A disease is termed as ‘rare’ when it affects fewer than 1 in 2000 people. There are currently estimated to be over 7000 rare diseases, with 72% being genetic diseases. New conditions are continually being identified and often, due to the lack of scientific knowledge, there can be a delay in diagnosis and treatment which has a potentially significant impact on the patients’ quality of life as well as their families. The cause of the Rare Disease Day campaign is to achieve fair access to diagnosis, treatment and care for the people affected by a rare disease. In response to the call to raise awareness, we highlight key related research from the BMC Series. 

BMC Primary Care - “The healthcare system did fail me repeatedly”: a qualitative study on experiences of healthcare among Canadian women with Cushing’s syndrome

Cushing’s syndrome is a rare endocrine disorder caused by having too much cortisol in your body - a steroid hormone helping your body respond to stress. The incidence of Cushing’s syndrome is higher in women compared to men and it has a number of symptoms including weight gain, skin that bruises easily, fatigue and high blood pressure. 

The research focused on healthcare in Canada and the authors recruited 7 participants from Facebook support groups for Cushing’s Syndrome to carry out virtual interviews. The interview questions were focused around the participants' experiences with getting diagnosed with Cushing’s syndrome, their experience with the healthcare system before and after their diagnosis as well as their perception of body image and weight before and after their diagnosis.

During the analysis, the researchers found two key areas - the first being negative experiences in healthcare and secondly, women’s body image as connected to Cushing’s-related changes. The study concluded that a lack of patient centered care may impact Cushing’s syndrome being recognised and the diagnosis of it in a primary healthcare setting - they highlighted the need for further research on this topic. 

BMC Oral Health - Oral health and oral-health-related quality of life in people with X-linked hypophosphatemia

X-linked hypophosphatemia (XLH), also known as X-linked hypophosphatemic rickets, is a rare inherited disease that affects bones as well as causing dental abnormalities. The disease is caused by a mutation which means a change in the X-linked phosphate-regulating endopeptidase (PHEX) gene. 

For people with XLH, it can have a large impact on their oral health. The disease causes recurrent abscesses and fistulas due to the impaired mineralization of the teeth which allows bacteria to reach the pulp and cause cell death, known as pulp necrosis. In addition to this increased risk of pulp necrosis, there is also an increased risk of periodontitis, also known as gum disease. Overall these dental abnormalities mean more risk of premature tooth loss. 

A study published in BMC Oral Health examined oral-health-related quality of life in people with the disease with a total of 26 participants. They answered the German short form of the Oral Health Impact Profile (OHIP-14) questionnaire as well as having their oral health being examined using the Physical Oral Health Index (PhOX). 

The authors found that both oral health and oral-health-related quality of life of people with XLH were reduced compared to the general population in Germany. The study highlighted the need for XLH patients to maintain good oral hygiene as well as regular dental check-ups  to detect oral manifestations as early as possible.  

BMC Medical Informatics and Decision Making - A hybrid framework with large language models for rare disease phenotyping

Given the low prevalence and diverse range of symptoms of rare diseases, diagnosis and treatment can be difficult. This often leads to a long delay in appropriate treatment which can mean missed opportunities for early intervention as well as unnecessary medical procedures. As a result, patients with rare diseases, as well as their families, deal with uncertainty and patients may see multiple specialists and undergo several tests before being diagnosed. This also has an impact on healthcare systems and resources. Therefore, there is a need for novel approaches to improve rare disease identification and diagnosis. 

In a study published in BMC Medical Informatics and Decision Making, the researchers introduced a novel hybrid framework combining dictionary-based natural language processing (NLP) tools with large language models (LLMs) to improve rare disease identification. Each model had their strengths and limitations but overall, the hybrid framework showed superior performance compared to other NLP tools and standalone LLMs. 

The hybrid framework promises to be useful for rare disease identification in clinical practice in the future. The researchers conclude the need to enhance the robustness and adaptability of their novel approach given the evolving nature of medical vocabulary - a focus for future research. However, they highlight that collaborations between experts, such as computational linguists and ontology developers, will be crucial to integrating their method into clinical practice. 

BMC Cancer - Validation of biomarkers and clinical scores for the detection of uterine leiomyosarcoma: a case-control study with an update of pLMS

A uterine leiomyosarcoma (uLMS) is a rare and highly malignant tumor growing from the smooth muscle lining of the walls of the uterus. A major clinical challenge is discriminating them from benign uterine masses, such as leiomyoma (LM), as they often present with the same symptoms which can mean misdiagnosis and incorrect surgical procedures being carried out. This may impact survival time and so it is crucial to find a reliable way to detect uLMS from LM. 

A study published in BMC Cancer aimed to validate and update a preoperative clinical scoring system using a case-control study design involving 90 retrospective uLMS cases and 659 LM cases, building on their previous 2019 study. In addition, the researchers investigated the ability of blood markers to be used to discriminate uLMS from LM; they investigated the levels of serum lactate dehydrogenase (LDH), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR).

The analysis found that the preoperative clinical scoring system showed stable discriminatory ability and all 3 of the biomarkers investigated (LDH, NLR and PLR) provided further evidence to differentiate uLMS from LM alongside clinical data. A limitation of the study is its predominantly retrospective nature; however, the rarity of uLMS means it has not been possible for a prospective study to be carried out yet. The study validates that the updated preoperative clinical scoring system is a cost-effective tool which can help prevent uLMS being misdiagnosed as LM alongside other diagnostic measures.