“It was a lot Tougher than I Thought It would be”. A Qualitative Study on the Changing Nature of Being a Hemophilia Carrier

Studies on carriers of genetic disorders mainly focus on the process of genetic testing and reproductive choices, and less on how psychosocial aspects of being a carrier change over time. Our study sought to understand more about the psychosocial aspects of hemophilia carrier status, and thereby improve counseling aiming to advance carriers' quality of life and well-being. We analyzed 16 in-depth interviews from women who were carriers of hemophilia and had a son with hemophilia. Three themes emerged: Guilt and sorrow across generations; the choices and future consequences of genetic testing; and preparing to have a child with hemophilia. Experience with being a hemophilia carrier is a process that changes over time while feelings of guilt and sorrow run across generations. The carrier status may create "mothers-in-waiting" living at risk of having a sick child or not. The women think they are prepared to have a son with hemophilia, but experience more sadness than they expect when a son is diagnosed. Our findings suggest that health professionals, especially clinical geneticists and genetic counselors, carriers, families and patient organizations need to be aware that women's experiences of being a carrier of hemophilia changes during the biographical life course. The women may benefit from several rounds of genetic counseling at different stages of life

Mechanisms and consequences of carbamoylation.

Protein carbamoylation is a non-enzymatic post-translational modification that binds isocyanic acid, which can be derived from the dissociation of urea or from the myeloperoxidase-mediated catabolism of thiocyanate, to the free amino groups of a multitude of proteins. Although the term 'carbamoylation' is usually replaced by the term "carbamylation" in the literature, carbamylation refers to a different chemical reaction (the reversible interaction of CO2 with α and ε-amino groups of proteins). Depending on the altered molecule (for example, collagen, erythropoietin, haemoglobin, low-density lipoprotein or high-density lipoprotein), carbamoylation can have different pathophysiological effects. Carbamoylated proteins have been linked to atherosclerosis, lipid metabolism, immune system dysfunction (such as inhibition of the classical complement pathway, inhibition of complement-dependent rituximab cytotoxicity, reduced oxidative neutrophil burst, and the formation of anti-carbamoylated protein antibodies) and renal fibrosis. In this Review, we discuss the carbamoylation process and evaluate the available biomarkers of carbamoylation (for example, homocitrulline, the percentage of carbamoylated albumin, carbamoylated haemoglobin, and carbamoylated low-density lipoprotein). We also discuss the relationship between carbamoylation and the occurrence of cardiovascular events and mortality in patients with chronic kidney disease and assess the effects of strategies to lower the carbamoylation load