An X-linked Recessive ‘Malignant’ Reticuloendothelosis

In the last 2 generations of a Latin American family 17 males have died prior to 6 years of age. All were related in the family through their mothers. clinical information on 16 of the boys indicated that the illness was characterized by fever, pallor, jaundice, hepatosplenomegaly, and lymphadenopathy with the median age of onset of illness being 14 months (4–62 months) and the median duration of illness being 22 days (1–50 days). Histologic studies on 12 of the children revealed bone marrow plasmacytosis and a mononuclear cell infiltrate of the liver, spleen, and lymph nodes, and less frequently of the brain, kidney, heart, and lungs, consistent with a malignant reticuloendotheliosis.

The most recently affected child was found to have anemia, thrombocytopenia, elevated IgG, IgA and IgM, normal phytohemagglutinin stimulation, in vitro transformation of peripheral blood lymphocytes, and an abnormal karyotype.

All first-degree relatives of affected children have normal peripheral blood counts, karyotyping, delayed hypersensitivity and lymphocyte proliferation studies, normal to elevated IgG and IgM levels with normal IgA, and absence of in vitro transformation of peripheral blood lymphocytes.

This is the first reported instance of a familial maliganant reticuloendotheliosis occurring in a pattern consistent with an X-linked recessive mode of inheritance.