PurposeMutations in POLG, the most common single-gene cause of inherited mitochondrial disease, are diagnostically challenging owing to clinical heterogeneity and overlap between syndromes. We aimed to improve the clinical recognition of POLG-related disorders in the pediatric population.MethodsWe performed a multinational, phenotype: genotype study using patients from three centers, two Norwegian and one from the United Kingdom. Patients with age at onset <12 years and confirmed pathogenic biallelic POLG mutations were considered eligible.ResultsA total of 27 patients were identified with a median age at onset of 11 months (range 0.6-80.4). The majority presented with global developmental delay (n=24/24, 100%), hypotonia (n=22/23, 96%) and faltering growth (n=24/27, 89%). Epilepsy was common, but notably absent in patients with the myocerebrohepatopathy spectrum phenotype. We identified two novel POLG gene mutations.ConclusionOur data suggest that POLG-related disease should be suspected in any child presenting with diffuse neurological symptoms. Full POLG sequencing is recommended since targeted screening may miss mutations. Finally, we simplify the classification of POLG-related disease in children using epilepsy as the crucial defining element; we show that Alpers and myocerebrohepatopathy spectrum follow different outcomes and that they manifest different degrees of respiratory chain dysfunction.

Summary Background Aprepitant (Emend, Merck Sharp & Dohme Ltd, Haarlem, the Netherlands), a neurokinin‐1 receptor antagonist, prevents vomiting in a range of conditions. No data are available on its use in children with cyclical vomiting syndrome (CVS). Aim We investigated the efficacy of aprepitant as prophylactic treatment or acute intervention in CVS children refractory to conventional therapies. Methods Forty‐one children (median age: 8 years) fulfilling NASPGHAN criteria treated acutely (RegA) or prophylactically (RegP) with aprepitant were retrospectively reviewed. Primary outcome was the clinical response (decrease in frequency and intensity of CVS episodes). Secondary outcomes were: number of CVS episodes/year, number of hospital admissions/year, CVS episode duration, number of vomits/h, symptom‐free interval length (days), and school attendance percentage. The follow‐up period was 18–60 months. Results Sixteen children received RegP and 25 RegA. One child on RegP stopped treatment due to severe migraine. At 12‐months on intention‐to‐treat analysis, 13 children on RegP (81%) achieved either complete (3/16, 19%) or partial (10/16, 62%) clinical response. On RegA, 19 children (76%) had either complete (3/25, 12%) or partial (16/25, 64%) response (P = 0.8 vs. RegP). In both RegP and RegA, there was a significant decrease in CVS episodes/year, hospital admission number/year, CVS episode length, number of vomits/h, as well as an increase in symptom‐free interval duration and school attendance percentage. Side effects were reported only in RegP (5/16, 31%) including hiccough (3/16, 19%), asthenia/fatigue (2/16, 12.5%), increased appetite (2/16, 12.5%), mild headache (1/16, 6%) and severe migraine (1/16, 6%). Conclusion Aprepitant appears effective for both acute and prophylactic management of paediatric cyclical vomiting syndrome refractory to conventional therapies.

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Since the online publication of the article, the authors have noted errors with Table 2; this has now been corrected in both the HTML and the PDF.

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IntroductionSmall bowel imaging is an important part of the diagnostic work up in Paediatric IBD both for disease classification and identification of complications. Opinion varies as to the modality and timing of small bowel imaging and MRI enteroclysis has become widely available surpassing Barium studies. The utility of Ultrasound abdomen (USS) in small bowel disease has been poorly evaluated in early onset IBD.Aimsand objectives We aimed to evaluate the adequacy of USS in detection of small bowel disease at the initial work up of early onset IBD according to the Porto Criteria. We also compared the findings on MRIE to recent small bowel USS, where available, and to historical findings on USS at presentation in a known cohort of patients with early onset Crohn’s disease.Materials and methodsData from patients with an established diagnosis of Crohn’s disease that had MRI small bowel as part of disease reassessment during a two year period (2013–2014) was collected. Findings on MRIE were compared with USS data done at the beginning of illness or concurrently for disease location, behaviour, and presence/absence of complications.Results33 patients with MRI small bowel study were eligible. The median age at initial diagnosis was 11.2 years. All had USS small bowel at the time of diagnosis. The median time duration to MRIE (as part of disease reassessment) was 31 months. 14/33 patients had abnormalities on MRI small bowel that were previously found on the initial diagnostic ultrasound. 4/28 of patients who had normal initial ultrasound had MRI abnormalities either indicative of small bowel disease progression or the limitation of Ultrasound. Of the 33 patients who had MRI small bowel for disease re- evaluation, 9 patients had a preceding ultrasound within 3 months. The concurrent USS were abnormal in 6 patients and correlated with MRIE findings.ConclusionUSS small bowel in the hands of a trained paediatric radiologist is useful in detecting small bowel disease and has high sensitivity as a diagnostic tool. However MRIE supersedes USS in accurate topographic mapping, definition of disease and complications. Despite the absence of small bowel disease at diagnosis, a low threshold is required for reassessing small bowel disease in early onset Crohn’s disease.