(n the mid-1980s I made an early career mistake and qualified as a pharmacist. I did my pre-registration work at the -- now closed -- district hospital in Dewsbury, a Yorkshire town of roughly 60,000 people. Dewsbury is in a steep valley and the working-class population tended not to travel: according to an older relative who worked there all his life, he knew co-workers who had been born, worked, lived, and retired in Dewsbury without ever travelling more than ten miles away from their birthplace. (Automobiles didn't really become a mass-cultural phenomenon there until the 1950s-1960s.) Cue lots of first-cousin marriages. During the 1970s, a Pakistani immigrant community arrived ... also from an isolated mountain valley town that didn't have much time for exogamy.
The hospital serving a city of 60,000 people shouldn't have a 30-bed cystic fibrosis ward (CF is an inborn error of metabolism) ... but Dewsbury needed one. (CF has a frequency of roughly 1 in 3000 in Northern Europe, so you'd expect 20 living cases in a town the size of Dewsbury: but they wouldn't need hospital beds simultaneously! The local frequency was much higher.) Nor should it have exotic conditions like familial hypobetalipoproteinaemia showing up in the population. Again, Dewsbury had that. In fact, Dewsbury was so notorious for genetic disorders that house officers and registrars training in the relevant fields got rotated there from the big teaching hospitals in Leeds (the nearest big city).
Upshot: if you get geographically isolated communities with religious cultures that discourage exogamy, you get really weird genetic disorders cropping up within surprisingly few generations.