German Porphyria Registry (PoReGer)-Background and Setup.

Porphyrias, as most rare diseases, are characterized by complexity and scarcity of knowledge. A national registry in one of the largest European populations that prospectively collects longitudinal clinical and laboratory data are an important and effective tool to close this gap. The German Porphyria Registry (PoReGer) was founded by four centers with longstanding expertise in the field of porphyrias and rare diseases (Charité-Universitätsmedizin Berlin, Porphyria Center Saxony Chemnitz, University Medical Center Hamburg-Eppendorf, University Medical Center Göttingen) and the German reference laboratory for porphyria, and is supported by the largest German porphyria patient organization. A specified data matrix for three subgroups (acute, chronic blistering cutaneous, acute non-blistering cutaneous) includes data on demographics, specific porphyria-related symptoms, clinical course, general medical history, necessary follow-up assessments (including laboratory and imaging results), symptomatic and disease-modifying therapies, and side-effects. Additionally, the registry includes patient-reported outcome measures on quality of life, depression, and fatigue. PoReGer aims to broaden and deepen the understanding on all porphyria-related subjects. We expect these data to significantly improve the management and care of porphyria patients. Additionally, the data can be used for educational purposes to increase awareness, for the planning of healthcare services, and for machine learning algorithms for early detection of porphyrias.

Detect Acute Porphyrias in Emergency Departments (DePorED) - a pilot study.

BACKGROUND: Acute porphyrias (APs) are a group of rare metabolic diseases related to a disturbed heme biosynthesis. Symptoms may first occur as life threatening attacks, comprising abdominal pain and/or variable neuro-psychiatric symptoms, thus leading to presentation in emergency departments (ED) first. Due to the low prevalence, diagnosis of AP is often missed, even after readmission to the ED. Therefore, strategies are needed to consider APs in ED patients with unexplained abdominal pain, especially since early and adequate treatment will avoid an unfavorable clinical course. Aim of this prospective study was to investigate the prevalence of APs in ED patients and thus, addressing feasibility of screening for rare diseases, such as APs in the real life setting. METHODS: From September 2019 to March 2021, patients presenting to the ED of three German tertiary care hospitals with moderate to severe prolonged abdominal pain (Visual Analog Scale, VAS > 4 out of 10 points) not otherwise explained were screened and prospectively enrolled. In addition to standard of care (SOC) diagnostics a blood and urine sample for plasma fluorescence scan and biochemical porphyrin analysis were sent to a certified German porphyria laboratory. RESULTS: Overall, of 653 screened patients, 68 patients (36 females; mean age 36 years) were included for biochemical porphyrin analysis. No patient with AP was detected. The most frequent discharge diagnoses included "abdominal and digestive symptoms" (n = 22, 32%), "gastrooesophageal diseases" (n = 18, 27%), "infectious bowel disease" (n = 6, 9%) and "biliopancreatic diseases" (n = 6, 9%). Although not primarily addressed, we observed an increase in knowledge of the ED staffs at all study sites regarding our screening algorithm and thus, awareness for APs. CONCLUSIONS: To the best of our knowledge, we performed the first prospective screening project for APs in the ED. Although we detected no patient with AP in this study, we demonstrated the feasibility of a multicenter screening process for APs by building up a well-working infrastructure comprising laboratory testing as well as data management. This enables the set-up of a larger scale revised follow-up study with a central focus on structured education, thus, possibly acting as blueprint for other rare diseases.

Inhomogeneous distribution of Alzheimer pathology along the isocortical relief. Are cortical convolutions an Achilles heel of evolution?

Alzheimer's disease (AD) is neuropathologically characterized by neuritic plaques and neurofibrillary tangles. Progression of both plaques and tangles throughout the brain follows a hierarchical distribution which is defined by intrinsic cytoarchitectonic features and extrinsic connectivity patterns. What has less well been studied is how cortical convolutions influence the distribution of AD pathology. Here, the distribution of both plaques and tangles within subsulcal gyral components (fundi) to components forming their top regions at the subarachnoidal brain surface (crowns) by stereological methods in seven different cortical areas was systematically compared. Further, principle differences in cytoarchitectonic organization of cortical crowns and fundi that might provide the background for regionally selective vulnerability were attempted to identify. It was shown that both plaques and tangles were more prominent in sulcal fundi than gyri crowns. The differential distribution of pathology along convolutions corresponds to subgyral differences in the vascular network, GFAP-positive astrocytes and intracortical and subcortical connectivity. While the precise mechanisms accounting for these differences remain open, the presence of systematic inhomogeneities in the distribution of AD pathology along cortical convolutions indicates that the phylogenetic shaping of the cortex is associated with features that render the human brain vulnerable to AD pathology.