Hematological parameters, globin and KLF1 genotypes in Thai families with unusual forms of hereditary hemolytic anemia
| Cases . | Sex . | Age (y, mo) . | Hb (g/dL) . | Hct (%) . | RBC (×106/μL) . | MCV (fL) . | MCH (pg) . | MCHC (g/dL) . | RDW (%) . | Retic. (%) . | NRBC (/100WC) . | Hemoglobin typing (%) . | Globin genotypes . | KLF1 genotypes . | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Hb A . | Hb F . | HbA2/E . | Hb Portland-1 . | Hb Bart's . | αα/αα . | β/β . | Allele 1 . | Allele 2 . | ||||||||||||
| Family A | ||||||||||||||||||||
| P1 | F | 4* | 3.0 | 8.5 | 1.06 | 80.1 | 28.1 | 35.1 | 16.2 | 6.0 | 248 | 70.1 | 16.2 | 3.1 | ND | ND | αα/αα | β/β | R331W | G335R |
| 6.2† | 6.9 | 25.1 | 2.36 | 106.2 | 29.1 | 27.4 | 19.0 | 16.0 | 1510 | 38.5 | 51.8 | 2.0 | 4 | 2 | ||||||
| Father | M | 37 | 13.4 | 40.8 | 4.56 | 89.5 | 29.3 | 32.7 | 13.3 | 2.0 | 0 | 82.3 | 1.5 | 2.7 | 0 | 0 | αα/αα | β/β | W | G335R |
| Mother | F | 34 | 12.2 | 37.4 | 4.69 | 79.7 | 26.0 | 32.6 | 13.5 | 1.0 | 0 | 82.5 | 3.0 | 2.7 | 0 | 0 | αα/αα | β/β | R331W | W |
| Family B | ||||||||||||||||||||
| P2 | M | 0.6‡ | 5.9 | 18.2 | 2.76 | 65.9 | 21.4 | 32.4 | NA | 5.0 | 26 | 72.3¶ | 16.6 | 3 | 8.1§ | 0 | −SEA/αα | βE/β | G176RfsX179 | R301H |
| 12‖ | 7.5 | 25.7 | 3.72 | 69.1 | 20.1 | 29.1 | 17.8 | 9.0 | 181 | 16.9 | 39.1 | 4.3 | 16.2 | 14.7 | ||||||
| Father | M | 36 | 15.6 | 46.3 | 5.88 | 78.8 | 26.5 | 33.6 | 13.6 | 0.5 | 0 | 65.1 | 3.6 | 2.0 | 0 | 0 | αα/αα | β/β | W | R301H |
| Mother | F | 23** | 11.4 | 37 | 6.41 | 57.1 | 17.8 | 30.9 | ND | ND | 0 | 74.9 | 3.4 | 21.7 | 0 | 0 | −SEA/αα | βE/β | G176RfsX179 | W |
| Brother | M | 10 | 12.5 | 37.8 | 5.67 | 66.7 | 22.1 | 33.1 | 17.4 | 1.0 | 0 | 54.0 | 6.9 | 26.9 | 0 | 0 | αα/αα | βE/β | G176RfsX179 | W |
| Family C | ||||||||||||||||||||
| P3 | M | 0.2 | 5.2 | 19.0 | NA | 74.0 | 21.0 | 28.0 | 26.0 | 11.0 | 124 | ND | ND | ND | ND | ND | αα/αα | βE/βE | −154C/T | A298P |
| 1.10†† | 7.7 | 24.5 | 3.35 | 73.1 | 23.0 | 31.4 | 26.2 | 14.0 | 57 | 21.0 | 52.8 | 22.7 | + | + | ||||||
| Father | M | 31 | 14.0 | 42.1 | 5.45 | 77.3 | 25.7 | 33.3 | 14.5 | 1.0 | 0 | 68.4 | 0.5‡‡ | 31.1 | 0 | 0 | αα/αα | βE/β | W | A298P |
| Mother | F | 32 | 11.6 | 35.1 | 5.0 | 70.4 | 23.2 | 33.0 | 14.4 | 0.5 | 0 | 72.0 | 4.3‡‡ | 23.5 | 0 | 0 | αCSα/αα | βE/β | −154C/T | W |
| Family D | ||||||||||||||||||||
| P4 | M | 1.2¶¶ | 6.5 | 21.1 | 2.98 | 70.6 | 21.7 | 30.7 | 37.1 | 10.0 | 100 | 78.7 | 5.5 | 8.3 | 7.3 | 0.2 | −SEA/-α3.7 | βE/β | Q58X | A298P |
| 5.4§§ | 6.6 | 21.5 | 3.09 | 69.5 | 21.4 | 30.9 | 24.3 | 5.0 | 49 | 70 | 2.6 | 9.5 | 17.6 | 0.3 | ||||||
