Severe combined immune system deficiency
Severe combined immune system deficiency is the name given to a group of hereditary
diseases that mainly affect the immune system. In this group of diseases there is
a lack of 2 major types of immune response cells:
- B cells - these are responsible for the secretion of antibodies (materials called
immunoglobulins, which recognize bacteria and other infectious organisms). This
type of immunity is called humoral immunity.
- T cells - these recognize and treat infectious organisms. This type of immunity
is called cellular immunity.
In severe combined immune system deficiency both the T-cells and B-cells are deficient,
and as a result the patient will suffer from life-threatening severe infections.
Life expectancy is markedly decreased (infancy or childhood).
There are several types of severe combined immune system deficiency:
There is a uniquely high frequency of severe combined immune system deficiency (SCID)
associated with deficiency of both T-cell and B-cell immunity among Athabaskan-speaking
Native Americans -this form of the disorder is termed SCIDA. It has been reported
in the Navajo and Apache tribes and among the Dene Indians, a small tribe of Athabascan
speakers living in the Northwest Territories of Canada.
- Some are part of a syndrome that affects other organs (for example Omenn syndrome).
- Some are transmitted by
autosomal recessive inheritance (for example Adenosine deaminase deficiency,
SCID, which is common among Athabaskan-speaking Native Americans, etc.)
- Some are transmitted by
The incidence of SCIDA is said to be approximately 1 in 2,000 live births among
Navajo Indians. Clinically, affected children present with oral/genital ulcers and
life-threatening infections within the first 3 months of life. Without a bone marrow
transplant, most die by 6 months of age.
- Some are part of a syndrome such as Omenn syndrome, Adenosine deaminase deficiency,
and SCID - these are transmitted by autosomal recessive inheritance,which means
that when both parents are carriers, the child will only be affected if he or she
inherits two abnormal genes - one from the mother and one from the father.
- Some cases of SCID are transmitted by
X-linked inheritance - in these conditions only males are affected.
As described above, the disease is relatively frequent among Navajo and Apache Native
Americans. In these groups the carrier rate is 1:20 among individuals with no family
Associated features that can be demonstrated in tests performed during pregnancy
In most types of SCID there are no definitive signs that are detectable during the
pregnancy, and only DNA tests can confirm the diagnosis.
In all these cases it is important to refer the couple for genetic counseling, to which they should bring
all data, including the results of other tests performed during the pregnancy such
as alpha-fetoprotein, nuchal translucency, etc.
What is the risk of recurrence in a subsequent pregnancy?
In SCIDA, the type that is common among the Navajo and Apache peoples, and in the
other SCIDs that are transmitted by autosomal recessive inheritance:
In the type of SCID that is transmitted by
- For a couple who has already had an affected child, the risk is 25% in every subsequent
pregnancy. When only one parent carries the abnormal gene, there is no risk that
any of their offspring will have the disease; however, in such families there is
a 50% chance that the infant will be a carrier, but he himself will be healthy,
like the carrier parent.
- The risk for more distant relatives depends on the degree of relationship between
the relatives and the affected individuals, the ethnic groups of their partners,
affected relatives of partners, consanguinity
between the parents, if present, etc., and is established within genetic counseling.
- For a couple who has already had an affected child, the risk is 50% in every subsequent
pregnancy with a male fetus.
- The risk for more distant relatives on the maternal side depends on the degree of
relationship between the relatives and the affected individuals, and is established
within genetic counseling. Carrier females can be identified by genetic tests.
Immune System - Natural Killer Cell
Molecular genetic information
The gene for the disease
In SCIDA (the type that is common among the Navajo and Apache peoples): the DCLRE1C
gene, which produces the Artemis protein and is situated on chromosome 10p.
Among the Navajo and Apache peoples, a direct test can be performed to identify
the mutation in the gene by testing for the common mutations. See: Testing the disease-causing
gene for mutations that are common in a specific ethnic group - autosomal recessive
In the other types, testing of other genes that may be involved is required.
The mutation Y192TER (C-to-A transversion in exon 8 of the DCLRE1C gene) is the
one that is common in the Navajo and Apache peoples. The carrier rate varies between
1:10 in healthy individuals of Navajo and Apache origin to 1:100 in other ethnic
groups. In other ethnic groups, carriers cannot be identified.
In view of this, it is very important to ascertain the ethnic origins of the couple,
and it is advisable to examine (carrier DNA testing) those couples where both partners
are fully or even partially of Navajo or Apache origin.
See also: Introduction to population DNA screening for
autosomal recessive diseases such as Cystic fibrosis and others.
Carrier status testing in relatives of patients with severe combined immune system
It is important that relatives of patients with severe combined immune system deficiency
clarify which mutations are present in the patient or parents in their family in
order to ascertain that they are included in the battery of mutations routinely
tested for - otherwise it will be necessary to expand the list of mutations tested
for and/or examine the partner. This will be discussed in genetic counseling.
Same as the diagnostic test.
Prenatal diagnosis can also be offered to each couple who has had an affected child.
The best way is after identifying the mutations in the parents, but if these are
not found, indirect linkage analysis can be performed. See:
Indirect testing for genetic markers in a family that has one or more patients -
when there is only one gene that can cause the disease - autosomal recessive diseases.
Preimplantation diagnosis (before the embryonic
cells implant in the uterine wall) can also be offered for this disease - this is
performed in special centers, and in special cases this can be considered within