Cellular uptake of cobalamin: transcobalamin and the TCblR/CD320 receptor.

Elevated methylmalonic acid in five asymptomatic newborns whose fibroblasts showed decreased uptake of transcobalamin-bound cobalamin (holo-TC), suggested a defect in the cellular uptake of cobalamin. Analysis of TCblR/CD320, the gene for the receptor for cellular uptake of holo-TC, identified a homozygous single codon deletion, c.262_264GAG (p.E88del), resulting in the loss of a glutamic acid residue in the low-density lipoprotein receptor type A-like domain. Inserting the codon by site-directed mutagenesis fully restored TCblR function.

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Positive newborn screen for methylmalonic aciduria identifies the first mutation in TCblR/CD320, the gene for cellular uptake of transcobalamin-bound vitamin B12†

Transcobalamin (TC) transports cobalamin from blood into cells. TC deficiency is a rare autosomal recessive disorder usually presenting in early infancy with failure to thrive, weakness, diarrhoea, pallor, anemia, and pancytopenia or agammaglobulinemia. It can sometimes resemble neonatal leukemia or severe combined immunodeficiency disease. Diagnosis of TC deficiency is suspected based on megaloblastic anemia, elevation of total plasma homocysteine, and blood or urine methylmalonic acid. It is confirmed by studying the synthesis of TC in cultured fibroblasts, or by molecular analysis of the TCN2 gene. TC deficiency is treatable with supplemental cobalamin, but the optimal type, route and frequency of cobalamin administration and long term patient outcomes are unknown. Here we present a series of 30 patients with TC deficiency, including an update on multiple previously published patients, in order to evaluate the different treatment strategies and provide information about long term outcome. Based on the data presented, current practice appears to favour treatment of individuals with TC deficiency by intramuscular injections of hydroxy- or cyanocobalamin. In most cases presented, at least weekly injections (1 mg IM) were necessary to ensure optimal treatment. Most centres adjusted the treatment regimen based on monitoring CBC, total plasma homocysteine, plasma and urine methylmalonic acid, as well as, clinical status. Finally, continuing IM treatment into adulthood appears to be beneficial.

Update on transcobalamin deficiency: clinical presentation, treatment and outcome.

The catalytic properties of many enzymes depend on the participation of vitamins as obligatory cofactors. Vitamin B12 (cobalamin) and folic acid (folate) deficiencies in infants and children classically present with megaloblastic anemia and are often accompanied by neurological signs. A number of rare inborn errors of cobalamin and folate absorption, transport, cellular uptake, and intracellular metabolism have been delineated and identification of disease-causing mutations has improved our ability to diagnose and treat many of these conditions. Two inherited defects in biotin metabolism are known, holocarboxylase synthetase and biotinidase deficiency. Both lead to multiple carboxylase deficiency manifesting with metabolic acidosis, neurological abnormalities, and skin rash. Thiamine-responsive megaloblastic anemia is characterized by megaloblastic anemia, non-type I diabetes, and sensorineural deafness that responds to pharmacological doses of thiamine (vitamin B1). Individuals affected with inherited vitamin E deficiencies including ataxia with isolated vitamin E deficiency and abetalipoproteinemia present with a spinocerebellar syndrome similar to patients with Friedreich's ataxia. If started early, treatment of these defects by oral or parenteral administration of the relevant vitamin often results in correction of the metabolic defect and reversal of the signs of disease, stressing the importance of early and correct diagnosis in these treatable conditions.

Vitamin-responsive disorders: cobalamin, folate, biotin, vitamins B1 and E.

Transcobalamin (transcobalamin II, TC) transports plasma vitamin B(12) (cobalamin, Cbl) into cells. TC deficiency is a rare autosomal recessive disorder causing intracellular Cbl depletion, which in turn causes megaloblastic bone marrow failure, accumulation of homocysteine and methylmalonic acid, and methionine depletion. The clinical presentation reflects intracellular Cbl defects, with early-onset failure to thrive with gastrointestinal symptoms, pancytopenia, and megaloblastic anemia, sometimes followed by neurological complications. We report the clinical, biological, and molecular findings and the outcome in five TC-deficient patients. The three treated early had an initial favorable outcome, whereas the two treated inadequately had late-onset severe neuro-ophthalmological impairment. Even if the natural course of the disease over time might also result in late-onset symptoms in the aggressively treated patients, these data emphasize that TC deficiency is a severe disorder requiring early detection and probably long-term aggressive therapy. Mutation analysis revealed six unreported mutations in the TCN2 gene. In silico structural analysis showed that these mutations disrupt the Cbl-TC interaction domain and/or the putative transcobalamin-transcobalamin receptor interaction domain.

