J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website http://www.jocmr.org

Original Article

Volume 8, Number 5, May 2016, pages 379-384

Recombinase Activating Gene 1 Deficiencies Without Omenn Syndrome May Also Present With Eosinophilia and Bone Marrow Fibrosis

**Table 1.** Demographic and Clinical Findings of Patients With RAG1 Deficiency
SCID phenotype	n	Gender (f/m)	Mean age (months)	Mean age onset of symptoms (months)	Mean age diagnosis (months)	Consanguinity, n (%)	Autoimmunity, n (%)	CMV infection, n (%)	EBV infection, n (%)	BCG infection, n (%)
T⁺B^-NK⁺	2	1/1	27	4.1 ± 5.6 (0 - 8)	11.1 ± 1.4 (10 - 12)	0	0	1 (50%)	0	1 (12.5%) (BCG abscess)
T⁺B⁺NK⁺	8	3/5	118 ± 85	10.2 ± 11.1 (2 - 36)	67.2 ± 80.8 (12 - 244)	5 (62.%)	3 (37%)	5 (62%)	3 (37.5%)	0
T^-B^-NK⁺	8	5/3	57 ± 40	0.4 ± 0.9 (0 - 2.5)	5.8 ± 3.1 (2 - 11)	6 (75%)	2 (25%)	3 (37.5%)	1 (12.5%)	2 (25%) (BCGitis)
Omenn	3	1/2	-	0.2 ± 0.2 (0 - 5)	1.8 ± 0.7 (1 - 2.5)	0	1 (33%)	1 (37.5%)	0	0
Total	21	10/11	87 ± 73	4.4 ± 8.2	29 ± 56	11 (52%)	6 (28%)	10 (47.6%)	4 (19%)	3 (14%)

Table 1. Demographic and Clinical Findings of Patients With RAG1 Deficiency

SCID phenotype

Gender (f/m)

Mean age (months)

Mean age onset of symptoms (months)

Mean age diagnosis (months)

Consanguinity, n (%)

Autoimmunity, n (%)

CMV infection, n (%)

EBV infection, n (%)

BCG infection, n (%)

T⁺B^-NK⁺

1/1

4.1 ± 5.6 (0 - 8)

11.1 ± 1.4 (10 - 12)

1 (50%)

1 (12.5%) (BCG abscess)

T⁺B⁺NK⁺

3/5

118 ± 85

10.2 ± 11.1 (2 - 36)

67.2 ± 80.8 (12 - 244)

5 (62.%)

3 (37%)

5 (62%)

3 (37.5%)

T^-B^-NK⁺

5/3

57 ± 40

0.4 ± 0.9 (0 - 2.5)

5.8 ± 3.1 (2 - 11)

6 (75%)

2 (25%)

3 (37.5%)

1 (12.5%)

2 (25%) (BCGitis)

Omenn

1/2

0.2 ± 0.2 (0 - 5)

1.8 ± 0.7 (1 - 2.5)

1 (33%)

1 (37.5%)

Total

10/11

87 ± 73

4.4 ± 8.2

29 ± 56

11 (52%)

6 (28%)

10 (47.6%)

4 (19%)

3 (14%)

**Table 2.** Clinical Findings of Patients With RAG1 Deficiency
SCID phenotype	n	Failure to thrive, n (%)	Chronic lung diseases (n)	Organomegaly, n (%)	Erythroderma, n (%)	Bone marrow fibrosis, n (%)
T⁺B^-NK⁺	2	2 (100%)	Small airway disease: 1	1 (50%)	0	1 (50%)
T⁺B⁺NK⁺	8	3 (37.5%)	Bronchiectasis: 5 Small airway disease: 3	5 (62.5%)	1 (12.5%)	1 (12.5%)
T^-B^-NK⁺	8	4 (50%)	Bronchiectasis: 1	3 (37.5%)	0	0
Omenn	3	3 (100%)	0	2 (66.7%)	3 (100%)	1 (33.3%)
Total	21	12 (57%)	10	11 (52.3%)	4 (19%)	3 (14%)

Table 2. Clinical Findings of Patients With RAG1 Deficiency

SCID phenotype

Failure to thrive, n (%)

Chronic lung diseases (n)

Organomegaly, n (%)

Erythroderma, n (%)

Bone marrow fibrosis, n (%)

T⁺B^-NK⁺

2 (100%)

Small airway disease: 1

1 (50%)

T⁺B⁺NK⁺

3 (37.5%)

Bronchiectasis: 5
Small airway disease: 3

5 (62.5%)

1 (12.5%)

T^-B^-NK⁺

4 (50%)

Bronchiectasis: 1

3 (37.5%)

Omenn

3 (100%)

2 (66.7%)

3 (100%)

1 (33.3%)

Total

12 (57%)

11 (52.3%)

4 (19%)

3 (14%)

**Table 3.** Hematologic Evaluation of Patients With RAG1 Deficiency
SCID phenotype	n	Neutropenia, n (%)	Lymphopenia, n (%)	Anemia, n (%)	Thrombocytopenia, n (%)	Eosinophilia, n (%)
T⁺B^-NK⁺	2	1 (50%)	1 (25%)	2	2 (100%)	0
T⁺B⁺NK⁺	8	1 (12.5%)	1 (12.5%)	8	1 (12.5%)	2 (25%)
T^-B^-NK⁺	8	2 (25%)	4 (50%)	8	0	5 (62.5%)
Omenn	3	1 (33%)	0	3	1 (33%)	3 (100%)
Total	21	5 (23%)	6 (28%)	21	4 (19%)	10 (47%)

