"Background: Rare disease, also known as orphan disease, is a general term for diseases with extremely low incidence rate and few patient. So far, over 10,000 rare diseases have been identified globally. It is estimated that between 260 million to 450 million people worldwide are affected by rare diseases. However, difficulties such as recruiting rare disease patients, lack of understanding of the natural progression of diseases, small numbers within rare disease patient communities, significant clinical heterogeneity, and the absence of sensitive outcome indicators have led to a scarcity of high-quality clinical research on rare diseases. Therefore, some questions about the diagnosis and treatment of rare diseases have been raised. How many rare diseases have clear diagnosis and treatment methods? How many published guidelines of rare diseases? How do these guidelines apply existing evidence related to rare diseases? Can the quality of these guidelines meet the diagnostic and treatment needs of rare diseases?

Objective: This article aims to understand the publication of rare disease guidelines and their current application of evidence and assess their methodological and reporting quality.

Methods: The articles has been retrieved from PubMed, Trip Medical Database and CNKI in September 2023. The guideline for rare disease is eligible. And we only include the articles in English or Chinese. Theses studies will be selected manually and assessed by two independent reviewers and any objection was consulted by a third reviewer. The AGREE II was used to reflect the methodological quality of guidelines, and the RIGHT checklist was adopted to assess their reporting quality.

Results: 17,275 studies were obtained in electronic database. 1,894 studies were included through primary screening. The result will be finished before July 2024.

Conclusion: This review will help us to comprehensively understand the current status of rare disease guidelines, identify their existing issues, and promote the development.