History and exam
Key diagnostic factors
common
at-risk demographic
family history of SCID, infant death, or consanguinity
Family history of a known SCID, or a history of siblings who died from infection at <2 years of age, should alert the physician to the possibility of SCID or another underlying primary immunodeficiency.
X-linked SCID should be suspected if there is a family history of male deaths in infancy. A history of consanguinity should heighten the suspicion of genetic diseases with autosomal-recessive inheritance (i.e., all forms of SCID, except X-linked SCID).
recurrent and unusually severe infections
Patients with SCID often present with recurrent and unusually severe bacterial, viral, and fungal infections early in life.
Infections with opportunistic pathogens, such as Pneumocystis jirovecii, should alert the clinician to the possibility of SCID.[8][23]
Serious infections with viruses such as respiratory syncytial virus, adenovirus, Epstein-Barr virus, cytomegalovirus, and parainfluenza can be associated with SCID.[8][23]
Findings indicative of infection, such as tachypnea, rales, oral thrush, and fungal infections of the skin or nails may be noted. Severe and intractable oral thrush is common in SCID.[31]
chronic diarrhea
This often occurs in patients with SCID secondary to persistent viral gastroenteritis. Common viruses include adenovirus, cytomegalovirus, and rotavirus.[31] The live rotavirus vaccine should not be given to patients suspected or known to have SCID.
failure to thrive
absent lymphoid tissue
An absence of tonsils and lymph nodes may be noted, but can be difficult to detect in young infants.[15]
Other diagnostic factors
uncommon
rash
In patients with hypomorphic variants of SCID, a diffuse erythrodermal rash can develop in the first month of life.[34]
A similar cutaneous presentation (along with hepatosplenomegaly and eosinophilia) can be seen in SCID patients with maternal T-cell engraftment occurring in utero (i.e., a sign of graft-versus-host disease), and transfusion with non-irradiated blood products.[31]
Presence of erythroderma or rash also suggests the possibility of a differential diagnosis of Omenn syndrome, a clinical diagnosis associated with several SCID-associated genetic defects.[4]
oral or genital ulcers
Patients with Artemis/DNA cross-link repair 1C (DCLRE1C) SCID can have associated oral or genital ulcers.[32]
microcephaly
Patients with DNA ligase IV deficiency can have associated microcephaly.[33]
skeletal abnormalities
Patients with adenosine deaminase deficiency can have associated skeletal abnormalities.[23]
blindness
Patients with adenosine deaminase deficiency can have associated blindness.[23]
dystonia
Patients with adenosine deaminase deficiency can have associated dystonia.[23]
Risk factors
strong
Family history of SCID
SCID is a group of inherited genetic disorders. Most forms of SCID follow an autosomal-recessive inheritance pattern; however, the most common form of SCID (X-linked SCID) in populations with a low proportion of consanguineous families follows an X-linked recessive inheritance pattern.
Family history of SCID should alert the physician to the possibility of SCID.
Family history of infant death
A history of siblings who died from infection at <2 years of age should alert the physician to the possibility of SCID or another underlying primary immunodeficiency. This is particularly relevant if there is parental consanguinity.
If there is a family history of male deaths in infancy, X-linked SCID should be suspected.
Athabascan-speaking Native American people
Incidence of autosomal-recessive SCID caused by genetic mutations in the Artemis/DNA cross-link repair 1C (DCLRE1C) gene defect is high among Athabascan-speaking Native American people (approximately 52 per 100,000 live births).[15]
Consanguinity
A history of consanguinity should heighten the suspicion of genetic diseases with autosomal-recessive inheritance (i.e., all forms of SCID, except X-linked SCID).
The incidence of autosomal-recessive SCID is high in populations with high rates of parental consanguinity.[12][13][14] In Saudi Arabia, SCID incidence of 1 per 2,906 live births has been reported.[14]
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