China
Africa
Explore chapters and articles related to this topic
Role of Ascorbate and Dehydroascorbic Acid in Metabolic Integration of the Cell
Published in Qi Chen, Margreet C.M. Vissers, Vitamin C, 2020
Gábor Bánhegyi, András Szarka, József Mandl
A further possible human example of ascorbate compartmentalization disease is arterial tortuosity syndrome (ATS). This rare congenital connective tissue disorder manifested in the tortuosity of main arteries and thoracic aneurysm formation. The genetic background is the mutation of the GLUT10 gene [20]. The GLUT10 protein has been reported to be present in the endomembranes (ER and Golgi) and mitochondrial membranes [20,30,46,71]. GLUT10 is able to transport DHA, as it was demonstrated in mitochondria [46], in plasma membrane permeabilized fibroblasts, and in reconstituted GLUT10-containing proteoliposomes [61]. The absence of GLUT10 in the ER might explain the alterations of the extracellular matrix due to impaired hydroxylation of proteins in ATS [71]. Its missing function in the nuclear envelope can hamper the nuclear import of vitamin C. A recent report showed that the ascorbate concentration was lower in the nucleus of ATS fibroblasts. Consequently, the global methylation/hydroxymethylation pattern of DNA was also changed, and gene-specific alterations were also found [62]. The findings raise the possibility that epigenetic effects contribute to the pathogenesis as well. In summary, the different hypotheses on ATS pathogenesis are uniform, postulating altered DHA transport into subcellular compartments.
Pharmacological resources, diagnostic approach and coordination of care in joint hypermobility-related disorders
Published in Expert Review of Clinical Pharmacology, 2018
No specific drug with proved efficacy in reducing the hemorrhagic risk and soft tissue fragility is available for JHRDs. General measures of prevention remain the most effective strategy. In patients with a positive history of significant skin and capillary fragility (this often happens in those affected by classical, vascular and dermatosparaxis EDS), the use of protective pads and bondages on sites with major risk (knees, pretibial areas, elbows, and forehead) can be considered especially in children involved in social and sport activities. Avoiding contact sports and heavy exercise may be considered in patients with extensive easy bruising and extreme skin fragility. In those with molecularly proved vascular EDS, and the other EDS types with increased arterial fragility (e.g. classical EDS with COL1A1 mutations and kyphoscoliotic EDS), as well as disorders of the TGFβ pathway, arterial tortuosity syndrome and cutis laxae with vascular fragility, drugs interfering the hemostatic process should be avoided or prescribed with care due an increased risk of hemorrhagic catastrophic events. Among these drugs there are acetylsalicylic acid, some non-steroidal anti-inflammatory drugs (e.g. ibuprofen), coumarins, heparins, and pentasaccharides. Invasive endovascular diagnostic and therapeutic interventions should be performed cautiously and surgery should always consider the risk of deadly complications due to arterial fragility. Some general recommendations for surgery in EDS and, more specifically, vascular EDS have been published [77].
Ophthalmic findings in patients with arterial tortuosity syndrome and carriers: A case series
Published in Ophthalmic Genetics, 2018
Joshua S. Hardin, Yuri A. Zarate, Bert Callewaert, Paul H. Phillips, David B. Warner
Arterial tortuosity syndrome is a rare autosomal recessive connective tissue disorder.1,13,17,20 In ATS, GLUT10 deficiency is thought to increase TGF-β signaling which causes elastin fragmentation and poor cellular differentiation.3,21 The deficiency results in stenosis, aneurysms, and dissection of large- and medium-sized vessels.22 In addition, skin laxity, inguinal hernias, joint laxity, and skeletal overgrowth reflect generalized connective tissue involvement as seen in most inherited elastinopathies.1,2,4–17 Some case reports have mentioned ocular involvement including myopia, keratoconus, and keratoglobus (Table 1), but these reports lack complete and well-documented ophthalmologic examinations and references to ocular pathology were often made based on historical information alone.1,2,10,12,18