Genotype–phenotype correlation among beta-thalassemia and beta-thalassemia/HbE disease in Thai children: predictable clinical spectrum using genotypic analysis

Figures & data

Table 1 Patient characteristics

Patient characteristics	Homozygous/compound heterozygous beta-thalassemia major, n = 7 (%)	Beta-thalassemia/HbE, n = 63 (%)	p-value
Sex (%)
Male	5 (71.4)	41 (65.1)	1.000
Female	2 (28.6)	22 (34.9)
Age at onset of anemia (years)	0.8±0.49	3.43±3.5	< 0.001^*
Age at present (years)	14.61±5.13	13.64±5.96	0.681
Weight (kg)	42.09±17.55	37.83±17.29	0.540
Height (cm)	144±21.46	141.65±25.31	0.814
Blood transfusion required (per year)	11.83±2.19	9.67±4.03	0.281
Splenectomy (no. of patients) (%)	5 (71.4)	15 (25.0)	0.021^*
Age at splenectomy (years)	5.3±1.3	7.4±2.5	0.251

Notes: Data shown as mean±SD or number (%). p-value from the t-test or chi-square test for data with a parametric distribution and the Mann–Whitney U-test or Fisher exact test for non-parametric distribution. p<0.05 = statistically significant.

Table 2 The distribution of beta-globin gene (HBB) mutations

Type of mutations	Number of alleles, n (%)
HBB:c.79G>A	63 (45)
[Codon 26 (G>A) or Hb E]
HBB:c.126_129delCTTT	34 (23.8)
[Codon 41/42 (-TCTT)]
HBB:c.52A>T	16 (11.2)
[Codon 17 (A>T)]
HBB:c.92+5G>C	7 (5)
[IVS-I-5 (G>C)]
HBB:c.316-197C>T	5 (3.5)
[IVS-II-654 (C>T)]
HBB:c.108C>A	4 (2.8)
[codon 35 (C>A)]
HBB:c.216_217insA	2 (1.4)
[codon 71/72 (+A)]
HBB:c.92+1G>T	4 (2.8)
[IVS-I-1(G>T)]
3.4 kb deletion	2 (1.4)
HBB:c.59A>G	1 (0.7)
[codon 19 (A>G) or Hb Malay]
HBB:c.2T>G	1 (0.7)
[initial codon (ATG>AGG)]
HBB:c.-78A>G	1 (0.7)
[nt -28 (A>G)]
Total	140 (100)

Table 3 Genotype and hematologic data of beta-thalassemia/HbE patients

Parameter	Beta-thalassemia/HbE
	HBB: c.126_129 delCTTT [Codon 41/42 (-TCTT)]	HBB: c.52A>T [Codon 17 (A>T)]	HBB:c.92+ 5G>C [IVS-I-5 (G>C)]	HBB:c.316-197C>T [IVS-II-654 (C>T)]	HBB: c.108C>A [codon 35 (C>A)]	HBB: c.216_217 insA [codon 71/72 (+A)]	3.4 Kb deletion	HBB: c.59A>G [codon 19 (A>G) or Hb Malay]	HBB:c.-78A>G [nt -28 (A>G)]	HBB:c. 92+1G>T [IVS-I-1(G>T)]
	(n = 28)	(n = 12)	(n = 6)	(n = 5)	(n = 3)	(n = 1)	(n = 2)	(n = 1)	(n = 1)	(n = 4)
Severity
Major	27	12	6	5	3	1	2	–	–	3
Intermedia	1	–	–	–	–	–	–	1	1	1
Splenectomy (no. of patients)	7 (25.9)	3 (25)	1 (16.7)	3 (60)	1 (35)	–	–	–	–	–
Age at present (years)	14.64±5.9	10.84±5.62	14.07±7.53	17.22±3.41	18±3.39	8.9	7.6	5.7	7.7	14.2±6.2
Age at onset of anemia (years)	3.28±2.73	2.33±2.38	5.4±6.52	2.74±2.62	1.87±1	1.8	1.6	0.6	5	8.55±5.79
RBC × 16^12/L	3.53±0.6	3.59±0.57	3.69±0.87	3.46±0.45	3.6±0.19	4.16	4.36±0.77	4.9	3.65	3.87±0.24
Hb (g/dL)	7.48±1.24	7.83±1.38	7.58±1.42	7.94±0.65	8.17±1.1	8.3	9.9±0.71	8.9	8.2	8.13±0.34
HCT (%)	22.92±3.46	23.88±4.19	23.33±3.43	23.72±3.71	25.63±4.38	26	29.45±0.64	26.7	24.9	25.5±1.48
MCV (fL)	63.56±6.74	59.83±8.07	62.15±8.66	67.48±3.41	58.9±1.95	62.5	59.55±2.19	54.4	64.5	64.3±2.71
MCH (pg)	20.87±3.06	20.13±2.76	20.72±2.79	22.36±0.58	23.6±7.97	20	19.8±1.98	18.1	21.2	20.48±1.36
MCHC (g/dL)	32.58±1.72	33.39±1.31	33.2±1.26	32.5±1.47	31.67±1.89	32	33.3±1.84	33.2	31.1	31.92±1.14
HbE (+A2) (%)	40.28±19.12	43.41±20.65	52.43±15.54	42.3±14.34	46.63±2.07	37.4	38.95±7.99	45.8	46.8	51.07±11.96
HbF (%)	46.31±23.82	45.08±12.47	31.9±23.46	51.4±14.6	47.4±6.67	53.5	54.75±0.92	15.9	35.8	45.17±11.68

Note: Data shown as mean±SD or number (%).

Abbreviations: Hb, hemoglobin; HbE (+A2), hemoglobin E with hemoglobin A2; HbF, fetal hemoglobin.; HCT, hematocrit; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin concentration; MCV, mean corpuscular volume; RBC, red blood cells

Figure 1 Comparison of height for age in beta-thalassemia patients.