Table 4. Conditions with low or absent TRECs and clinically significant T lymphocytopenia (<1,500 T cells/uL).

I. Typical SCID (see genotypes in Table 2), defined as <300 autologous T cells/uL and <10% of normal proliferation to the mitogen PHA.

II. Leaky SCID, due to incomplete (hypomorphic) mutation(s) in a typical SCID gene, with 300–1,500 T cells/uL and impaired, but not absent (10–30% of normal) proliferation to PHA.

III. Variant SCID, with no defect in a known SCID gene and 300–1,500 T cells/uL that demonstrate impaired function.

IV. Syndromes with variably affected cellular immunity that may be severe:

Complete DiGeorge syndrome*

Partial DiGeorge syndrome with low T lymphocytes*

CHARGE syndrome*

Jacobsen syndrome*

Trisomy 21*

RAC2 dominant interfering mutation*

DOCK8 deficient hyper-IgE syndrome**

Cartilage hair hypoplasia

V. Secondary T lymphocytopenia:

Neonatal cardiac surgery with thymectomy*

Neonatal leukemia*

Gastroschesis*

Third spacing*

Extreme prematurity (resolves to normal with time)*

Possibly severe prenatal HIV disease (hypothesized, but not observed to date)

^*, observed to have low or absent TRECs upon newborn screening in one or more cases to date in US pilot programs or published reports.

^**observed to have low or absent TRECs in one or more cases after diagnosis; newborn samples not available.