Differential diagnosis between MODY3 and early-onset type 2 diabetes remains difficult. Whether the proposed model will improve the pick-up rate of MODY3 diagnosis needs to be confirmed in independent populations.

Aims/hypothesis Anti-zinc transporter (ZnT)8 autoantibodies are commonly detected in type 1 diabetic patients. We hypothesized that ZnT8 is also recognized by CD8+ T cells and aimed at identifying HLA-A2 (A*02:01)-restricted epitope targets. Methods Candidate epitopes were selected by ZnT8 plasmid DNA immunization of HLA-A2/DQ8-transgenic mice and tested for T-cell recognition in peripheral blood mononuclear cells of type 1 diabetic, type 2 diabetic and healthy subjects by IFN-γ enzyme-linked immunospot. Results Caucasian HLA-A2+ type 1 diabetic patients, both adults (83%) and children (60%),displayed ZnT8-reactive CD8+ T cells which recognized a single ZnT8186–194 (VAANIVLTV) epitope. This ZnT8186–194-reactive fraction accounted for 50–53% of total ZnT8-specific CD8+ T cells. Another ZnT8153–161 (VVTGVLVYL) sequence was recognized in 20–25% of type 1 diabetic adults and children, respectively. Both epitopes were type 1 diabetes-specific, being marginally recognized by type 2 diabetic and healthy subjects (7–12% for ZnT8186–194 and 0% for ZnT8153–161). Conclusions/interpretation ZnT8-reactive CD8+ T cells are predominantly directed against the ZnT8186–194 epitope and are detected in a majority of type 1 diabetic patients. The exceptional immunodominance of ZnT8186–194 may point to common environmental triggers precipitating beta-cell autoimmunity.

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ObjectivesKetamine, an N-methyl-D-aspartate receptor antagonist, is effective at relieving adult cancer pain, although there have been very few reports to date regarding its use in children and in adolescents and young adults (AYA). This study assessed the efficacy, safety and opioid-sparing effects of low doses of ketamine added to opioid analgesics to alleviate persistent cancer pain.MethodsThis prospective, multicentre, observational trial collected data regarding demographics, pain characteristics, pain score assessment within the first 48 hours of ketamine administration, tolerance and satisfaction from 38 patients aged 2–24 years prescribed with ketamine as an adjuvant antalgic for refractory cancer pain in 10 French paediatric oncology centres.ResultsThe mean visual analogue scale pain score decreased from 6.7 to 4.3 out of 10 (n=39, p<0.001) from day 1 to day 3 and by at least 2 points in 56% of the patients (n=22) 48 hours after initiation of ketamine. Nine patients experienced poor tolerance (≥2 side effects), all with infusion rates lower than 0.05 mg/kg/hour. None had limiting toxicities. An opioid-sparing effect was highlighted in four patients. Fifty-four per cent of the prescribers and 47% of the patients found the addition of ketamine ‘very helpful’.ConclusionsLow doses of ketamine as an adjuvant to opioids significantly reduced the intensity of pain in half of the study population. A tendency towards better pain control is shown, although a lack of statistical power somewhat limits our conclusions, especially in children. Nevertheless, ketamine may be a useful option for improving the treatment of refractory pain in children and AYA with cancer.

Neuroblastoma (NB), an embryonic tumour arising from neural crest cells, is the most common malignancy among infants. The aetiology of NB is largely unknown. We conducted a pooled analysis to explore whether there is an association between NB and preconception and perinatal factors using data from two French national population-based case-control studies. The mothers of 357 NB cases and 1783 controls younger than 6 years, frequency-matched by age and gender, responded to a telephone interview that focused on demographic, socioeconomic and perinatal characteristics, childhood environment, life-style and maternal reproductive history. Unconditional logistic regression was used to estimate pooled odds ratios and 95% confidence intervals. After controlling for matching variables, study of origin and potential confounders, being born either small (OR 1.4 95% CI 1.0-2.0) or large (OR 1.5 95% CI 1.1-2.2) for gestational age and, among children younger than 18 months, having congenital malformations (OR 3.6 95% CI 1.3-8.9), were significantly associated with NB. Inverse associations were observed with breastfeeding (OR 0.7 95% CI 0.5-1.0) and maternal use of any supplements containing folic acid, vitamins or minerals (OR 0.5 95% CI 0.3-0.9) during the preconception period. Our findings reinforce the hypothesis that fetal growth anomalies and congenital malformations may be associated with an increased risk of NB. Further investigations are needed in order to clarify the role of folic acid supplementation and breastfeeding, given their potential importance in NB prevention.

SUMMARY We present the first report of primary hyperaldosteronism in childhood due to unilateral macronodular hyperplasia. A 10-year-old white boy with severe hypertension (150/100 mm Hg), hypokalemia (1.4 mEq/liter), and suppressed plasma renin activity (PRA) (< 0.1 ng/ml/hr) demonstrated fixed PRA and aldosterone (aldo) levels that did not change with alteration of dietary sodium. The paradoxical decrease in serum aldo on assumption of upright posture suggested a tumor. Prolonged ACTH administration produced a continuous rise in blood pressure, but a transient rise in aldo. A minimal decrease in urinary aldo during dexamethasone administration was noted, excluding dexamethasone-suppressible hyperaldosteronism. