ALS and PDC of Guam: forty-year follow-up.

Background: It was noticed in the mid-1950s that the incidence of ALS and parkinsonism–dementia complex (PDC) were much higher on Guam than anywhere else in the world. In 1958, a registry of patients and controls was established to ascertain the familial and genetic aspects of these diseases. Patients and individually matched controls and their relatives were registered from 1958 to 1963. The registry was updated and analyzed in 1998 through 1999. Objective: To ascertain whether first-degree relatives of patients had a higher risk for developing ALS or PDC than relatives of controls. Methods: During the period of 1958 to 1963, 126 new patients and 126 individually matched controls and their respective first-degree relatives and spouses were evaluated neurologically and registered. Forty years later, the number of new cases among the patient and control relatives were compared to an expected number of new cases based on the age- and sex-specific incidence of ALS and PDC in the population at large. Results: From 1958 to 1999, there were 102 new ALS or PDC cases among relatives of patients and 33 among relatives of controls. These values were compared with the derived expected values. There were more observed than expected new cases among patients’ relatives, and less observed cases than expected among the controls’ relatives. Conclusions: Relatives of patients with ALS or PDC have significantly higher risks for developing the disease than the Guamanian population, whereas relatives of controls have significantly lower risks.