Rare Disease Report

Chapter 2: Diagnosing a Rare Disease

A survey by Shire Pharmaceuticals and Global Genes, involving more than 1000 patients with rare diseases and the doctors who treat them, estimated that it takes an average of 7.6 years in the United States and 5.6 years in the United Kingdom for a patient with a rare disease to receive a correct diagnosis.1 During this time, the average patient will be misdiagnosed 2 or 3 times while visiting 4 primary care physicians and 4 specialists (on average).

An issue with these statistics is that the average patient does not convey the large variance observed by persons with rare disease; some are diagnosed within minutes or hours of being born, while it can take decades for others to receive their correct diagnosis. For example, late-onset Pompe disease is a genetic condition. The slow onset of symptoms, however, means many do not receive their diagnosis until their 30s or 40s. Interestingly, Pompe disease is now part of newborn screening, so the diagnostic delays will hopefully be much shorter for the next generation of patients.
More severe rare conditions are usually diagnosed quickly. Less severe conditions, although cumbersome and problematic, may take years to diagnose.

Delayed Diagnosis Is Common

With more than 25 million Americans with rare diseases, it is likely that most clinicians will encounter several of these patients during their career. Because there are approximately 7000 rare diseases, however, it is impossible to expect clinicians to know exactly which symptoms are unique to a rare condition compared with those that are more likely due to a common ailment. This is an issue not easily overcome. Two tips for doctors to consider when presented with a person that is difficult to diagnose are:
  1. If you are the investigating clinician and you do not know what a problem is, instead of wasting time trying to diagnose the condition, admit that the patient needs to be seen by someone with more experience with patients with rare disease and refer the patient to them.
  2. The patients themselves, and their caregivers, can be great assets to their doctors. As information on rare diseases has become more readily available, many patients and caregivers have begun to educate doctors on the possibility of a rare condition. That and the increased number of orphan drugs available, well-organized patient advocacy groups, and better search engines have helped increase the awareness of rare diseases.

A common story shared in the rare disease community is the notion that clinicians are taught in medical school to think like a rancher. If ranchers hear hoof beats, they assume that a horse is behind them and not a zebra. In most cases, when doctors see a series of symptoms, they assume they are related to a common ailment, not a rare one. In many cases, the doctor will be right in making that assumption, but after a second or third test comes back inconclusive, it is in the doctor’s and patient’s best interest to assume those hoof beats belong to a zebra, not a horse.


There are numerous resources available to help clinicians examining a patient with a series of symptoms that do not fit more common ailments. These include:

National Organization for Rare Disorders (NORD): rarediseases.org

A nonprofit organization founded by Abbey Meyers in 1983 soon after the passing of the Orphan Drug Act, NORD is considered the go-to resource for information on rare diseases for patients, caregivers, clinicians, and pharmaceutical professionals.

Genetic and Rare Diseases Information Center: rarediseases.info.nih.gov/GARD

This National Institutes of Health (NIH) site, which focuses on rare and genetic diseases, features an excellent and thorough list of rare diseases, along with information on those for which there are approved treatments.

Orphanet: orpha.net

Much like NORD, this European-based reference portal is an excellent source of information on rare diseases, orphan drugs, diagnostic tests, patient organizations, and expert medical opinion.

Undiagnosed Diseases Network: genome.gov/27550959/undiagnosed-diseases-network-udn/

This NIH-funded network of clinical research centers works to find a diagnosis for those patients for whom a doctor cannot make a diagnosis (or who have an unnamed disease).

Find Zebra: findzebra.com/

This relatively new site designed to help clinicians diagnose a rare disease allows clinicians to type in a phenotype or genotype and for patients to list their symptoms to possibly provide clues to a diagnosis.

  1. Rare Disease Impact Report: Insights from patients and the medical community. Shire and Global Genes. April 2013. Available at: globalgenes.org/wp-content/uploads/2013/04/ShireReport-1.pdf Accessed September 22, 2017

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