Table 3. Hematologic Evaluation of Patients With RAG1 Deficiency

SCID phenotype

Neutropenia, n (%)

Lymphopenia, n (%)

Anemia, n (%)

Thrombocytopenia, n (%)

Eosinophilia, n (%)

T⁺B^-NK⁺

1 (50%)

1 (25%)

2 (100%)

T⁺B⁺NK⁺

1 (12.5%)

2 (25%)

T^-B^-NK⁺

2 (25%)

4 (50%)

5 (62.5%)

Omenn

1 (33%)

3 (100%)

Total

5 (23%)

6 (28%)

4 (19%)

10 (47%)

**Table 4.** Lymphocyte Subsets of Patients With RAG 1 Deficiency
SCID phenotype	CD3 (%)	CD19 (%)	CD4 (%)	CD8 (%)	NK (%)	HLA-DR (%)	HLA-DR elevation (n)	γδ elevation (n)	CD45RA (%)	CD45RO (%)
T⁺B^-NK⁺ (n = 2)	55 ± 6	5.1 ± 5.2	6.1 ± 4.2	42 ± 4.1	42 ± 8.4	34 ± 3.5	2	1	0.6 ± 0.03	5.6 ± 2.2
T⁺B⁺NK⁺ (n = 8)	69 ± 20	4.5 ± 5	36 ± 24	32 ± 16	20 ± 22	27 ± 20	3	3	32 ± 24	49 ± 20
T^-B^-NK⁺ (n = 8)	7.5 ± 14	7.6 ± 21	4.6 ± 8.1	3.4 ± 5.1	86 ± 8.4	2.7 ± 4.2	0	0	29 ± 20	39 ± 30
Omenn (n = 3)	83 ± 6	0.19 ± 0.18	44 ± 28	34 ± 25	12 ± 6	66 ± 6	3	0	-	-
Total	46 ± 35	5.6 ± 13	22 ± 24	22 ± 20	42 ± 36	24 ± 25	8	4	35 ± 26	28 ± 30

Table 4. Lymphocyte Subsets of Patients With RAG 1 Deficiency

SCID phenotype

CD3 (%)

CD19 (%)

CD4 (%)

CD8 (%)

NK (%)

HLA-DR (%)

HLA-DR elevation (n)

γδ elevation (n)

CD45RA (%)

CD45RO (%)

T⁺B^-NK⁺ (n = 2)

55 ± 6

5.1 ± 5.2

6.1 ± 4.2

42 ± 4.1

42 ± 8.4

34 ± 3.5

0.6 ± 0.03

5.6 ± 2.2

T⁺B⁺NK⁺ (n = 8)

69 ± 20

4.5 ± 5

36 ± 24

32 ± 16

20 ± 22

27 ± 20

32 ± 24

49 ± 20

T^-B^-NK⁺ (n = 8)

7.5 ± 14

7.6 ± 21

4.6 ± 8.1

3.4 ± 5.1

86 ± 8.4

2.7 ± 4.2

29 ± 20

39 ± 30

Omenn (n = 3)

83 ± 6

0.19 ± 0.18

44 ± 28

34 ± 25

12 ± 6

66 ± 6

Total

46 ± 35

5.6 ± 13

22 ± 24

22 ± 20

42 ± 36

24 ± 25

35 ± 26

28 ± 30

**Table 5.** RAG1 Mutations and Clinical Outcomes of Patients
SCID phenotype	RAG1 mutation	HSCT, n	Donor	Exitus	n
T⁺B^-NK⁺	p.R561H homozygous	1	Unrelated donor	0	2
H249R/K820R compound heterozygous	1	Unrelated donor	0
T⁺B⁺NK⁺	H249R/K820R compound heterozygous: 4	1	Sister	1	8
H249R heterozygous: 2	1	Mother	0
H249R homozygous: 1	0	0	1
delAA368-369 homozygous: 1	1	Mother	1
T^-B^-NK⁺	H249R/K820R compound heterozygous: 2	0	0	2	8
H249R homozygous: 2	1	Unrelated donor	0
Leu846Pr homozygous: 1	1	Brother	0
R394Q homozygous: 2	1	Father	2
p.R776Q del 3047-49 GCC: 1	0	0	1
Omenn	H249R heterozygous: 2	1	Unrelated donor	2	3
arg108x/his249arg/leu797val/lys820arg heterozygous: 1	0		1
Total		9	9	11	21

Table 5. RAG1 Mutations and Clinical Outcomes of Patients

SCID phenotype

RAG1 mutation

HSCT, n

Donor

Exitus

T⁺B^-NK⁺

p.R561H homozygous

Unrelated donor

H249R/K820R compound heterozygous

Unrelated donor

T⁺B⁺NK⁺

H249R/K820R compound heterozygous: 4

Sister

H249R heterozygous: 2

Mother

H249R homozygous: 1

delAA368-369 homozygous: 1

Mother

T^-B^-NK⁺

H249R/K820R compound heterozygous: 2

H249R homozygous: 2

Unrelated donor

Leu846Pr homozygous: 1

Brother

R394Q homozygous: 2

Father

p.R776Q del 3047-49 GCC: 1

Omenn

H249R heterozygous: 2

Unrelated donor

arg108x/his249arg/leu797val/lys820arg heterozygous: 1

Total