A resource of lipidomics and metabolomics data from individuals with undiagnosed diseases.

Every year individuals experience symptoms that remain undiagnosed by healthcare providers. In the United States, these rare diseases are defined as a condition that affects fewer than 200,000 individuals. However, there are an estimated 7000 rare diseases, and there are an estimated 25-30 million Americans in total (7.6-9.2% of the population as of 2018) affected by such disorders. The NIH Common Fund Undiagnosed Diseases Network (UDN) seeks to provide diagnoses for individuals with undiagnosed disease. Mass spectrometry-based metabolomics and lipidomics analyses could advance the collective understanding of individual symptoms and advance diagnoses for individuals with heretofore undiagnosed disease. Here, we report the mass spectrometry-based metabolomics and lipidomics analyses of blood plasma, urine, and cerebrospinal fluid from 148 patients within the UDN and their families, as well as from a reference population of over 100 individuals with no known metabolic diseases. The raw and processed data are available to the research community so that they might be useful in the diagnoses of current or future patients suffering from undiagnosed disorders.

Characteristics of undiagnosed diabetes in men and women under the age of 50 years in the Indian subcontinent: the National Family Health Survey (NFHS-4)/Demographic Health Survey 2015-2016.

OBJECTIVE: Prior studies examining diabetes prevalence in India have found that nearly 50% of the diabetes population remains undiagnosed; however, the specific populations at risk are unclear. RESEARCH DESIGN AND METHODS: First, we estimated the prevalence of undiagnosed diabetes in India for 750 924 persons between the ages of 15 years and 50 years who participated in the National Family Health Survey (NFHS-4)/Demographic Health Survey (2015-2016), a cross-sectional survey of all 29 states and 7 union territories of India. We defined 'undiagnosed diabetes' as individuals who did not know about their diabetes status but had high random (≥200 mg/dL) or fasting (≥126 mg/dL) blood glucose levels. Second, using Poisson regression, we associated 10 different factors, including the role of healthcare access, and undiagnosed diabetes. Third, we examined the association of undiagnosed diabetes with other potential comorbid conditions. RESULTS: The crude prevalence of diabetes for women and men aged 15-50 years was 2.9%, 95% CI 2.9% to 3.1%, with self-reported diabetes prevalence at 1.7%, 95% CI 1.6 to 1.8. The overall prevalence of undiagnosed diabetes for 15-50 year olds was at 1.2%, 95% CI 1.2% to 1.3%. Forty-two per cent, 95% CI 40.7% to 43.4% of the individuals with high glucose levels were unaware of their diabetes status. Approximately 45%, 95% CI 42.9% to 46.4% of undiagnosed diabetes population had access to healthcare. Men, younger individuals, and those with lower levels of education were most at risk of being undiagnosed. Geographically, the Southern states in India had a significantly higher prevalence of undiagnosed diabetes despite having nearly universal access to healthcare. Risk factors combined with random glucose could predict undiagnosed diabetes (area under the curve of 97.8%, 95% CI 97.7% to 97.8%), Nagelkerke R2 of 66%). CONCLUSION: Close to half (42%) of the people with diabetes in India are not aware of their disease status, and a large subset of these people are at risk of poor detection, despite having health insurance and/or having access to healthcare. Younger age groups and men are the most vulnerable.

A comprehensive, multidisciplinary, precision medicine approach to discover effective therapy for an undiagnosed, progressive, fibroinflammatory disease.

Precision medicine has generated diagnoses for many patients with challenging undiagnosed disorders. Some individuals remain without a diagnosis despite comprehensive testing, and this impedes their treatment. This report addresses the role of personalized medicine in identifying effective therapy for an undiagnosed disease. A 22-year-old woman presented with chronic severe recurrent trismus, facial pain, progressive multicentric inflammatory and fibrotic masses, and high C-reactive protein. Sites of disease included the pterygomaxillary region, masseter muscles, mandible, lung, pericardium, intrabdominal cavity, and retroperitoneum. A diagnosis was not established after an extensive assessment, including multiple biopsies. The patient was subsequently evaluated under the Undiagnosed Diseases Program at the National Institutes of Health. Large scale genotyping, proteomic studies, and in vitro and gene expression analyses of fibroblasts obtained from a major disease locus were performed. Germline genetic testing did not identify strong candidate genes; proteomic studies of the patient's serum and bronchoalveolar lavage fluid and gene expression analyses of her cells were consistent with dysregulation of the tumor necrosis factor-alpha pathway. The patient's cultured fibroblasts were incubated with selected drugs, and cell proliferation was inhibited by hydroxychloroquine. Treatment of the patient with hydroxychloroquine conferred prolonged beneficial clinical effects, including stabilization of trismus and reduction of corticosteroid dose, C-reactive protein, and size of masses. This case represents an example of precision medicine applied to discover effective treatments for individuals with enigmatic undiagnosed disorders.