| Father | F | 28 | 14.0 | 42.5 | 6.98 | 60.9 | 20.1 | 32.9 | 17.2 | 1.5 | 0 | 75 | 2.6 | 22.4 | 0 | 0 | −SEA/αα | βE/β | Q58X | W |
| Mother | M | 27 | 12.1 | 34.6 | 4.81 | 72.0 | 25.2 | 35 | 15.5 | 1.0 | 0 | 70.2 | 1.8 | 28 | 0 | 0 | αα/-α3.7 | βE/β | W | A298P |
| Family E | ||||||||||||||||||||
| P5 | M | 18‖‖ | 3.4 | 11.1 | 1.37 | 81.0 | 24.8 | 30.6 | 25.4 | 10.1 | 113 | 62.7 | 29.0 | 4.6 | 10.2 | 6.0 | αα/αα | β/β | G176RfsX179 | A298P |
| 23*** | 8.2 | 27.4 | 3.38 | 81.1 | 24.2 | 29.9 | 22.4 | 6.0 | 86 | |||||||||||
| Father | M | 58 | 14.4 | 43.7 | 5.4 | 81.0 | 26.6 | 33.0 | 14.6 | 1.0 | 0 | 82.8 | 0.9 | 3.8 | 0 | 0 | −α3.7/αα | β/β | W | A298P |
| Mother | F | 55 | 14.1 | 42.7 | 4.85 | 88.0 | 29.1 | 33.1 | 13.9 | 1.0 | 0 | 82.8 | 3.1 | 2.8 | 0 | 0 | αα/αα | β/β | G176RfsX179 | W |
| Family F | ||||||||||||||||||||
| P6 | F | 0.9††† | 6.6 | 21.0 | 2.94 | 71.0 | 22.3 | 31.3 | 23.8 | 10.0 | 8 | 33.3 | 49.8 | 2.4 | 13.7 | 0.8 | αCSα/αα | β/β | G176RfsX179 | A298P |
| 5.7‡‡‡ | 8.3 | 27.1 | 3.82 | 70.9 | 21.6 | 30.5 | 23.4 | 10.0 | 13 | 45.0 | 50.0 | 3.0 | + | + | ||||||
| Father | M | 34 | 13.2 | 40.1 | 5.5 | 73.0 | 24.0 | 32.9 | 14.4 | 6.0 | 0 | 83.0 | 0.2 | 2.7 | 0 | 0 | αCSα/αα | β/β | W | A298P |
| Mother | F | 30 | 13.9 | 41.5 | 5.2 | 80.0 | 26.6 | 33.5 | 14.4 | 2.0 | 0 | 94.8 | 2.4 | 2.8 | 0 | 0 | αα/αα | β/β | G176RfsX179 | W |
| Brother 1 | M | 11 | 11.8 | 36.7 | 5.2 | 70.4 | 22.7 | 32.3 | 15.1 | 1.0 | 0 | 96.4 | 0.5 | 3.1 | 0 | 0 | αCSα/αα | β/β | G176RfsX179 | W |
| Brother 2 | M | 8 | 11.7 | 35.1 | 4.7 | 75.4 | 25.1 | 33.3 | 15.1 | 1.0 | 0 | 94.9 | 2.4 | 2.7 | 0 | 0 | αα/αα | β/β | W | A298P |
| Family G | ||||||||||||||||||||
| P7 | M | 0.2¶¶¶ | 5.7 | 17.8 | 2.66 | 67.0 | 21.2 | 31.9 | 21.9 | 11.0 | 146 | 33.9 | 54.6 | 2.2 | 14.3 | 0.3 | −α3.7/αα | β/β | G176RfsX179 | A298P |
| Mother | F | 22 | 11.9 | 36.4 | 4.59 | 79 | 26.0 | 32.8 | 14.4 | 1.0 | 0 | 85.8 | 0 | 2.6 | 0 | 0 | −α3.7/αα | β/β | G176RfsX179 | W |
| Family H | ||||||||||||||||||||
| P8 | M | 4§§§ | 5.4 | 16.3 | 2.18 | 75.0 | 24.7 | 33.1 | 20.4 | 10 | 26 | 69.0 | 19.0 | 10.0 | + | + | αα/αα | βE/β | G176RfsX179 | A298P |
| Father | M | 32 | 13.5 | 45.2 | 5.1 | 66.0 | 19.9 | 29.9 | 16.1 | 2.0 | 0 | 95.9 | 0.9 | 3.2 | 0 | 0 | −SEA/αα | β/β | W | A298P |
| Mother | F | 30 | 12.7 | 40.7 | 5.53 | 74.0 | 23.0 | 31.5 | 15.1 | 2.0 | 0 | 66.6 | 4.7 | 28.7 | 0 | 0 | αα/αα | βE/β | G176RfsX179 | W |
