An overview of haemoglobinopathies in Latin American Countries

1. GLOBAL GLOBIN 2020
CHALLENGE
DEVELOPING CAPACITY FOR
VARIANT DATA SHARING IN
LOW & MIDDLE INCOME COUNTRIES
Paris, France, 2016

2. GLOBAL GLOBIN 2020
CHALLENGE
DEVELOPING CAPACITY FOR
VARIANT DATA SHARING IN
LOW & MIDDLE INCOME COUNTRIES
Latin American Countries
Paris, France, 2016

3. 3
HbS AND BETA THALASSEMIA CARRIERS IN LATINAMERICA
País Población
Millones
%
Portadores
HbS
%
Portadores
β-talasemia
Raíces
africanas
Población
General
México 120 12.8 0.45 0.4
Honduras, Nicaragua,
Costa Rica, Panamá
8.7, 6.0,
4.9, 4.0
10.0, 11.1,
10.9, 16.0
NE, NE,
2.5, 7.7
NE, NE,
0.25, NE
Cuba, Haití,
República Dominicana
11.0, 9.8,
10.1
6.1, 13.2,
7.0
1.5, 15.0,
4.8
0.45, 1.0,
1.0
Colombia, Venezuela 48.2, 28.0 11.2, 19.1 2.4, 1.9 0.8, 0.2
Brasil 203.4 6.2 4 1.3
Ecuador, Perú 16.3, 30.8 21.9, NE NE, 3.3 NE, 2.05
Argentina, Uruguay 41.8, 3.3 NE, 10.0 0.7, NE 1.35, NE

4. Countries interested to
participate
in GG2020
4
México
Colombia
Costa Rica
Panamá

5. 5
WHAT IS KNOWN ABOUT THE DISEASE BURDEN IN YOUR COUNTRY?
What are the major health issues related to haemoglobinopathies in your country?
Mexico Sickle cell disease and thalassemias
Colombia Pain crisis in SCD patients, the major cause of hospitalization
Costa Rica Sickle cell disease, beta thal minor and some cases of Cooley’s anemia
Panamá Sickle cell disease and thalassemias
Is there any central reporting of cases?
Mexico No
Colombia No
Costa Rica Yes. A Research Center (CIHATA) (Universidad de Costa Rica) (but it doesn't receive all the cases). It is obligatory the newborn screening on Hb S by
The National Screening Program, supported by the Public Health System (Caja Costarricense del Seguro Social). There is also a Foundation from
patients for additional support (called FUNDREPA)
Panamá Yes. The Health Minister for newborn Screening.
What information is readily available? What is its quality?
Mexico Academic books and national and international papers
Colombia Limited to academic texts like books and papers.
Costa Rica There are different population studies, some with molecular studies, and the first report of the neonatal screening program on HbS.
Panamá Newborn Screening Very confidencial.

6. 6
NATIONAL CO-ORDINATION AND PLANNING
Is there a national co-ordination and planning body for any haemoglobinopathies?
what does it do:
 national epidemiology:
 monitor demand and supply of services:
 public education:
 other?:
Mexico No, there isn’t a national coordination center for haemoglobinopathies
Colombia No, there isn’t a national coordination center for haemoglobinopathies
Costa Rica There is no national coordination. The more precise information on HbS is obtained from the National Screening Program. Not all the samples are se
to the Research Center (CIHATA). Other hospitals do their own diagnosis.
 national epidemiology: population studies by CIHATA and screening program.
 monitor demand and supply of services: each hospital
 public education: by CIHATA and FUNDREPA
 other?
Panamá Is there a national co-ordination and planning body for any haemoglobinopathies?
Yes
what does it do:
 national epidemiology:
 monitor demand and supply of services: yes
 public education: Yes
 other?: Neonatal screening

7. Local contacts
1. México
Dr. Augusto Rojas Martínez (arojasmtz@gmail.com).
Dra. Bertha Ibarra (bibarra@mail.udg.mx).
2. Costa Rica
Dr. Walter Rodríguez (werodrigrom@yahoo.com)
3. Panamá
Dra. Gladys Cossio (gcossio@cableonda.net )
4. Colombia
Dra. Laura Cifuentes (lauracifuentes@gmail.com)
7

