An overview of the health system response to haemoglobinopathies in Pakistan

1. Qasim Ayub
qa1@sanger.ac.uk
Team 19:Human Evolution
http://www.sanger.ac.uk/science/groups/tyler-smith-group
Wellcome Trust Sanger Institute
Wellcome Genome Campus
Hinxton, United Kingdom
Global Globin 2020 Challenge
The Human Variome Project
UNESCO, Paris
May 30, 2016
Haemoglobinopathies in Pakistan
A Review

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Outline
 Pakistan
 Geography
 Demography
 Population Structure
 Haemoglobinoapathies in Pakistan.
 Legislation.
 Moving forward.

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Pakistan

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Balochistan
Pakistan location map.svg (by NordNordWest)
https://commons.wikimedia.org/w/index.php?curid=16496357

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Khyber Pakhtunkhwa (N.W.F.P.)
Pakistan location map.svg (by NordNordWest)
https://commons.wikimedia.org/w/index.php?curid=16496357

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Punjab
Pakistan location map.svg (by NordNordWest)
https://commons.wikimedia.org/w/index.php?curid=16496357

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Sindh
Pakistan location map.svg (by NordNordWest)
https://commons.wikimedia.org/w/index.php?curid=16496357

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Pakistan
The Burden of Haemoglobinopathies
 In Pakistan β-thalassaemia is the most prevalent
among the haemoglobinopathies.
 Published estimates indicate that that the carrier rate
is between 5-7% and that there are approximately 8 - 10
million β-thalassaemia carriers in Pakistan.
 An estimated 5,000-9,000 new cases of β-thalassaemia
are added each year placing a severe socio-economic
burden.
 A rate of 2.4% has been estimated for carriers of alpha-
thalassaemia in the general population in Pakistan.

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Mutation Consequence Phenotype
Allele Frequency
(%)Reference Disease
IVS1-5 Consensus splice site β0 G C 34
Codon 8/9 FRM Frameshift β0 +G 26
619 bp Del Deletion del 10
IVS1-1 Splice junction β0 G T 9
Codon 41/42 FRM Frameshift β0 -TTCT 10
Rare HBB mutations in Pakistan
CD 15
CD5
CD 30 (G > C)
CD 30 (G > A)
CAP+1
Fr16
IVSII-1
β- Thalassaemia in Pakistan
IVS1-5
CD 8/9 FRM
619 bp
IVS1-1
CD41/42
Rare

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Northern Pakistan
IVS1-5
CD 8/9 FRM
CD41/42
n = 1,450
IVS1-5
CD 8/9 FRM
CD41/42n = 537

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Southern Pakistan
IVS1-5
619 bp
n = 270
IVS1-5n = 651

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α- Thalassemia
Deletions Sindh Punjab Khyber Pakhtunkhwa
(NWFP)
Balochistan
-α4.2 
-α3.7   
http://prr.hec.gov.pk/thesis/251S.pdf
[Khan SN, 2003; Galanello, 2011; Piel 2014]
Higgs (2013) Cold Spring Harb Perspect Med 2013;3:a011718

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Genetic Screening and Counselling
 Pre-marital and pre-natal screening offered in few major
urban centres.
 No national coordiantion charitable and non-
governmental organizations.
 Premarital advice/screening is inconsistent and patchy.
 No genetic counselling service exists and patients
usually personally seek advice from their primary health
care provider or physician.

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Legislation
The bill suggests compulsory pre-marriage screening for
β-thalassaemia

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Pakistan Current Status
http://www.genome.gov/sequencingcosts/
Policy 1
No prevention programme (baseline situation)√

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Summary
Centuries of endogamy and high consanguinity
has led to high rates of autosomal recessive
disorders in the Pakistani population, particularly
haemoglobinapathies such as β- thalassaemias.
Molecular characterization reveals that overall five
major mutations account for ~90% of β-
thalassaemia cases. The frequency of these
mutations differs in the major ethic groups.
No overall government policy or disease registry
exists and services are mainly offered by
charitable and non-governmental organizations.
Legislation exists in three of four major
administrative regions of the country, but overall
enforcement is lax.

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Moving Forward
http://www.genome.gov/sequencingcosts/
 Establish a national disease registry.
 Engage and inform public about disease risk.
 Collect molecular epidemiological data from all
ethnicities and geographically regions.
 Screen population at risk for 5 common mutations.
 Enforce existing regulations regarding pre-marital
screening.
 Offer pre-natal diagnosis and genetic counclling
services in all major urban centers.

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Acknowledgements
Human Evolution Team (19)
Hinxton, United Kingdom
Chris Tyler-Smith
Jamil-ur-Rahman Center for Genome Research
University of Karachi
Karachi, Pakistan
Ishtiaq Ahmad Khan
Contact:
qa1@sanger.ac.uk