Newborn screening for abnormal haemoglobins in Jamaica: Practical issues in an island programme.

OBJECTIVE: To report the diagnostic challenges of newborn screening for abnormal haemoglobins. SETTING: Cord blood samples from 13 hospitals in southwest Jamaica taken in 2008-2019. METHODS: Blood spots, collected from the umbilical cord, were analysed by high pressure liquid chromatography (HPLC) to reveal phenotypes for HbSS and HbCC, but genotype confirmation may require parental studies or gene sequencing. Such cases that were successfully traced were analysed in this follow-up study. RESULTS: HPLC screening of 121,306 samples detected HbAS in 11,846 (9.8%), HbAC in 4508 (3.7%) and other electrophoretic abnormalities in 1090 babies. Among 101 previously unconfirmed cases, 34/90 (38%) with HPLC evidence of a HbSS phenotype had other genotypes, and 7/11 (64%) with a HbCC phenotype had other genotypes. Syndromes from the interaction of ß thalassaemia occurred in 112 babies (85 with HbS, 27 with HbC) and of genes for hereditary persistence of fetal haemoglobin (HPFH) in 18 (12 with HbS, 6 with HbC). Variants other than HbS and HbC occurred in 270 babies, 16 in combination with either HbS or HbC, and 254 as traits. Most variants are benign even when inherited with HbS, although HbO Arab, HbD Punjab, or Hb Lepore Washington, which occurred in 6 cases, may cause sickle cell disease. CONCLUSIONS: Genes for ß thalassaemia and HPFH are common in western Jamaica and when associated with HbS may present diagnostic challenges in newborns, as HbF and HbA2 have not reached diagnostic levels. Family and DNA studies may be necessary for genotype confirmation.

Prevention of sickle cell disease: observations on females with the sickle cell trait from the Manchester project, Jamaica.

Screening for haemoglobin genotype was offered to senior school students in Manchester parish in south central Jamaica to test whether this knowledge would influence choice of partner and reduce births with sickle cell disease. Over six academic years, 15,539 students, aged mostly 15-19 years, were screened with voluntary compliance rising from 56 to 92 % over this period. All subjects were given permanent genotype cards and carriers of abnormal genes were offered counselling which explained the reproductive options but avoided recommendations. Prior to screening, all had been offered illustrated lectures on the genetics and clinical features of sickle cell disease. The current study, confined to females with the sickle cell trait, interviewed 763/845 (90.3 %) subjects seeking to assess retention of this knowledge and their response to subsequent boyfriends. Of those interviewed, 42 subjects were excluded (38 emigrated, one died, three received incorrect genotype cards) leaving 721 with complete information. Knowledge of genotype was retained in 95 %, the outcome of future offspring correctly recalled in 91 %, and haemoglobin genotype cards were still possessed by 89 %. A current 'boyfriend' was acknowledged in 403 (56 %) of whom the partner's genotype was known in 88 (74 determined by the project laboratory; 14 by other laboratories) and unknown in 315 (78 %). Offers of free blood tests to all these partners were accepted by only 14 (4 %). Seventeen (2.4 %) were married but the husbands genotype was known in only five (four AA, one AS) of these. Most subjects retain knowledge of their genotype and of its significance for having affected children but the reluctance of partners to be tested was a major obstacle.

Screening for the beta-thalassaemia trait: hazards among populations of West African Ancestry.

The aim of this study was to examine the accuracy and characteristics of detecting the beta-thalassaemia trait in populations of West African ancestry. School children, aged 16-19 years, in Manchester Parish, Jamaica were screened to detect the genes which could give rise to offspring with sickle cell disease. Haematological indices and HbA(2) levels in subjects with an MCH ≤ 26 pg and an RDW < 18.0 with DNA analysis in those with indices consistent with the beta thalassaemia trait were measured. The performance of published discriminant indices in distinguishing iron deficiency and beta-thalassaemia trait in this population was assessed. Of 10,148 subjects, 1,739 (17.1%) had an AA haemoglobin phenotype and red cell indices consistent with beta-thalassaemia (MCH values ≤ 26 pg, RDW < 18.0) requiring estimations of HbA(2) levels. HbA(2) levels were ≥3.5% in 112 and beta-thalassaemia mutations were identified in 77 of these including the -88 C>T mutation in 35 (45%), -29 A>G in 19 (25%), -90 C>T in 7 (9%), the IVS II-849 A>G in 5 (6%) with smaller contributions from five other mutations. Discriminant indices performed poorly in the differentiation of iron deficiency and the beta-thalassaemia trait. Detection of the beta-thalassaemia trait is relatively insensitive in populations of West African ancestry partly because of the mild defects characterising beta-thalassaemia in this population and also the high prevalence of deletional alpha thalassaemia. More sensitive indicators are required for beta-thalassaemia detection to inform such populations at risk of offspring with sickle cell disease.