Our study identified 440 patients with hemoglobinopathies in the 12000 studied subjects. (Table 1). The overall frequency of hemoglobinopathies was found at 3.6% with an average of nine new individuals per month. Sex ratio M/F was found 1.01 and the average age was 17.5 years ranging from two months to 70 years old.
Out of the 440 hemoglobin disorder’s patients, βS mutation was detected in 308 subjects (70%). 186 of them (42.3%) carried the heterozygous form βA/βS, (sex ratio: 0.95), 87 patients (19.8%) were homozygous βS/βS (sex ratio: 1.02) and 35 patients (8%) (Sex ratio: 1.18) were detected to have an Hb S/β-thalassemia. SCT subjects showed an average of 38.17 ± 4.11% of Hb S with a slight decrease in the Hb A. SCA patients were characterized by the presence of Hb S fraction with an average of 62.96 ± 13.4%, a minor expression of Hb A and a high-level of fetal hemoglobin Hb F (mean value: 17.98 ± 9.39%). The double heterozygosity Hb S/β-thalassemia showed elevated rates of Hb S at 69.39 ± 17.78%, Hb A2 rates of 5.24 ± 1.88% and decreased Hb F levels.
Major β-Thalassemia patients (9.8%) (Sex ratio: 1.38) registered the lowest hemoglobin average and microcytic hypochromic anemia. A significant decrease was observed in Hb A (20.35 ± 14.4%), an increase in Hb A2 and high increase in Hb F levels.
β-Thalassemia trait was present among 89 subjects (20.2%) (Sex ratio: 1.06). They showed milder anemia and a slight decrease of Hb A associated with an increase of both Hb A2 and Hb F compared to normal subjects.
Hematological parameters and hemoglobin variants levels are presented in Table 1.
Regarding patients gender, most of the SCA patients (91/186 patients), major β-Thalassemia (25/43) and the sickle/β-thalassemia subjects (19/35) were males. However, the majority of SCT (42/78) and all four β-thalassemia trait patients were females (Table 1). Out of the 440 patients, 222 (50.5%) were males and 218 (49.5%) were females. This difference was found statistically not significant (χ2 = 0.125, P-value > 0.05).
Table 1
Hematological parameters of different types of hemoglobinopathies in the study subjects.
Hb pattern | Total N(%) | Female N | Male N | Mean age | Hb (g/dL) | Hb A2% | Hb A% | Hb F% | Hb S% | RBC (× 106/µL) | Hct% | MCV (fL) | MCH (pg) | MCHC (g/dL) |
Sickle Cell Trait | 186 (42.3) | 91 | 95 | 22.5 | 10.92 ± 1.71 | 3.23 ± 0.43 | 56.6 ± 5.35 | 10.08 ± 2.16 | 38.17 ± 4.11 | 4.63 ± 0.65 | 35.95 ± 4.9 | 70.48 ± 5.03 | 26.12 ± 3.18 | 33.18 ± 1.25 |
Sickle Cell Anemia | 89 (20.2) | 43 | 46 | 11.7 | 7.86 ± 1.29 | 3.47 ± 1.4 | 5.76 ± 2.38 | 17.98 ± 9.39 | 62.96 ± 13.4 | 2.73 ± 0.78 | 23.53 ± 4.06 | 75.6 ± 10.6 | 27 ± 4.38 | 33.64 ± 1.7 |
β-Thal trait | 87 (19.8) | 44 | 43 | 19.8 | 11.16 ± 1.56 | 5.46 ± 0.56 | 83.43 ± 1.8 | 1.78 ± 0.6 | 0 | 5.59 ± 1.05 | 34.5 ± 4.6 | 63.91 ± 6.64 | 20.4 ± 3.36 | 31.94 ± 0.79 |
β-Thal Major | 43 (9.8) | 25 | 18 | 11.9 | 6.1 ± 2.91 | 5.1 ± 1.08 | 20.35 ± 6.4 | 74.55 ± 8.6 | 0 | 3.89 ± 1.5 | 20.8 ± 4.95 | 65.9 ± 9.1 | 24.05 ± 4.17 | 31.55 ± 2.92 |
Sickle Cell S/β-Thalassemia | 35 (8) | 19 | 16 | 12.9 | 7.45 ± 1.74 | 5.24 ± 1.88 | 12.28 ± 5.19 | 8.09 ± 5.08 | 50.39 ± 17.78 | 3.15 ± 0.67 | 22.68 ± 2.51 | 73.71 ± 7.6 | 24.29 ± 2.34 | 32.9 ± 0.88 |
Values mentioned are mean ± standard deviation. Hb-Hemoglobin, Hb A2-Hemoglobin A2, Hb A-Hemoglobin A, Hb F-Fetal hemoglobin, Hb S-Sickle Hemoglobin, RBC-Red blood cells, Ht-Hematocrit, MCV-Mean corpuscular volume, MCH-Mean corpuscular hemoglobin, MCHC-Mean corpuscular hemoglobin concentration.
Genotypic frequencies of different genotypes in the studied region were calculated. Results are given in Table 2. βS allele frequency was estimated at 1.6%, βThal at 0.9% and the normal allele βA at 97.5%. It was noticed that the observed frequency of SCA (0.73%), major β-thalassemia (0.36%) and the sickle/β-thalassemia (0.29%) was significantly higher than the expected number according to the HWE (0.03%, 0.01% and 0.03% respectively). Among Sickle cell trait, β-thalassemia trait subjects, the calculated genotypic frequency (3.21% and 1.71% respectively) was found significantly higher than the observed frequency (1.55% and 0.74% respectively).
Table 2
Observed and theoretical genotypic frequencies.
| Observed Genotypic frequencies | Theoretical genotypic frequencies |
Genotype | N | % | N | % |
SCT | 186 | 1.55% | 385 | 3.21% |
SCA | 87 | 0.73% | 3 | 0.03% |
β-Thal Major | 43 | 0.36% | 1 | 0.01% |
β-Thal Trait | 89 | 0.74% | 205 | 1.71% |
HbS/β-Thalassemia | 35 | 0.29% | 3 | 0.03% |
AA | 11560 | 96.33% | 11403 | 95.02% |
Total | 12000 | 100% | 12000 | 100% |
Figure 2 presents the age distribution of the different hemoglobinopathies patients. The mean age of SCA, SCT, β-thalassemia major, β-Thalassemia trait and sickle/β-thalassemia patients were 11.7, 22.5, 11.9, 19.8 and 12.9 years, respectively. The onset of the abnormalities was most prominent in childhood period (1–10 years) (164; 37.1%), followed by 10–20 years group (118; 26.7%). Beyond 20 years, the frequency of hemoglobinopathies decreased with age. Newborns group (< 1) present a low rate with 12 patients (2.7%). Others age groups are respectively (66; 14.9%), (45; 10.2%), (22; 5%), (10; 2.3%) and (5; 1.1%) for 20–30, 30–40, 40–50, 50–60 and older than 60 years old.
Based on the hospital records, the majority of the recruited hemoglobinopathies carriers came rural areas (328; 74.5%) compared to patients from urban settings (112; 25.5%).
District wise distribution of the different hemoglobinopathies is shown in Fig. 3. The affected urban areas are Larache city (82; 18.6%) and Ksar El Kbir city (30; 6.8%). In the rural sittings, Laouamra was found to be the most touched (201; 45.7%), followed by Zouada (65; 14.8%), Khmis-Sahel (18; 4.1%) and 10% over the rest of the province. A statistically significant differences (P > 0.05) were found across the hemoglobinopathies in the different districts.