No. pupils 1 592 3 062 7 281

No. screened 1 242 (78%) 2 905 (94.9%) 4 273 (58.7%)

trait 92 (7.4%) 48 (1.65%) 87 (2.0%)

HbE trait 10 (0.8%) 99 (3.4%) 86 (2.05)

trait 108 (8.3%) 44 (0.03%) 223 (5.2%)

Safiah B, MOH 2005-2006


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thalassaemias


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thalassaemias

Present throughout SEA

Higher in northern parts

30% in Chiengmai Province of Thailand vs. 0.5% inIndonesia

thal-2 is equally distributed

thal-1 is most frequent in Chiengmai (12.2%)

Fuchaeron S, Hemoglobin 1997


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thal-1

Deletion of both duplicated globin genes

17.5- 20kb deleted

gene is not deleted

Known as SEA 0 molecular defect (- - SEA)



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thal-2

2 types

Deletion of 4.2 kb DNA (leftward type, -4.2)

Deletion of 3.7 kb DNA (rightward type, -3.7)

-3.7 most common in Malaysia

-4.2 only found in Malaysian-Chinese

high frequencies of -4.2 in South China Guangxi 58%, Jiangxi 29%

E. George, Thalassemia Carrier Diagnosis in Malaysia, 1998


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Hb Constant Spring

1st isolated in a Chinese family from ConstantSpring district of Jamaica in 1971

Mutation (TAA>CAA) of termination codonat position 142 of the 2-globin gene

172 amino acids (normal 141)

Unstable mRNA-CS

Milner PF, Lancet 1971


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Hb Constant Spring

Most common in SEA

In Malaysia, most common in Malays

Malays- 2.24% Chinese- 0.66%

Indians- 0.16%

In Bangkok- 1.48%

Wee YC, J Obstet Gynaecol Res 2005



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George E, Hemoglobin 1992

Type of -thal

Ethnicorigin

No.cases

Age (yr)Av

(range)

Hb (g/dL)Av

(range)

HbH (%)Av (range)

- -

SEA

/-

4.2

Chinese 3 28(21- 40) 8.0(7.1- 9.9) 4.0(2.0- 6.1)

- -SEA/- 3.7 Chinese (5)Malay (2)

7 31.5(12- 63)

9.2(8.2- 10.0)

6.7(3.9- 12.1)

- -SEA

/CS

Chinese (5)Malay (8) 13 22.5(6- 35) 8.5(3.4- 10.7) 15.1(4.0- 25.6)

TT Chinese 1 57 10.6 n.d.

Hb H disease, n= 24


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Common thalassaemia syndromes

HbH (- -/- )

HbH-CS (- -/CS)

Hb AE-Barts (- -/- , E)

Hb EF-Barts (- -/- , EE)

Homozygous CS (CS/CS)

Hb Barts hydrops fetalis (- -/- -)


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thalassaemias


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Spectrum of thalassaemia mutations inMalays and Malaysian-Chinese

Malays % Chinese %IVS 1-5 (G>C) 50.0 *Codon 41-42 (-TCTT) 49.8

*IVS 1-1 (G>T) 19.4 IVS 2-654 (C>T) 23.4

*Codon 17 (A>T) 13.9 -28 (A>G) 13.3

*Codon 35 (-C) 8.3 *Codon 17 (A>T) 10.1

*Codon 41-42 (-TCTT) 5.6 *Codon 71-72 (+A) 2.1

IVS 2-654 (C>T) 2.8 -29 (A>G) 1.3

E. George, Thalassemia Carrier Diagnosis in Malaysia, 1998



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Our neighbours



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Deletional -thalassaemia Non-deletional -

thal

-thal

-3.7 -4.2 - - SEA - - FIL - - THAI HbCS HbQS Filipino

deletion

*

Kadazan

dusun

42 0 0 0 0 0 0 16 0

n= 125 33.6% 12.8%

Kadazandusun

Jin-Ai MAT, J Biomed Biotech 2010

*22 B-thalmutations


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Spectrum of thalassaemiamutations in Northern Indians