| Cases . | Sex . | Age (y, mo) . | Hb (g/dL) . | Hct (%) . | RBC (×106/μL) . | MCV (fL) . | MCH (pg) . | MCHC (g/dL) . | RDW (%) . | Retic. (%) . | NRBC (/100WC) . | Hemoglobin typing (%) . | Globin genotypes . | KLF1 genotypes . | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Hb A . | Hb F . | HbA2/E . | Hb Portland-1 . | Hb Bart's . | αα/αα . | β/β . | Allele 1 . | Allele 2 . | ||||||||||||
| Family A | ||||||||||||||||||||
| P1 | F | 4* | 3.0 | 8.5 | 1.06 | 80.1 | 28.1 | 35.1 | 16.2 | 6.0 | 248 | 70.1 | 16.2 | 3.1 | ND | ND | αα/αα | β/β | R331W | G335R |
| 6.2† | 6.9 | 25.1 | 2.36 | 106.2 | 29.1 | 27.4 | 19.0 | 16.0 | 1510 | 38.5 | 51.8 | 2.0 | 4 | 2 | ||||||
| Father | M | 37 | 13.4 | 40.8 | 4.56 | 89.5 | 29.3 | 32.7 | 13.3 | 2.0 | 0 | 82.3 | 1.5 | 2.7 | 0 | 0 | αα/αα | β/β | W | G335R |
| Mother | F | 34 | 12.2 | 37.4 | 4.69 | 79.7 | 26.0 | 32.6 | 13.5 | 1.0 | 0 | 82.5 | 3.0 | 2.7 | 0 | 0 | αα/αα | β/β | R331W | W |
| Family B | ||||||||||||||||||||
| P2 | M | 0.6‡ | 5.9 | 18.2 | 2.76 | 65.9 | 21.4 | 32.4 | NA | 5.0 | 26 | 72.3¶ | 16.6 | 3 | 8.1§ | 0 | −SEA/αα | βE/β | G176RfsX179 | R301H |
| 12‖ | 7.5 | 25.7 | 3.72 | 69.1 | 20.1 | 29.1 | 17.8 | 9.0 | 181 | 16.9 | 39.1 | 4.3 | 16.2 | 14.7 | ||||||
| Father | M | 36 | 15.6 | 46.3 | 5.88 | 78.8 | 26.5 | 33.6 | 13.6 | 0.5 | 0 | 65.1 | 3.6 | 2.0 | 0 | 0 | αα/αα | β/β | W | R301H |
| Mother | F | 23** | 11.4 | 37 | 6.41 | 57.1 | 17.8 | 30.9 | ND | ND | 0 | 74.9 | 3.4 | 21.7 | 0 | 0 | −SEA/αα | βE/β | G176RfsX179 | W |
| Brother | M | 10 | 12.5 | 37.8 | 5.67 | 66.7 | 22.1 | 33.1 | 17.4 | 1.0 | 0 | 54.0 | 6.9 | 26.9 | 0 | 0 | αα/αα | βE/β | G176RfsX179 | W |
| Family C | ||||||||||||||||||||
| P3 | M | 0.2 | 5.2 | 19.0 | NA | 74.0 | 21.0 | 28.0 | 26.0 | 11.0 | 124 | ND | ND | ND | ND | ND | αα/αα | βE/βE | −154C/T | A298P |
| 1.10†† | 7.7 | 24.5 | 3.35 | 73.1 | 23.0 | 31.4 | 26.2 | 14.0 | 57 | 21.0 | 52.8 | 22.7 | + | + | ||||||
| Father | M | 31 | 14.0 | 42.1 | 5.45 | 77.3 | 25.7 | 33.3 | 14.5 | 1.0 | 0 | 68.4 | 0.5‡‡ | 31.1 | 0 | 0 | αα/αα | βE/β | W | A298P |
| Mother | F | 32 | 11.6 | 35.1 | 5.0 | 70.4 | 23.2 | 33.0 | 14.4 | 0.5 | 0 | 72.0 | 4.3‡‡ | 23.5 | 0 | 0 | αCSα/αα | βE/β | −154C/T | W |
| Family D | ||||||||||||||||||||
| P4 | M | 1.2¶¶ | 6.5 | 21.1 | 2.98 | 70.6 | 21.7 | 30.7 | 37.1 | 10.0 | 100 | 78.7 | 5.5 | 8.3 | 7.3 | 0.2 | −SEA/-α3.7 | βE/β | Q58X | A298P |
| 5.4§§ | 6.6 | 21.5 | 3.09 | 69.5 | 21.4 | 30.9 | 24.3 | 5.0 | 49 | 70 | 2.6 | 9.5 | 17.6 | 0.3 | ||||||
| Father | F | 28 | 14.0 | 42.5 | 6.98 | 60.9 | 20.1 | 32.9 | 17.2 | 1.5 | 0 | 75 | 2.6 | 22.4 | 0 | 0 | −SEA/αα | βE/β | Q58X | W |
| Mother | M | 27 | 12.1 | 34.6 | 4.81 | 72.0 | 25.2 | 35 | 15.5 | 1.0 | 0 | 70.2 | 1.8 | 28 | 0 | 0 | αα/-α3.7 | βE/β | W | A298P |
| Family E | ||||||||||||||||||||