Should transcobalamin deficiency be treated aggressively

Transcobalamin II deficiency at birth.

A firefighter in the wildland fields spends an average of 8 to 16 h during which he encounters enormous physical effort and very demanding outdoor conditions of high temperatures. Research shows that the most common injuries are due to the occurrence of heat stress, and not due to lack of protection against burns. Therefore, for this very specific field of firefighting, it is necessary to provide clothing that will, in addition to adequate flame protection, provide good comfort properties such as lightweight suits, good porosity and breathability, so that gaseous sweat and heat generated by body heating can be released into the environment. The aim of this study was to determine the influence of structural parameters of multi-weft woven fabrics on two mutually contradictory properties—breathability and thermal protection. When designing fabrics, the goal was to produce a structure with a high proportion of volume pores, which, regardless of the increased volume of the fabric, insure the fabric mass would be acceptably small. Volume pores in the fabric have two roles—as a heat insulator and as an inhibitor of the breathability of the material. The analysis of the obtained results showed that the thickness and mass of the fabric have a greater influence on the water vapor resistance, while the heat transmission property is more affected by the thickness, porosity and fiber content.

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Thermal Protective Properties and Breathability of Multilayer Protective Woven Fabrics for Wildland Firefighting

This research aimed to test a newly developed 3D fabric for use in a hospital sterilization unit as a packaging material. Two basic properties were tested: the efficiency of the microbial barrier, and the bursting strength of the woven fabric, determined with a steel ball. Material deformations caused by bursting are common in medical sterilization, as a consequence of the packaging of the medical tools needed in surgery. Six 3D-fabric samples were woven from the same warp, with three weft densities and in two different weaves. The weaving conditions and other construction characteristics of the fabrics were the same. To determine the effectiveness of the microbial barrier, bacterial endospores of an apathogenic species of the genus Bacillus, Geobacillus stearothermophilus and Bacillus atrophaeus, were used. Mechanical testing of the 3D-woven fabric, i.e., the bursting strength of the fabric using a steel ball, was carried out according to the standard method. The results showed the exceptional puncture strength of the woven fabrics and their formation of an effective microbial barrier, i.e., complete impermeability to microorganisms in five samples, which is the main condition for possible use as a packaging material in medical sterilization. Sample 3tp did not provide an effective microbial barrier and did not meet the basic requirements for use in medical sterilization.

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Application of 3D-Woven Fabrics for Packaging Materials for Terminally Sterilized Medical Devices

The development and application of new types of fibres and their wider application influence the continuous invention of a more economical starching process, as one of the most expensive stages in the technological process of woven fabric production. For example, aramid fibres are increasingly used in clothing with effective protection from mechanical, thermal and abrasion exposure. Simultaneously, comfort and regulation of metabolic heat are extremely important, and this is achieved by using cotton woven fabrics. For such a woven fabrics to satisfy the protective properties and the possibility of all-day wear, fibre is needed, and thus a yarn, that will enable the efficient production of fine, light and comfortable protective woven fabrics. This paper investigates the influence of starching on the mechanical properties of aramid yarns and their comparison to cotton yarns of the same fineness. This will lead to knowledge about the efficiency and necessity of aramid yarn starching. The tests were carried out on an industrial and laboratory starching machine. According to the obtained results, the necessity and the improvement of the physical-mechanical properties of cotton and aramid yarns can be determined, both by industrial and laboratory starching. Finer yarn starched by the laboratory starching process achieves greater efficiency in the yarn’s strength and resistance to wear, which indicates the need for starching aramid yarns, especially fineness 16.6 × 2 tex, but also finer ones.

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Ana Kis

Papers

Transcobalamin II deficiency at birth.

Thermal Protective Properties and Breathability of Multilayer Protective Woven Fabrics for Wildland Firefighting

Application of 3D-Woven Fabrics for Packaging Materials for Terminally Sterilized Medical Devices

Justification of Starching Cotton and Aramid Yarns by Industrial and Laboratory Processes