Table I. SCID subtypes and transplantation-related characteristics.

Phenotype/syndrome	Genetic defect	Characteristics related to transplantation
T−B−NK−	ADA deficiency	ERT or gene therapy (on a research study) might be available and considered if MRD transplants are not available for HCT.
		ERT should be held before nonconditioned transplantation.
		Fifty percent of patients have marked neurologic and cognitive abnormalities after transplantation or with ERT.5,6
		B-cell function is usually recovered after unconditioned MRD transplantation.7
T−B−NK+	RAG1 or RAG2 mutation	There is increased risk of nonengraftment and graft rejection in nonconditioned mismatched HCT.3,4 No radiation sensitivity is present.
		B-cell function recovers in a minority (17%) of nonconditioned patients.3 There is a frequent need for boost transplants in nonconditioned HCT (83%).3
	Artemis deficiency (DCLRE1C)	DNA repair defects are seen (alkylating agents and radiation sensitivity).
		There are frequent late effects after transplantation with alkylating agents.2 Reconstitution of B-cell function is rare (<20%) in patients receiving MSD transplants without myeloablation.1
	Ligase IV deficiency	A DNA repair defect is seen.
		There are limited transplantation data.
T−B+NK−	Common γc (IL-2Rγ, X-linked SCID)	There are no barriers to engraftment, even with mismatched donors.3,4 Gene therapy is successful in correcting immune deficiency, but there is a high risk of malignant transformation in an early gene-therapy study.8
		Reconstitution of B-cell function develops in 30% to 40% of patients after nonconditioned transplantation with MMRD transplants.3,4 There are few long-term problems except for cutaneous warts.2
	Jak3	There are no barriers to engraftment.
		There is reconstitution of B-cell function in up to 50% of nonconditioned patients with MMRD transplants.3 Warts are seen late after transplantation.2
T−B+NK+/−	CD45 deficiency	Limited data are available.
T−B+NK+	IL-7Rα	There are good long-term outcomes and chance of B-cell function recovery without conditioning (70%).3
T−B+NK+	CD3γ, CD3δ, CD3ε, CD3ζ	Limited data are available. The degree of immunodeficiency and need for transplantation depend on specific mutation.
ZAP-70 deficiency	ZAP-70	CD8− lymphopenia and high IgE levels are seen.
		A case report indicates that conditioning might not be needed in closely matched transplants.9
Omenn syndrome	Hypomorphic RAG1, RAG2, or other SCID mutations	Autoreactive T cells causing inflammatory and allergic symptoms are found.
		Conditioning was historically used even with MRD transplants, although there are no data to suggest that it should be treated differently than the underlying genetic defect.
Reticular dysgenesis AK2 deficiency	Defective maturation of lymphoid and myeloid cells (stem cell defect) defect in mitochondrial adenylate kinase 2	Limited transplantation data are available. Full myeloablative conditioning might be needed before mismatched transplantation.10

ERT, Enzyme replacement therapy; ZAP-70, ζ chain–associated protein of 70 kDa.