| P5 | M | 18‖‖ | 3.4 | 11.1 | 1.37 | 81.0 | 24.8 | 30.6 | 25.4 | 10.1 | 113 | 62.7 | 29.0 | 4.6 | 10.2 | 6.0 | αα/αα | β/β | G176RfsX179 | A298P |
| 23*** | 8.2 | 27.4 | 3.38 | 81.1 | 24.2 | 29.9 | 22.4 | 6.0 | 86 | |||||||||||
| Father | M | 58 | 14.4 | 43.7 | 5.4 | 81.0 | 26.6 | 33.0 | 14.6 | 1.0 | 0 | 82.8 | 0.9 | 3.8 | 0 | 0 | −α3.7/αα | β/β | W | A298P |
| Mother | F | 55 | 14.1 | 42.7 | 4.85 | 88.0 | 29.1 | 33.1 | 13.9 | 1.0 | 0 | 82.8 | 3.1 | 2.8 | 0 | 0 | αα/αα | β/β | G176RfsX179 | W |
| Family F | ||||||||||||||||||||
| P6 | F | 0.9††† | 6.6 | 21.0 | 2.94 | 71.0 | 22.3 | 31.3 | 23.8 | 10.0 | 8 | 33.3 | 49.8 | 2.4 | 13.7 | 0.8 | αCSα/αα | β/β | G176RfsX179 | A298P |
| 5.7‡‡‡ | 8.3 | 27.1 | 3.82 | 70.9 | 21.6 | 30.5 | 23.4 | 10.0 | 13 | 45.0 | 50.0 | 3.0 | + | + | ||||||
| Father | M | 34 | 13.2 | 40.1 | 5.5 | 73.0 | 24.0 | 32.9 | 14.4 | 6.0 | 0 | 83.0 | 0.2 | 2.7 | 0 | 0 | αCSα/αα | β/β | W | A298P |
| Mother | F | 30 | 13.9 | 41.5 | 5.2 | 80.0 | 26.6 | 33.5 | 14.4 | 2.0 | 0 | 94.8 | 2.4 | 2.8 | 0 | 0 | αα/αα | β/β | G176RfsX179 | W |
| Brother 1 | M | 11 | 11.8 | 36.7 | 5.2 | 70.4 | 22.7 | 32.3 | 15.1 | 1.0 | 0 | 96.4 | 0.5 | 3.1 | 0 | 0 | αCSα/αα | β/β | G176RfsX179 | W |
| Brother 2 | M | 8 | 11.7 | 35.1 | 4.7 | 75.4 | 25.1 | 33.3 | 15.1 | 1.0 | 0 | 94.9 | 2.4 | 2.7 | 0 | 0 | αα/αα | β/β | W | A298P |
| Family G | ||||||||||||||||||||
| P7 | M | 0.2¶¶¶ | 5.7 | 17.8 | 2.66 | 67.0 | 21.2 | 31.9 | 21.9 | 11.0 | 146 | 33.9 | 54.6 | 2.2 | 14.3 | 0.3 | −α3.7/αα | β/β | G176RfsX179 | A298P |
| Mother | F | 22 | 11.9 | 36.4 | 4.59 | 79 | 26.0 | 32.8 | 14.4 | 1.0 | 0 | 85.8 | 0 | 2.6 | 0 | 0 | −α3.7/αα | β/β | G176RfsX179 | W |
| Family H | ||||||||||||||||||||
| P8 | M | 4§§§ | 5.4 | 16.3 | 2.18 | 75.0 | 24.7 | 33.1 | 20.4 | 10 | 26 | 69.0 | 19.0 | 10.0 | + | + | αα/αα | βE/β | G176RfsX179 | A298P |
| Father | M | 32 | 13.5 | 45.2 | 5.1 | 66.0 | 19.9 | 29.9 | 16.1 | 2.0 | 0 | 95.9 | 0.9 | 3.2 | 0 | 0 | −SEA/αα | β/β | W | A298P |
| Mother | F | 30 | 12.7 | 40.7 | 5.53 | 74.0 | 23.0 | 31.5 | 15.1 | 2.0 | 0 | 66.6 | 4.7 | 28.7 | 0 | 0 | αα/αα | βE/β | G176RfsX179 | W |
Data of hemoglobin (Hb) analyses showed here derived from liquid chromatography in which HbA2 and Hb E were eluted at the same window and could not separate based on this methodology. Hb Portland-1 (ζ2γ2) and Hb Bart’s (γ4) have not been quantified in every patient (supplemental Table 1 and associated clinical text). Individuals without globin gene mutations are highlighted in gray.