8. Countries interested to
participate
in GG2020
8
Brazil
Uruguay
Venezuela

9. 9
HAT IS KNOWN ABOUT THE DISEASE BURDEN IN YOUR COUNTRY?
hat are the major health issues related to haemoglobinopathies in your country?
azil Sickle cell disease and thalassemias. Betha Globin mutations more common.
ruguay Sickle cell anemia and thalassemia
enezuela Sickle cell disease, beta thal minor.
Haemoglobinopathy more frequent HbS, and variants C and D.
there any central reporting of cases?
azil Yes
ruguay Central reporting cases . National Pilote Program for Haemoglobinopathies detection (Dbe 2012) Reference National Laboratorie Banco
Prevision Social.
enezuela Central Reporting cases of Congenital Diseases and rare conditions. Not for haemoglobinopathies. ECLAM.
What information is readily available? What is its quality?
azil National registry of reporting cases Screening programs haemoglobinopathies patients and family members. Genetic Counselling
ruguay National Registry of Congenital Debects and rare diseases )RNDCER)
http://www.msp.gub.uy/marco-normativo/registro- nacional-de- defectos-cong%C3%A9nitos- y-enfermedades- raras
enezuela National registry of reporting cases

10. 10
NATIONAL CO-ORDINATION AND PLANNING
Is there a national co-ordination and planning body for any haemoglobinopathies?
what does it do:
 national epidemiology:
 monitor demand and supply of services:
 public education:
 other?:
Brazil
Is there a national co-ordination and planning body for any haemoglobinopathies?
No, there isn’t a national coordination center for haemoglobinopathies
The Laboratory of Hemoglobinopathies in the Clinical Pathology Department of the Medical Sciences School of the State University
in Campinas - Unicamp, São Paulo, Southeastern Brazil, carried out, in its 27 years of activity, about 130,000 diagnoses. E M
Kimura,2014.
Works specifically looking for genetic risk factors for sickle cell anemia complications, like vasooclusive events (stroke), leg ulcers, sickle
cell retinopathy and pregnancy complications. We have been using microarray analysis,exome sequencing and transcriptome
sequencing as our main strategies
HPLC/RP-HPLCV/multiplex ligation-dependent probe amplification (MLPA) techniques. microarray analysis, exome sequencing and
transcriptome sequencing , Monica Melo
Medical and Human Genetics Laboratory (Laboratório de Genética Humana e Médica - LGHM) at the Federal University of Pará
(Universidade Federal do Pará - UFPA)
In quilombos communities in the Pará state studied variations in HbF levels in sickle cell anemia patients and its interaction with
clinical disease, using HPLC and molecular biology (ABI 7500 Real Time PCR) for the genotyping of previously published SNPs related to
such variations and Molecular characterization of patients with any suspectedhemoglobinopathy , with PCR, multiplex PCR, Real Time
PCR and DNA sequencing and search for mutations that cause variantshemoglobins (S and C), alfa-thalassemia (-3.7, -20.5, -MED and -
SEA), beta-thalassemia (-87, -88, -29, CD6, CD15, IVSI-1, IVSI-5, IVSI-6, ....) and SNPs related to variations in HbFlevels (HBG2, BCL11A,
HBS1-MYB). Our goal is to propose a research to assist disease prognosis and improvepatients’ life quality. João Farias Guerreiro
Graice Cardoso,PhD
Molecular alterations responsible for the alpha-thalassemic phenotypes in 8 unrelated individuals (3 males and 5 females; age, 4
months to 30 years) in whom the molecular basis of the disease could not be determined by conventional methods were detected.
Avariety of rearrangements identified, C.N. Suemasu,2011.

11. 11
NATIONAL CO-ORDINATION AND PLANNING
Is there a national co-ordination and planning body for any haemoglobinopathies?
what does it do:
 national epidemiology:
 monitor demand and supply of services:
 public education:
 other?:
Uruguay 48.000 births per year/ 2 cases yearly.
Inmunoelectroforesis globinas IEF/ HPLC adults ;
No molecular test
Is there a national co-ordination and planning body for any haemoglobinopathies?
No, there isn’t a national coordination center for haemoglobinopathies.
No screening services.
No genetic counselling

12. 12
NATIONAL CO-ORDINATION AND PLANNING
Is there a national co-ordination and planning body for any haemoglobinopathies?
what does it do:
 national epidemiology:
 monitor demand and supply of services:
 public education:
 other?:
Venezuela
In a population study of 80400 individuals from diferent regions of Venezuela with dx of haemolitic anemia:
-76400 by hemoglobin electrophoresis in acetate and citrate agar, solubility tests, family studies and 4000 by cromathography
(HPLC-CE)
9% have Dx of haemoglobinopathy, been the more frequent HbS, and variants C and D. Thalasemia and its relation with Hb S and C
was determined.
Frequency of haplotypes of bs gen in 272 patients with drepanocitosis (SCA) and heterocygotes for HbS was 50, 8% Benin, 32,2%
CAR, 14,2 Senegal y 2,3% Camerun.
In homocygous patients for HbS 8% was homocygous for Ben haplotype, 82% were double heterocygote for haplotypes Ben/CAR,
8,8% presented haplotypes Ben,Senegal,CAR/Senegal y Ben/Camerun and one patient was homocygos for haplotype CA
A Arends et al, Science and Technology,2007, 32;8:516-521

