DGM (Dutch-German Mennonite)

Inheritance: autosomal recessive
Genes: ZAP70

SCID
T cell negative
B cell negative
NK cell positive

Susceptibilty to infection
Lymphopenia
Thymic hypoplasia
Failure to thrive

Severe Combined Immunodeficiency (Swiss Type)

Clinical Characteristics

General description (for patients):

This disorder is one of several commonly called SCIDs (severe combined immunodeficiency).  The common feature is decreased resistance to infection of all types, usually with onset in early infancy.  The thymus in this disorder is usually small and maybe absent.  Lymphocytes, a type of white cell in the blood, are greatly reduced in number.  Any part of the body may be infected with diarrhea, bronchitis and pneumonitis, and bladder infections common.  Sometimes viral, bladder, and fungal infections are simultaneously present.  Most infants die in the first year of life unless they receive a bone marrow transplant.

Medical description:

This heritable disorder of the immune system is associated with lymphopenia and thymic hypoplasia.  Lymphopenia can be profound.  At one point it was called Swiss-type agammglobulinemia but today is recognized as a heterogeneous disorder.  Infants can be infected with a variety of pathogens, viral, bacterial and fungal, within weeks following birth and most die in the first year of life.  Bone marrow transplantation can be an effective treatment.

Genetics: 

This is an autosomal recessive disorder, perhaps more than one.  The disorder was reported in seven patients in five Dutch-German Mennonites families in 1967.  It has also been seen among plain people in the Midwest US. and in Eastern Pennsylvania.  A mutation (IVS4-11G>A) in the ZAP70 intron/exon transition region on chromosome 11 (11p13) seems to be responsible for the defect in immunity via a deficiency in ZAP70 kinase.

Treatment:

Immediate and vigorous treatment of infection is important but bone marrow transplantation is the only effective long-term treatment.

Prognosis:

Uniformly fatal in childhood in the absence of bone marrow transplantation.

Ancillary treatments and support:

Optimum nutrition, and medical monitoring

Specialists and specialty centers:

immunologist, pediatrician, infectious disease, nutritionist

References:

Haworth, J.C., Hoogstraten, J., Taylor, H.: Thymic alymphoplasia.  Arch. Dis. Child. 42: 40-54, 1967. PubMed ID: 6019467

Arpaia, E., Shahar, M., Dadi, H., Cohen, A., and Roifman, C.M.:  Defective T cell receptor signaling and CD8+ thymic selection in humans lacking zap-70 kinase. Cell 76: 947-958, 1994. PubMed ID: 8124727

Buckley, R. H.:  Molecular defects in human severe combined immunodeficiency and approaches to immune reconstitution.  Annu. Rev. Immun. 22: 625-655, 2004.  PubMed ID: 15032591

Resources:

Immune Deficiency Foundation