No abstract

The relatively rare proximal microdeletion of 17q12 (including deletion of the HNF1B gene) is associated with the renal cysts and diabetes syndrome. Recent reports have suggested that there may also be an association between this microdeletion and learning difficulties/autism. This case report describes one of only a few reported families segregating the 17q12 microdeletion, but which highlights the nonpenetrance and variable expressivity of multiple features of this condition.

Background: The role of vitamin D and omega-3 long chain polyunsaturated fatty acids (omega-3 LCPUFA) in improving core symptoms of autism spectrum disorder (ASD) in children has been investigated by a few randomised controlled trials and the results are mixed and inconclusive. The response to treatment with these nutrients is heterogenous and may be influenced by inflammatory state. As an exploratory analysis, we investigated whether inflammatory state would modulate the effect of these nutrients on core symptoms of ASD. Methods: Seventy-three New Zealand children with ASD (2.5-8.0 years) completed a 12-month randomised, double-blind, placebo-controlled trial of vitamin D (VID, 2000 IU/day), omega-3 LCPUFA; (OM, 722 mg/day docosahexaenoic acid), or both (VIDOM). Non-fasting baseline plasma interleukin-1β (IL-1β) was available for 67 children (VID = 15, OM = 21, VIDOM = 15, placebo = 16). Children were categorised as having undetectable/normal IL-1β (<3.2 pg/ml, n = 15) or elevated IL-1β (≥3.2 pg/mL, n = 52). The Social Responsiveness Scale (SRS) questionnaire was used to assess core symptoms of ASD (baseline, 12-month). Mixed model repeated measure analyses (including all children or only children with elevated IL-1β) were used. Results: We found evidence for an interaction between baseline IL-1β and treatment response for SRS-total, SRS-social communicative functioning, SRS-awareness and SRS-communication (all P interaction < 0.10). When all children were included in the analysis, two outcome comparisons (treatments vs. placebo) showed greater improvements: VID, no effect (all P > 0.10); OM and VIDOM (P = 0.01) for SRS-awareness. When only children with elevated IL-1β were included, five outcomes showed greater improvements: OM (P = 0.01) for SRS-total; OM (P = 0.03) for SRS-social communicative Nutrients 2020, 12, 661 2 of 17 functioning; VID (P = 0.01), OM (P = 0.003) and VIDOM (P = 0.01) for SRS-awareness. Conclusion: Inflammatory state may have modulated responses to vitamin D and omega-3 LCPUFA intervention in children with ASD, suggesting children with elevated inflammation may benefit more from daily vitamin D and omega-3 LCPUFA supplementation.

BackgroundThere is strong mechanistic evidence to suggest that vitamin D and omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFAs), specifically docosahexaenoic acid (DHA), have the potential to significantly improve the symptoms of autism spectrum disorder (ASD). However, there are no trials that have measured the effect of both vitamin D and n-3 LCPUFA supplementation on autism severity symptoms. The objective of this 2 × 2 factorial trial is to investigate the effect of vitamin D, n-3 LCPUFAs or a combination of both on core symptoms of ASD.Methods/designChildren with ASD living in New Zealand (n = 168 children) will be randomised to one of four treatments daily: vitamin D (2000 IU), n-3 LCPUFAs (722 mg DHA), vitamin D (2000 IU) + n-3 LCPUFAs (722 mg DHA) or placebo for 12 months. All researchers, participants and their caregivers will be blinded until the data analysis is completed, and randomisation of the active/placebo capsules and allocation will be fully concealed from all mentioned parties. The primary outcome measures are the change in social-communicative functioning, sensory processing issues and problem behaviours between baseline and 12 months. A secondary outcome measure is the effect on gastrointestinal symptoms. Baseline data will be used to assess and correct basic nutritional deficiencies prior to treatment allocation. For safety measures, serum 25-hydroxyvitamin D 25(OH)D and calcium will be monitored at baseline, 6 and 12 months, and weekly compliance and gastrointestinal symptom diaries will be completed by caregivers throughout the study period.DiscussionTo our knowledge there are no randomised controlled trials assessing the effects of both vitamin D and DHA supplementation on core symptoms of ASD. If it is shown that either vitamin D, DHA or both are effective, the trial would reveal a non-invasive approach to managing ASD symptoms.Trial registrationAustralian New Zealand Clinical Trial Registry, ACTRN12615000144516. Registered on 16 February 2015.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-016-1428-8) contains supplementary material, which is available to authorized users.