Screening for severe combined immunodeficiency in neonates

Figures & data

Table 1 Identified gene mutations in severe combined immunodeficiency defined by lymphocyte population

Lymphocyte population	Disease	Gene	% of cases
T−B+NK+	IL-7Rα chain	IL7RA	10
	CD3δ deficiency	CD3D
	CD3ɛ deficiency	CD3E
	CD3ζ deficiency	CD3Z
	CD45 deficiency	PTPRC
	ZAP70 deficiency	ZAP79
	CD25 deficiency	IL2RA
	Actin-regulating protein coronin 1A deficiency	CORO1A
T−B+NK−	Common γ chain deficiency	IL2RGa	50
	Janus kinase 3 deficiency	JAK3	6.5
T−B−NK+	Recombinase activating gene 1 deficiency	RAG1	3
	Recombinase activating gene 2 deficiency	RAG2	3
	Artemis deficiency	DCLRE1C
	DNA ligase IV deficiency	LIG4
	Cernunnos deficiency	NHEJ1
	DNA protein kinase catalytic subunit deficiency	PRKDC
T−B−BK−	Adenosine deaminase deficiency	ADA	15
	Purine nucleoside phosphorylase deficiency	PNP
	Reticular dysgenesis	AK2

Notes:

a X-linked disease. Data from^2,17,18.

Abbreviations: B, B-cell; IL, interleukin; NK, natural killer cell; T, T-cell.

Table 2 Wilson and Jungner criteria for population-based newborn screening

Incidence of disease merits newborn screening

Disease is not easily identified through physical examination

Disease must result in severe clinical manifestations

Prognosis improves with early diagnosis and treatment

Available, economic, sensitive, and specific screening test

Note: Data from³².

Table 3 Recommended infectious disease prophylaxis for newborns suspected of having SCID

Prophylaxis	Drug (dose)	Time of Initiation	Alternatives	Comments
In newborns
PCP	Oral TMP-SMX (5 mg TMP/kg once a day for 2 consecutive days weekly)	1 mo old	Oral atovaquone (30 mg/kg once a day)	Verify that bilirubin is <2 times the upper limit of normal before starting; monitor ALT and AST every 2–4 wk
HSV and VSV	Oral acyclovir (20 mg/kg per dose 3 times a day)	At first visit
RSV	Palivizumab (15 mg/kg administered intramuscularly)	1 mo old		Given during peak RSV season, typically November–March
General (bacterial/viral)	IVIG (0.4–0.5 g/kg every month)	1 mo old		Monitor troughs monthly and maintain immunoglobulin >600 mg/dL
Fungal	Fluconazole (6 mg/kg once daily)	1 mo old	Micafungin	Follow AST and ALT every 2–4 wk
In family members or close contacts
Influenza	Inactivated or attenuated influenza vaccine	Seasonally		Attenuated vaccine safe in family members of infant with SCID
Pertussis	Tdap vaccine	Per routine childhood vaccinations		One booster for adolescents (11–12 y old), adults 19–64 y old, and adults >65 y old

Note: Reprinted from The Journal of Allergy and Clinical Epidemiology, 129, James Verbsky, Monica Thakar, John Routes, The Wisconsin approach to newborn screening for severe combined immunodeficiency, 622–627, Copyright 2012, with permission from Elsevier.⁷

Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; HSV, herpes simplex virus; IVIG, intravenous immunoglobulin; mo,month; PCP, Pneumocystis carinii pneumonia; RSV, respiratory syncytial virus; SCID, severe combined immunodeficiency; TMP-SMX, trimethoprim-sulfamethoxazole; VSV, varicella stomatitis virus; wk,weeks; y, years.

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