CLINICAL AND EPIDEMIOLOGIC STUDIES OF FAMILIAL HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS IN JAPAN

Background and Procedure. The etiology of familial hemophagocytic lymp hohistiocytosis (FHL), which is characterized by fever, hepatosplenome galy, pancytopenia, and coagulopathy, remains unknown. We analyzed 43 FHL patients, all with affected siblings, in 18 families who were iden tified during the period 1986-1995 in Japan. Results. The presence of consanguinity was evident in two families (11%). The majority of famil ies lived in western Japan, where the frequency of consanguineous marr iage is high. The incidence of FHL was significantly higher in the wes tern island, Kyushu, than in other areas. The segregation ratio calcul ated for these families was 0.35 by the Weinberg proband method, showi ng the autosomal-recessive inheritance of the disease. Since the diagn osis of an FHL patient without affected siblings (sporadic case) is qu ite difficult, we calculated the possible number of sporadic cases; ap proximately 122 patients could be identified as sporadic FHL cases dur ing the same period in Japan. Most of the clinical and laboratory find ings were not distinguishable from those of other types of lymphohisti ocytosis. However, atypical lymphoid cells with azurophilic granules i n peripheral blood were observed in half of the patients at diagnosis, suggesting the clinical importance of this parameter for early diagno sis. Despite intensive therapy, the prognosis of FHL was extremely poo r; but 4 of the 8 patients who have survived had received bone marrow transplantation (BMT), indicating the effectiveness of BMT for this di sorder. Conclusions. The distribution of FHL in areas of highly freque nt consanguineous marriage and the segregation analysis indicated a ge netic factor in FHL. The identification of the genes for FHL is expect ed to contribute to a cure for this disorder, and might also enable FH L carrier detection and donor selection for BMT. (C) 1998 Wiley-Liss, Inc.