Orphanet Journal of Rare Diseases最新文献

Background: Lymphangioleiomyomatosis (LAM) is a rare, multisystemic metastatic disease. Chemokines are implicated in promoting LAM cell migration and tumor progression. Our prior plasma proteomics identified elevated C-C motif chemokine ligand 14 (CCL14) in LAM, yet its role remains unexplored.

Methods: Proteomic analysis identified CCL14 as differentially expressed in LAM patients versus healthy controls. Single-cell RNA sequencing (scRNA-seq) of lung tissues (six LAM patients, five healthy donors) identified the cellular source of CCL14 and explored its functional pathways bioinformatically. ELISA-quantified plasma CCL14 levels were analyzed for correlations with clinical phenotypes and longitudinal disease progression in 53 LAM patients and 25 controls.

Results: Proteomics and scRNA-seq revealed upregulation of CCL14 in LAM patients, primarily localized to lymphatic and vascular endothelial cells. Functional enrichment linked CCL14 to proliferative (mTORC1, MYC), inflammatory (TNF-α/NF-κB), and chemotactic pathways. CellPhoneDB indicated CCL14 mediates interactions between endothelial cells and innate immune/alveolar epithelial cells, and between endothelial cells themselves, via ACKR2, CCR3 and CCR1. Clinically, plasma CCL14 levels were significantly elevated in LAM patients versus controls (p = 0.003). Subgroup analyses demonstrated higher CCL14 levels in patients with angiomyolipomas (AMLs) versus those without, and in CT grade III versus grade I/II. Critically, CCL14 predicted disease progression: baseline CCL14 levels were higher in progressive versus stable patients (p = 0.0266) and positively correlated with annual increase in the percentage of cystic lung volume (r = 0.4051, p = 0.0446).

Conclusions: CCL14 is a critical regulatory molecule within the LAM microenvironment and a promising biomarker for disease severity and progression.

Background: Fabry disease (FD) is a multisystemic, progressive, X-linked genetic disorder caused by dysfunction of the enzyme α-galactosidase A. Symptoms commonly present in childhood in classic patients. Prior studies in classic patients suggest primary presenting features include gastrointestinal (GI) symptoms such as abdominal pain, bloating, and diarrhea. In this longitudinal study, we collected annual questionnaires and medical records from families of 29 children between 3 months and 9.5 years old, including the Rome III questionnaire. We compared symptom detection of abdominal pain, constipation, diarrhea, and bloating via three methods: the Rome III, a simple review of symptoms questionnaire, and pediatrician notes including a review of systems.

Results: Both questionnaires elicited all GI symptoms more frequently than pediatrician notes (log rank test, p < 0.001). The two questionnaires had weaker agreement for constipation than other symptoms (per kappa statistic) and more similar detection at a younger age. After 24 months, the Rome III outperformed the simple review of symptoms questionnaire (Fisher's exact test, p < 0.001). Pediatrician notes never recorded bloating or severe episodes of abdominal pain.

Conclusions: Targeted questionnaires elicit early gastrointestinal symptoms in pediatric Fabry disease patients that would otherwise go unnoticed at a standard doctor's appointment. Based on manual analysis of questionnaire data, a list of questions is suggested to support pediatricians of young patients with FD in recognizing GI symptoms. Use of more targeted and specific questions regarding GI symptoms is warranted in pediatric appointments of patients with FD, with age-appropriate expansion of the questions at 24 months of age. Early detection of symptoms in this population is critical as individual treatment plans are based on symptom onset and as newborn screening is expanding.

Achondroplasia is the most common form of short-limbed short stature of genetic origin. Most people with achondroplasia live fully independent, productive, and socially engaged lives. However, the condition is associated with several potential medical complications. Individuals with achondroplasia may experience medical, functional, and psychosocial challenges at different times in their life. The goal for lifelong care of individuals with achondroplasia is to optimize their physical and mental health through provision of individualized care and to promote participation and inclusion in society. In this article, as a tool for individuals with achondroplasia, their families, and their healthcare team, we provide a guided overview of the 2022 International Consensus Statement for management and care of individuals with achondroplasia. The International Consensus Statement recommendations are based on current, best available knowledge. We provide commentary on the recommendations from the perspective of both patients and physicians through addressing medical/developmental considerations, the healthcare system, and psychosocial considerations.