F, female; M, male; MCH, mean cell hemoglobin; MCHC, mean cell hemoglobin concentration; MCV, mean corpuscular volume; NA, not available; ND, not determined; RDW, red cell distribution width; P, patient; Retic., reticulocyte count; W, wild type for KLF1 gene sequences.
This study was done when this patient was first referred to our hospital and 2 months after the last blood transfusion.
This study was performed 1 year after splenectomy and when the patient was free from blood transfusion. Of note, P1 is the only patient with a normal MCH (28 pg), suggesting that the coinheritance of thalassemia makes a significant contribution to the defects in Hb synthesis seen in our patients.
This study was performed when the patient (P2) was first seen at our hospital in 1997 at age 6 months.
The patient received less than 1 month of blood transfusion before this study and has been on regular transfusion since.
At first diagnosis, this abnormal hemoglobin was identified as Hb Bart’s.
This study was performed 6 months after splenectomy.
The mother of P2 died of lung cancer on February 18, 2004.
The patient was withheld from regular blood transfusion for 4 months before this study.
HbF measurements were variable even within the same individual; at 2 years before this study, the Hb F levels in the mother and the father were 1.5% and 1.2%, respectively by low-pressure liquid chromatography (LPLC; same laboratory). Moreover, the Hb F levels measured were different based on the techniques used; in the mother, Hb F levels were 4.3%, 3.4%, and 3.3%, and those of the father were 0.5%, 0.9%, and 0%, based on LPLC, high-performance liquid chromatography, and capillary electrophoresis, respectively. Using capillary electrophoresis, we were able to discriminate between Hb E and HbA2; interestingly, the levels of HbA2 in the mother were 3.8% (with 20.8% Hb E) compared with 5.4% (with 26.1% Hb E) in the father. In addition, 0.2% of Hb Constant Spring eluted at retention time 305 s was identified in the mother.
This study was done 2 months after blood transfusion, when this patient was first referred.
This study was performed 3 months after the regular blood transfusion was held.
This study was performed when this patient was withheld from blood transfusion for 10 weeks.
This study was performed 6 months after splenectomy.
This study was performed when this patient first presented at our hospital.
This study was performed after the patient was free from blood transfusion for 2 years.
This study was performed when this patient first presented at age 2 months.
This evaluation was done when the patient was first referred to our center, and the last blood transfusion was performed around 12 weeks before this study.