Global Epidemiology of Haemoglobin Disorders and Derived Service indicators/Epidemiologie Mondiale Des Troubles De L'hemoglobine et Indicateurs De Service derives/Epidemiologia Mundial De Las Hemoglobinopatias E Indicadores De Los Servicios Correspondientes (2008)

Introduction Inherited haemoglobin disorders (sickle-cell disorders and thalassaemias) were originally characteristic of the tropics and subtropics but are now common worldwide due to migration. (1-4) Since they can be controlled cost-effectively by programmes that integrate treatment with carrier detection and genetic counselling, WHO has recommended global development of these services. (5,6) However, service development can be unexpectedly challenging, because it requires inclusion of genetic approaches in health systems. The diversity and heterogeneous distribution of haemoglobin disorders make it necessary to develop strategies at the country level. To assist policymakers, we use haemoglobin disorders as an example to show how genetic epidemiological data can be interpreted in terms of administrative boundaries (and/or ethnic group) and practical service indicators. The work was initiated for WHO (7,8) and further developed in the United Kingdom, (9,10) where it is used for local needs-assessment. (11) Global data are available at: www. chime.ucl.ac.uk/work-areas/cab/. Genetic terminology can be impenetrable to non-specialists. In this paper, we use terms proposed for more general use by the Professional Education for Genetic Assessment and Screening (PEGASUS) Genetic Education Programme of the United Kingdom National Screening Committee: (11) haemoglobin disorders include sickle-cell disorders and thalassaemias; haemoglobin gene variants are haemoglobinopathies; significant variants are gene variants that can cause a serious disorder; carriers are healthy heterozygotes; people with combinations of gene variants are homozygotes and compound heterozygotes; and [alpha] thalassaemia major is haemoglobin Barts hydrops fetalis. Genetic background Haemoglobin comprises four globin chains: fetal haemoglobin (Hb F) has two [alpha] and two gamma chains ([[alpha].sub.2] [[gamma].sub.2]) and adult haemoglobin (Hb A) has two [alpha] and two [beta] chains ([[alpha].sub.2][[beta].sub.2]). Genes in the [alpha]-globin and [beta]-globin gene clusters (on chromosomes 16 and 11) control globin-chain production. Due to spontaneous mutation, haemoglobin gene variants are present at low prevalence (carriers 1-1.5/1000) in all sizeable populations. (2,12) They fall into two broad groups--structural variants that change the amino acid sequence and produce an unusual haemoglobin, (13) and thalassaemias that lower or abolish production of globin chains. (14) Most haemoglobin gene variants are rare and many are harmless, but some are common because carriers are less likely than others to die from falciparum malaria. The most common such variant, or plus ([[alpha].sup.+]) thalassaemia, is usually harmless. However, people who inherit combinations of haemoglobins S, C, E, D Punjab, [beta] thalassaemia, or [alpha] zero ([[alpha].sup.0]) thalassaemia may have a serious haemoglobin disorder. In populations in which malaria is (or was) endemic, 3 to 40% of individuals carry one of these significant variants, and the prevalence of haemoglobin disorders ranges from 0.3 to 25 per 1000 live births. (8) Carriers are easily detected by routine haematological methods and can be forewarned of their reproductive risk. Carriers of structural variants have 30-50% of the variant haemoglobin in their red cells: thalassaemia carriers have small red blood cells and sometimes mild anaemia, (3) and [beta] thalassaemia carriers also have over 3.5% of Hb [A.sub.2]. The resemblance between thalassaemia and iron deficiency can confuse the diagnosis of either disorder. (15) Requirements for treatment [beta] thalassaemia major causes profound anaemia that kills untreated affected children before the age of 3 years. However, the life expectancy of patients treated with regular blood transfusion and iron-chelation therapy, or bone-marrow transplantation, is approaching normal. (16,17) [alpha] thalassaemia major causes hydrops fetalis and perinatal death, often with life-threatening obstetric complications for the mother, (3) and prenatal diagnosis usually leads to termination of pregnancy. …