APA (Old Order Amish; Eastern Pennsylvania)
DGM (Dutch-German Mennonite)

Inheritance: autosomal recessive
Genes: CD3D

SCID
T cell negative
B cell negative
NK cell positive

Immunodeficiency
Hepatomegaly
Splenomegaly
Pancytopenia
Infections

Severe Combined Immunodeficiency (CD3D)

Clinical Characteristics

General description (for patients):

This is one of several inherited disorders of the immune system that increase susceptibility to infections in plain people.  These are sometimes referred to as SCIDs (severe combined immunodeficiency).  Signs and symptoms of infection appear shortly after birth, most commonly causing breathing difficulties and/or diarrhea.  Resistance to viral, bacterial and fungal infections is greatly reduced.  Untreated, most infants die within a few months but bone marrow transplantation can restore resistance to such infections.

Medical description: 

This is one of several heritable disorders of the immune system that usually result in severe, disseminated and often fatal infections during the first few months of life.  Pathogens can be isolated from stool, urine, and respiratory secretions.  Hypotension, hepatomegaly, liver failure and respiratory arrest are common.   The thymus may be normal in this disease.  Infants are susceptible to cytomegalovirus, bacteria, and even weakly pathogenic adenoviruses.  The only known treatment is bone marrow transplantation which can restore normal immunity.

Genetics:

A number of mutations can cause this form of immunodeficiency.  Three affected sibs in Dutch-German Mennonites have been reported to have homozygosity of a nonsense mutation (202C>T) in the CD3D gene located on chromosome 11 (11q23).  The parents were heterozygous for the mutation, consistent with autosomal recessive inheritance.  This condition resulting from the same mutation also occurs among plain people in Eastern Pennsylvania.

Treatment:

Urgent treatment of infections is important but the only long-term effective treatment is a bone marrow transplant.

Prognosis:

Uniformly fatal in the absence of a bone marrow transplant.

Ancillary treatments and support:

Vigilant treatment of infections with nutritional supplementation.

Specialists and specialty centers:

Pediatrician, immunologist, nutritionist, infectious disease

References:

Dadi, H.K., Simon, A.H., and Roifman, C.M.:  Effect of CD3-delta deficiency on maturation of alpha/beta and gamma/delta T-cell lineages in severe combined immunodeficiency. New Eng. J. Med. 349: 1821-1828, 2003.  PubMed ID : 14602880

De Saint Basile, G., Geissmann, F., Flori, E., Uring-Lambert, B., Soudais, C., Cavazzana-Calvo, M., Durandy, A., Jabado, N., Fischer, A., and Le Diest, F.:  Severe combined immunodeficiency caused by deficiency in either the delta or the epsilon subunit of CD3.  J. Clin. Invest. 114: 1512-1517, 2004.  PubMed ID: 15546002

Resources:

Immune Deficiency Foundation