DGM (Dutch-German Mennonite)

Inheritance: autosomal recessive
Genes: c9q21.3-22

HLH1
FLHL1
HPLH1
Familial hemophagocytic reticulosis
Erythrophagocytic lymphohistiocytosis

Fever
Cytopenia
Hepatosplenomegaly
Lymphadenopathy
Hemolytic anemia

Hemophagocytic Lymphohistocytosis 1

Clinical Characteristics

General description (for patients):  

FLHL is disorder of abnormal cells infusing into tissues and replacing normal cells.  Organs involved are usually the liver, spleen, brain, bone marrow, and lymph glands.  As a result, these organs are unable to function normally and often become enlarged.  Anemia and low white counts are typical.  As a result, infections are a constant threat.  When the brain and its covers are involved, high fevers may result.  Untreated individuals may die in infancy.

Medical description: 

Infiltration of tissues with histiocytes seems to be the basis for the clinical manifestations of this disease.  Bone marrow, meninges, liver, and lymph glands are the most commonly involved sites resulting in anemia, low white counts, thrombocytopenia, hepatosplenomegaly, lymphadenopathy and high fever.  The histiocytoses of various types seem to form a spectrum of disease but this specific type (FLH1) has been found in an inbred Canadian Mennonite population in which the clinical picture was more consistent.  Infants presented by about three months of age with hepatomegaly and lymphadenopathy.  Untreated cases died in infancy but even those treated with prednisone and cytotoxic agents succumbed with high fever and hemolytic anemia with a blood profile suggestive of leukemia.  Susceptibility to infection is a problem.

Genetics:

Familial hemophagocytic lymphohistiocytosis seems to be an autosomal recessive disorder as suggested by examples of offspring from consanguineous matings.  Several inbred families have been demonstrated to have linkage to a region on chromosome 9 (9q21.3-q22). This disorder has been found in a large inbred Canadian Mennonite kindred but the genotype is unknown.

Treatment:

Prednisone and cytotoxic drugs may have temporary benefit in some patients but remission is possible only with allogeneic bone marrow transplantations from HLA-identical family members.

Prognosis:

Generally poor, but intensive treatment can lead to remission.

Ancillary treatments and support: 

Protection from infection, treatment of anemia.

Specialists and specialty centers:

Hematologist, pediatrician, neurologist.

References:

Cutbush, W., De Veber, L.L., and Rathbun, J.C.:  Familial histiocytosis. (Abstract) Canad. Res. Soc. Meeting, St. John’s Newfoundland, 1974.

Janka, G.E., and Schneider, E.M.:  Modern management of children with haemmophagocytic lymphohistiocytosis.  Brit. J. Haemat. 124: 4-14, 2004.  PubMed ID: 14675403

Resources:

Histiocytosis Association of America