From Agammaglobulinemia to Neutropenia: The TCF-3 Has Different Clinical Presentations

Agammaglobulinemia is caused by genetic disorders affecting B cell development and is assumed to be autosomal recessive in up to 15%. Autosomal recessive agammaglobulinemia (ARA) is a condition that causes immunodeficiency, and it can lead to severe complications such as otitis, sinusitis, and pneumonia. Genetic mutations include μ heavy chain, λ5, Igα, Igβ, BLNK, PIK3R1, and TCF3. There are several genes, including μ heavy chain, λ5, Igα, Igβ, BLNK, PIK3R1, and TCF3, that have been associated with ARA. TCF-3 is responsible for the development of T and B cells. This report describes four cases, one of which was agammaglobulinemia, followed by two cases of Immunoglobulin (Ig) subgroup deficiency, one of neutropenia, and one of hypogammaglobulinemia.

This report expands the spectrum of TCF3 deficiency types and highlights the crucial role of this transcription factor in B-lymphocyte differentiation.

Table 1.

The clinical and immunologic parameters of the patients.

	Patient1	Patient2	Patient3	Patient4
Age/ gender	8/M	3/M	5/M	26/M
Clinical findings	Recurrent bronchiolitis	Enterovirus encephalitis	Recurrent upper respiratory tract infections, peritonsillar abscess	Recurrent otitis media and pneumonia, hearing loss
		Facial dsymorfism
	Failure to thrive
Diagnosis at admission	THI	Agammaglobulinemia	Neutropenia	Ig subgroup deficiency
Current diagnosis	Ig subgroup deficiency	Agammaglobulinemia	Hypogammaglobulinemia	Ig subgroup deficiency
Mutation	TCF- 3 p.Pro177Leu (c.530C>T) heterozygous	TCF-3 p.Ala161Val (c.482C>T) heterozygous	TCF-3 C.1939C>A p.(pro647Thr) heterozygous	TCF-3 c.1813+8C>T (rs993094051) heterozygous
Immunologic parameters
ANS × 109cells/L	3240	5660	62	3290
ALS× 109cells/L	3780	2010	2850	2730
IgG(mg/dl)	304	145<	924	690
IgA(mg/dl)	81	6.7<	33	110
IgM(mg/dl)	105	18<	113	113
Ig Subgroups (mg/dl)	IgG1:238	N/A	N/A	IgG1 483
	IgG2:255			IgG2 166
	IgG3:16.7			IgG3 36.7
CD3 × 109cells/L	2683	1440	1995	1701
CD4 × 109cells/L	1738	274	769	1107
CD8 × 109cells/L	793	1080	1254	459
CD19 × 109cells/L	756	44	133	351
CD3-CD16CD56+NK cells × 109cells/L	185	880	684	459
Switched memory BCD19-IGgM-IgD+CD27 × 109cells/L	18.9	0	28	21.6
Vaccine response	positive	positive	positive	positive

	Patient1	Patient2	Patient3	Patient4
Age/ gender	8/M	3/M	5/M	26/M
Clinical findings	Recurrent bronchiolitis	Enterovirus encephalitis	Recurrent upper respiratory tract infections, peritonsillar abscess	Recurrent otitis media and pneumonia, hearing loss
		Facial dsymorfism
	Failure to thrive
Diagnosis at admission	THI	Agammaglobulinemia	Neutropenia	Ig subgroup deficiency
Current diagnosis	Ig subgroup deficiency	Agammaglobulinemia	Hypogammaglobulinemia	Ig subgroup deficiency
Mutation	TCF- 3 p.Pro177Leu (c.530C>T) heterozygous	TCF-3 p.Ala161Val (c.482C>T) heterozygous	TCF-3 C.1939C>A p.(pro647Thr) heterozygous	TCF-3 c.1813+8C>T (rs993094051) heterozygous
Immunologic parameters
ANS × 109cells/L	3240	5660	62	3290
ALS× 109cells/L	3780	2010	2850	2730
IgG(mg/dl)	304	145<	924	690
IgA(mg/dl)	81	6.7<	33	110
IgM(mg/dl)	105	18<	113	113
Ig Subgroups (mg/dl)	IgG1:238	N/A	N/A	IgG1 483
	IgG2:255			IgG2 166
	IgG3:16.7			IgG3 36.7
CD3 × 109cells/L	2683	1440	1995	1701
CD4 × 109cells/L	1738	274	769	1107
CD8 × 109cells/L	793	1080	1254	459
CD19 × 109cells/L	756	44	133	351
CD3-CD16CD56+NK cells × 109cells/L	185	880	684	459
Switched memory BCD19-IGgM-IgD+CD27 × 109cells/L	18.9	0	28	21.6
Vaccine response	positive	positive	positive	positive

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