13. 13
NATIONAL CO-ORDINATION AND PLANNING
Is there a national co-ordination and planning body for any haemoglobinopathies?
what does it do:
 national epidemiology:
 monitor demand and supply of services:
 public education:
 other?:
Venezuela
Sickle Cell Disease SCD exhibits a wide spectrum of clinical behaviour, from mild condition to an incapacitating illness
Epidemiological studies: variable frequency, ranging from zero in the Venezuelan indians up to 5% in the Mestizo and Afro-American
population; 12% in the North Central costal Region (Arends,1971; Arends et al 1982).
Seven polymorphic sites in the b-globin gene cluster (State of Aragua).
. Benin haplotype 0.479, Bantu haplotype 0.406; atypical Bantu A2 0.042; Senegal 0.031; atypical Bantu A7
0.021 and Saudi Arabia_Indian (0.021). N Moreno et al, Genet. Mol. Biol. 25,1:2002
Sudanese and Bantu origins for the African slaves brought into Venezuela.
Haematological characteristics and clinical severity related to variations in fetal haemoglobin (HBF) levels (Falusi and
Otalungi,1994);Steimberg,1996), the simultaneous presence of a-thalassemia (Figuereido,et al,1996, Mukherjee et al, 1997) glucose-6-phosphate
dehydrogenase deficiency (Bouanga et al,1998) and the b-globin cluster linked haplotypes (Powars adnHiti,1993 Steinerg 1996).

14. 14
NATIONAL CO-ORDINATION AND PLANNING
Is there a national co-ordination and planning body for any haemoglobinopathies?
what does it do:
 national epidemiology:
 monitor demand and supply of services:
 public education:
 other?:
Venezuela
•101.301 heel blood samples newborns were analysed by high performance liquid chromatography
(HPLC-CE), using Variant Bio Rad System with the Sickle Cell Short program for the filter paper samples and the Beta thak program for family
studies127 unrelated subjects with a suspicion of β- thalassemia trait or with a clinically recognized β-thal syndrome of different degrees of
severity had DNA studies (PCR-bases reverse dot-blot method or amplification refractory mutation system (ARMS).
15 different mutations were identified accounting for the 92% of the mutant alleles studied, revealing a significant genetic heterogeneity at the
β- globin gene locus in this population M Bravo-Urquiola, Hemoglobin,2012;36(3):209-18).
Most frequent mutations:
Codon 39 (C >T) 34.1%, IVS-I-(G >A) 11.1%, IVS-I-6(T >C=6.6%,-29 (A >G) 5.2%.
Less common mutations
IVS-I-5 (G >A) 3.7%
The 1,393 bp deletion 3.0%
IVSII-1 (G >A) 3.0%, -86 (C >G) 2.2% , IVSII-1 (G >T) 1.5%,
(C >T) codons 41/42 (-TCTT) 1.5%, IVSS-II745 (C >G) 0.7% and deletion al ᶳβ- thal 0.7%.
The major sources of β - thal-alleles in Venezuela , as expected, are of Mediterranean and African origins.
Diversity of haplotypes associated with some of the β-thal mutations can be explained by in situ recombination events in Venezuela.
Genetic counseling as well as implementing comprehensive clinical care programs are starting now.
There isn’t a national coordination center for haemoglobinopathies
As In most of the countries the Health Care System is Public. Public Education and Public Health Services. The majority of Genetics Departments
or Units in the region are located in General Universitary Hospitals or Research Institutes. Genetic Counselling is part of the activity of Clinical
Geneticist in the Country.

15. Local contacts
1. Brazil
Dr. Fernando Ferreira Costa, Dr. Sara T. Olalla Saad and Dr. Dulcinéia M. Albuquerque
Hematology and Hemotherapy Center, Faculty of Medical Sciences, University of
Campinas, SP, Brazil Dr. Maria de Fátima Sonati, Dr. Magnun Nueldo Nunes dos Santos
and Dr. Susan Elizabeth Domingues Costa Jorge
Department of Clinical Pathology, Faculty of Medical Sciences, University of Campinas, SP,
Brazil
Dr. Mônica Barbosa de Melo, Human Genetics Laboratory, Center for Molecular
Biology and Genetic Engineering, University of Campinas, SP, Brazil
melomb@unicamp.br
Dra. Greice Cardoso
greice_cardoso@yahoo.com.br
Professor Joao Farias Guerreiro
2. Uruguay
Dra. Mariela Larrandaburu
marielalarrandaburu@gmail.com
3. Venezuela
Dra A. Arends Dra. M Bravo-Urquiola, Dra. Aída Falcón de Vargas
aidafalvar@gmail.com
15

16. Dra. Aída Falcón de Vargas President RELAGH and President VSHG
Dra. Lavinia Schuller Faccini Vice President of RELAGH and President BSMG

17. Thank You