Correction to: 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency: one disease - many faces

Correction to: Orphanet Journal of Rare Diseases (2020) 15:48 https://doi.org/10.1186/s13023-020-1319-

Biomarkers for Drug Development in Propionic and Methylmalonic Acidemias

There is an unmet need for the development and validation of biomarkers and surrogate endpoints for clinical trials in propionic acidemia (PA) and methylmalonic acidemia (MMA). This review examines the pathophysiology and clinical consequences of PA and MMA that could form the basis for potential biomarkers and surrogate endpoints. Changes in primary metabolites such as methylcitric acid (MCA), MCA:citric acid ratio, oxidation of 13C-propionate (exhaled 13CO2), and propionylcarnitine (C3) have demonstrated clinical relevance in patients with PA or MMA. Methylmalonic acid, another primary metabolite, is a potential biomarker, but only in patients with MMA. Other potential biomarkers in patients with either PA and MMA include secondary metabolites, such as ammonium, or the mitochondrial disease marker, fibroblast growth factor 21. Additional research is needed to validate these biomarkers as surrogate endpoints, and to determine whether other metabolites or markers of organ damage could also be useful biomarkers for clinical trials of investigational drug treatments in patients with PA or MMA. This review examines the evidence supporting a variety of possible biomarkers for drug development in propionic and methylmalonic acidemias

Natural Hazards under Climate Change Conditions: A Case Study of Expectations and their Normative Significance in Protecting Alpine Communities

Climate change increases the frequency and intensity of certain kinds of natural hazard events in alpine areas. This interdisciplinary study addresses the hypothetical possibility of relocating the residents of three alpine areas in Austria: the Sölk valleys, the Johnsbach valley, and the St. Lorenzen/Schwarzenbach valleys. Our particular focus is on these residents’ expectations about such relocations. We find that (1) many residents expect that in the next decades the state will provide them with a level of natural hazards protection, aid, and relief that allows them to continue to live in these valleys; (2) this expectation receives some legal protection but only when it is associated with fundamental rights; and (3) the expectation is morally significant, i.e., it ought to be considered in assessing the moral rightness or justness of relocation policies. These results suggest legal changes and likely extend to many other (Austrian) alpine areas as well

An Autosomal-Recessive Form of Cutis Laxa Is Due to Homozygous Elastin Mutations, and the Phenotype May Be Modified by a Heterozygous Fibulin 5 Polymorphism

Cutis laxa (CL) is a heterogeneous group of connective tissue disorders characterized by loose, sagging skin and variable involvement of other organs. Autosomal-dominant forms are relatively mild, and may be caused by mutations in the elastin gene, whereas the more severe recessive forms have been associated with mutations in the fibulin 4 and fibulin 5 genes, as well as in a vesicular ATPase subunit. We describe here a previously unreported autosomal-recessive form of CL caused by homozygous recessive mutations in exon 12 of the elastin gene (p.P211S) in three patients from two related consanguineous Syrian families. Furthermore, we found that the presence of a polymorphism in the fibulin 5 gene in one of the patients seems to modify the phenotype, producing more severe symptoms. This polymorphism (p.L301M) was associated with mild symptoms in the mother of the patient, who was heterozygous for both the elastin and fibulin 5 mutations. To our knowledge, autosomal-recessive CL owing to homozygous mutations in the elastin gene has not been reported previously