5 mutations account for > 90%

IVS 1-5 (G>C)

IVS 1-1 (G>T)

del 619 bp

codon 41/42 (-TCTT)

codon 8/9 (+G)

Kazazian HH, EMBO J 1984

Garewal G, BJH 1994


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1. Jammu and Kashmir2. Himachal Pradesh

3. Uttarakhand4. Punjab

5. Haryana6. Uttar Pradesh

7. Rajasthan

15. West Bengal16. Orissa

17. Karnataka

18. Andhra Pradesh19. Kerala

20. Tamil Nadu21. Sikkim

8. Gujarat9. Maharashtra

10. Goa11. Madhya Pradesh

12. Chhattisgarh13. Bihar

14. Jharkhand

22. Meghahrya23. Arurachal Pradesh

24. Assam

25. Nagaland26. Manipur27. Mizoram

28. Tripura

Carrier frequency in India


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Hb E

Mutation at position 26 on the globin gene

Replaces glutamic acid by lysine

Limited to mainland SEA

Borders joining Thailand, Laos andCambodia: Hb E triangle


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Hb E triangle


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Hb Malay

Codon 19 (Asn to Ser) (A>G)

Common in Malays and Southern Thailand

More severe than Hb E

Yang KG, BJH 1989


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Common thalassaemia syndromes

thalassaemia major (00)

thalassaemia intermedia (++)

Hb E thalassaemia (E+, E0)

Compound heterozygous Hb Malay

Compound heterozygous thalassaemia


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Mild + -thal/ HbE Severe + -thal/ HbE

Hb E -28/HbE CD 19/HbE IVS II-654/HbE

IVS 1-5/HbE

No. 39 16 7 13 5

Hb type EE EFA EF+Malay EF EF

Hb (g/dL) 11.4 1.2 9.5 1.5 9.2 2.8 6.6 0.9 7.9 1.0

Hb E (%) 95.2 2.1

57.1 5.9 58.2 3.4 57.5 11.6 52.2 8.0

Hb F (%) 4.8 2.1 10.1 5.6 3.4 1.1 39.2 13.7 47.7 8.0

Comparison of Hb levels and Hbanalysis



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GA()0 and G(A)0- thal

Both reported in Malaysia

G(A)0 found in Cantonese subjects

GA()0 found in Thais

Hb F between 9.9- 16.6%

Trent RJ, BJH 1984



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Patient numbers


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Mytalasemia registry, Sept 2011

Total no. patients = 5115


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1341

540

500


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0

50

100

150

200

x

101



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Affected new births in Malaysia

5% carrier frequency for-thal, 3% for 0-thaland 10% for Hb E

Using Hardy-Weinberg equation for recessively

inherited single gene disorder Taking birth rate at 500,000 births/year

Calculate:

350 homozygote thal births/ year 120 hydrops per year

937 Hb E- thal births/year


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Summary

Thalassaemia is the most common inheritedsingle gene disorder in the world

50% of thalassaemia carriers are in South East

Asia

Thalassaemia syndromes were originallyconfined to the tropics

Changing epidemiology SEAsians are now scattered all over


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Summary

In Malaysia, the Chinese, Malays andindigenous people are commonly affected

Hb E, Hb Malay and Hb Constant Springmore common in Malays

0-thal more common in Chinese


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Summary

The common hemoglobinopathies/thalassaemias in Malaysia are:

thalassaemia major

thalassaemia intermedia

Hb E thalassaemia

Hb H disease

Hb H- Constant Spring


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Summary

With a high prevalence of about 5%, screeningfor thalassaemia should be undertaken

Screen for-thal, 0- thal, Hb E

>50% die by age 30 years

Loss of productivity

Estimated life-time cost: >RM1 million/patient Health burden


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The end

epid hb malaysia

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