Case Report: Extended Clinical Spectrum of the Neonatal Diabetes With Congenital Hypothyroidism Syndrome

BackgroundNeonatal diabetes with congenital hypothyroidism (NDH) syndrome is a rare condition caused by homozygous or compound heterozygous mutations in the GLI-similar 3 coding gene GLIS3. Almost 20 patients have been reported to date, with significant phenotypic variability.Case presentationWe describe a boy with a homozygous deletion (exons 5-9) in the GLIS3 gene, who presents novel clinical aspects not reported previously. In addition to neonatal diabetes, congenital hypothyroidism and other known multi-organ manifestations such as cholestasis and renal cysts, he suffered from hyporegenerative anemia during the first four months of life and presents megalocornea in the absence of elevated intraocular pressure. Compensation of partial exocrine pancreatic insufficiency and deficiencies in antioxidative vitamins seemed to have exerted marked beneficial impact on several disease symptoms including cholestasis and TSH resistance, although a causal relation is difficult to prove. Considering reports on persistent fetal hemoglobin detected in a few children with GLIS3 mutations, the transient anemia seen in our patient may represent a further symptom associated with either the GLIS3 defect itself or, secondarily, micronutrient deficiency related to exocrine pancreatic deficiency or cholestasis.ConclusionsOur report expands the phenotypic spectrum of patients with GLIS3 mutations and adds important information on the clinical course, highlighting the possible beneficial effects of pancreatic enzyme and antioxidative vitamin substitutions on characteristic NDH syndrome manifestations such as TSH resistance and cholestasis. We recommend to carefully screen infants with GLIS3 mutations for subtle biochemical signs of partial exocrine pancreatic deficiency or to discuss exploratory administration of pancreatic enzymes and antioxidative vitamins, even in case of good weight gain and fecal elastase concentrations in the low-to-normal range.

86 SIMPLE METHOD FOR EMULSIFICATION OF LIPOPHILIC NUTRIENTS THAT AFFECT PRE-IMPLANTATION DEVELOPMENT OF BOVINE EMBRYOS IN VITRO

In order to investigate the effects of bioactive lipophilic nutrients on mammalian pre-implantation embryos in vitro, amphipathic vehicles are commonly used to dissolve the lipophilic substances into culture media. However, easy emulsification of these nutrients would facilitate medium preparation. We report here a simple method for emulsification of lipophilic nutrients that affect bovine pre-implantation embryonic development in vitro. We investigated the effects of emulsified oleic acid (OA) or a mixture of antioxidative vitamins – vitamin E (VE) and β-carotene (BC). Polyglyceryl-10 laurate (P10L) was used as an emulsifier and was dissolved in sterile water at 5.05% (wt/wt) in glass vials. One percent (wt/wt) of OA or a mixture of VE (α-tocopherol) and BC (VE : BC = 1000 : 1 wt/wt) was added into the vial and mixed by using a magnetic stirrer. After first exhibiting white turbidity, the solution became transparent and stabilised, indicating stable emulsification. The emulsified OA and VE+BC were designated as emOA and emVEBC, respectively. Cumulus-enclosed oocytes obtained from abattoir bovine ovaries were in vitro-matured (IVM) for 22 h in modified synthetic oviduct fluid (mSOF) supplemented with 10% (vol/vol) fetal calf serum and 0.2 IU mL–1 FSH. After IVM, the oocytes were subjected to IVF with Percoll gradient-selected sperm from a single bull in an mSOF-based medium for 20 h. After IVF, presumptive zygotes were freed from the cumulus cells and cultured in mSOF. On Day 3 (IVF = Day 0), embryos that had developed to the 8-cell stage or more (≥8-cell) were subsequently cultured in medium supplemented with 0.05% (vol/vol) of emOA or emVEBC. Blastocyst development from ≥8-cell embryos was assessed on Day 8. In the case of no-additive control and emVEBC, the hatching rate was also assessed on Day 10. All the cultures were performed at 38.5°C under 5% CO2, 5% O2, and 90% N2 and replicated 4 times with ~18 embryos per group per replicate. The development data were statistically analysed by the general linear model. The blastocyst rate in the emOA group (36.4%) was significantly (P < 0.05) lower than that in the no-additive control (54.1%). The blastocyst rate in the emVEBC group (53.9%) was similar to that in the control; however, the hatching rate was significantly higher in the emVEBC group (22.6%) than in the control (9.2%). These data suggest that emulsification of lipophilic nutrients with P10L is an easy method to allow their addition into culture media for investigating their favourable (e.g. antioxidative vitamins) or inhibitory (e.g. OA) effects on pre-implantation development in vitro.

Adverse effects of antioxidative vitamins

High doses of synthetic antioxidative vitamins: A, E, C and β-carotene are often used on long-term basis in numerous preventive and therapeutic medical applications. Instead of expected health effects, the use of those vitamins may however lead to cases of hypervitaminosis and even to intoxication. The article points out main principles of safety which are to be observed during supplementation with antioxidative vitamins. Toxic effects resulting from erroneous administration of high doses of those substances on organs and systems of the organism are also discussed. Attention is drawn to interactions of antioxidative vitamins with concomitantly used drugs, as well as intensification of adverse effects caused by various exogenous chemical factors. Moreover, the article presents the evaluation of supplementation with these vitamins, which was performed in large studies.

The effect of addition of ß-carotene, vitamins C and E in feed mixture enriched with CLA on sensory traits and oxidative status of pork meat

There is some concern that meat and eating quality can suffered as a result of dietary CLA supplementation through the influence on fatty acids metabolism and it content in meat. CLA addition to pigs’ diet requires simultaneous addition of antioxidative vitamins’ taking part in stabilization of double bonds of CLA inbuilt in phospholipids complex of cell membrane (Livisay et al., 2000).