Table 3. [Genetic Disorders of Interest in the Differential Diagnosis of Wiskott-Aldrich Syndrome]. - GeneReviews®

Gene	Disorder	MOI	Features of Disorder	Comment
WIPF1	Wiskott-Aldrich syndrome 2 (OMIM 614493)	AR	Recurrent infections, eczema, & thrombocytopenia Low numbers of B & T cells, defective T-cell proliferation & chemotaxis, low NK cell function, & abnormal WASP	Normal platelet volumes	WIPF1 molecular genetic testing should be considered in symptomatic males (esp those w/normal platelet volumes or in whom sequence analysis of WAS did not identify a pathogenic variant) & in symptomatic females.
ADA AK2 CD247 (CD3Z) CD3D CD3E CORO1A DCLRE1C IL7R PTPRC JAK3 LAT LCP2 LIG4 NHEJ1 PRKDC RAG1 RAG2	AR severe combined immunodeficiency ¹	AR	Recurrent infection, T- & B-cell dysfunction, & T-cell lymphopenia	Variable other clinical features ¹	Consider In males who initially present w/Pneumocystis carinii pneumonia. Note: Persistent thrombocytopenia is rarely, if ever, seen in these conditions.
CD40L	X-linked hyper IgM syndrome	XL	Recurrent infections, neutropenia, thrombocytopenia, & hemolytic anemia Dysfunction of B cells & defective T-cell activation (normal to low T-cell counts) Risk for lymphomas & other malignancies	IgM normal or high Serum IgG, IgA, & IgE severely deficient Gastrointestinal complications & neurologic deterioration
IL2RG	X-linked severe combined immunodeficiency (X-SCID)	XL	Severe & persistent infections, diarrhea, & poor growth T-B+NK-, nonfunctional B lymphocytes, & lymphocytopenia	Agammaglobulinemia (gamma chain deficiency), atrophy of thymus

Gene

Disorder

MOI

Features of Disorder

Comment

Overlapping w/Wiskott-Aldrich syndrome

Distinguishing from Wiskott-Aldrich syndrome

WIPF1

Wiskott-Aldrich syndrome 2 (OMIM 614493)

Recurrent infections, eczema, & thrombocytopenia
Low numbers of B & T cells, defective T-cell proliferation & chemotaxis, low NK cell function, & abnormal WASP

Normal platelet volumes

WIPF1 molecular genetic testing should be considered in symptomatic males (esp those w/normal platelet volumes or in whom sequence analysis of WAS did not identify a pathogenic variant) & in symptomatic females.

ADA
AK2
CD247 (CD3Z)
CD3D
CD3E
CORO1A
DCLRE1C
IL7R PTPRC
JAK3
LAT
LCP2
LIG4
NHEJ1
PRKDC
RAG1
RAG2

AR severe combined immunodeficiency ¹

Recurrent infection, T- & B-cell dysfunction, & T-cell lymphopenia

Variable other clinical features ¹

Consider In males who initially present w/Pneumocystis carinii pneumonia.
Note: Persistent thrombocytopenia is rarely, if ever, seen in these conditions.

CD40L

X-linked hyper IgM syndrome

Recurrent infections, neutropenia, thrombocytopenia, & hemolytic anemia
Dysfunction of B cells & defective T-cell activation (normal to low T-cell counts)
Risk for lymphomas & other malignancies

IgM normal or high
Serum IgG, IgA, & IgE severely deficient
Gastrointestinal complications & neurologic deterioration

IL2RG

X-linked severe combined immunodeficiency (X-SCID)

Severe & persistent infections, diarrhea, & poor growth
T-B+NK-, nonfunctional B lymphocytes, & lymphocytopenia

Agammaglobulinemia (gamma chain deficiency), atrophy of thymus

From: WAS-Related Disorders

GeneReviews^® [Internet].

Adam MP, Feldman J, Mirzaa GM, et al., editors.

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