Congenital Disorders

This chapter is devoted to specific diseases presenting usually in early infancy or childhood as a result of disruption in the normal development of the cornea and its associated structures. These disorders may develop due to one or a combination of various genetic, infectious, inflammatory, toxic, metabolic, traumatic, or mechanical processes and may occur at any time during tissue induction, differentiation, and maturation. Adjacent structures (anterior chamber angle, iris, and lens) can be impacted too. Congenital limbal stem cell deficiency is usually associated with aniridia and ectodermal dysplasia. Aniridia can occur in a sporadic or familial form. The familial inheritance pattern of aniridia is predominantly autosomal dominant. The aniridia phenotype varies depending on the mutation present. Interesting ocular congenital disorders associated with Neurofibromatosis, Axenfeld-Rieger syndrome, Icthyosis are shown in this chapter. It presents a rare case of porphyria-associated sclerocorneal melting with before and after treatment photos.

The geontological time-spaces of late modern war

Attending to connections between serious health conditions (cancers and congenital disorders) and weapons residues in Iraq, Afghanistan and Gaza, this article develops a geographical agenda for examining power in late modern war from the perspective of the ground and the life it sustains. A case is made for understanding the time-spaces of war as not compressed, vertical or remote but enduring, pedospheric and proximate in which violence emerges through processes (carcinogenic and teratogenic) that transcend boundaries between ‘life’ ( bios) and ‘nonlife’ ( geos). Such are the geontological time-spaces of late modern war that geographers – in both ‘physical’ and ‘human’ sub-fields – are uniquely equipped to examine.

Comparison of Intramedullary Magnetic Nail, Monolateral External Distractor, and Spatial External Fixator in Femur Lengthening in Adolescents with Congenital Diseases

The aim of this study is to evaluate the course of the treatment and clinical and functional outcomes of femur lengthening in adolescents with congenital disorders by the application of different surgical methods. This retrospective study comprised 35 patients (39 procedures). A total of 11 patients underwent femur lengthening with the use of the intramedullary magnetic nail (IMN) Precise 2 (NuVasive, San Diego, CA, USA), 7 patients (11 procedures) with the use of the monolateral external distractor Modular Rail System (MRS) (Smith and Nephew, Memphis, TN, USA), and 17 with the use of the computer-assisted external fixator Taylor Spatial Frame (TSF) (Smith and Nephew, Memphis, TN, USA). The inclusion criteria were as follows: (1) congenital femoral length deficiency without any axial deformities and (2), independently of the finally applied treatment, the technical possibility of use of each of the analyzed methods. The distraction index did not differ significantly between the groups (p = 0.89). The median lengthening index was the lowest in the IMN group (24.3 d/cm; IQR 21.8–33.1) and statistically different in comparison to the MRS (44.2 d/cm; IQR 42–50.9; p < 0.001) and the TSF groups (48.4 d/cm; IQR 38.6–63.5; p < 0.001). Similarly, the consolidation index in the IMN group (12.9 d/cm; IQR 10.7–21.3) was statistically lower than that in the MRS (32.9 d/cm; IQR 30.2–37.6; p < 0.001) and the TSF (36.9 d/cm; IQR 26.6–51.5; p < 0.001) groups. This study indicates that IMN is a more valuable method of treatment for femoral length discrepancy without axial deformity than MRS and TSF in complication rate and indexes of lengthening and consolidation.

A novel fission yeast platform to model N-glycosylation and the bases of congenital disorders of glycosylation Type I

Congenital Disorders of Glycosylation Type I (CDG-I) are inherited human diseases caused by deficiencies in lipid-linked oligosaccharide (LLO) synthesis or the glycan transfer to proteins during N-glycosylation. We constructed a platform of 16 Schizosaccharomyces pombe mutant strains that synthesize all possible theoretical combinations of LLOs containing three to zero Glc and nine to five Man. The occurrence of unexpected LLOs suggested the requirement of specific Man residues for glucosyltransferases activities. We then quantified protein hypoglycosylation in each strain and found that in S. pombe the presence of Glc in the LLO is more relevant to the transfer efficiency than the amount of Man residues. Surprisingly, a decrease in the number of Man in glycans somehow improved the glycan transfer. The most severe hypoglycosylation was produced in cells completely lacking Glc and having a high number of Man. This deficiency could be reverted by expressing a single subunit OST with a broad range of substrate specificity. Our work shows the usefulness of this new S. pombe set of mutants as a platform to model the molecular bases of human CDG-I diseases.

Getting Sugar Coating Right! The Role of the Golgi Trafficking Machinery in Glycosylation

The Golgi is the central organelle of the secretory pathway and it houses the majority of the glycosylation machinery, which includes glycosylation enzymes and sugar transporters. Correct compartmentalization of the glycosylation machinery is achieved by retrograde vesicular trafficking as the secretory cargo moves forward by cisternal maturation. The vesicular trafficking machinery which includes vesicular coats, small GTPases, tethers and SNAREs, play a major role in coordinating the Golgi trafficking thereby achieving Golgi homeostasis. Glycosylation is a template-independent process, so its fidelity heavily relies on appropriate localization of the glycosylation machinery and Golgi homeostasis. Mutations in the glycosylation enzymes, sugar transporters, Golgi ion channels and several vesicle tethering factors cause congenital disorders of glycosylation (CDG) which encompass a group of multisystem disorders with varying severities. Here, we focus on the Golgi vesicle tethering and fusion machinery, namely, multisubunit tethering complexes and SNAREs and their role in Golgi trafficking and glycosylation. This review is a comprehensive summary of all the identified CDG causing mutations of the Golgi trafficking machinery in humans.