This is a question about how doctors carry out diagnoses in practice, not one looking for medical answers.
My question is, statistically most cases are horses, but how do you find the zebras? According to Indiana University School of Medicine, a rare disease is defined by having less than 200,000 cases, and approximately 1 in 10 Americans has a rare disease. The discrepancy here is that while it is exceedingly unlikely to have any particular rare disease, there are enough of them that the odds of having any one are not that low. Evidently, doctors and nurses spend the vast majority of their time dealing with common and generally quite obvious conditions. Sepsis, vehicular accidents, heart issues, complications in childbirth, arthritis, falls, cancer, these are daily events, but rare diseases, while common in the aggregate, are each most likely to be seen by a given health care provider once or twice in their lifetime, and yet clearly there's still need to diagnose them effectively.
When presented with a patient who insists something is deeply wrong with some supporting evidence, seems impaired yet not under the influence of drugs or alcohol, and initial tests come back normal, what next?
How are rare diseases (or less-common-than-common diseases even) recognized and diagnosed?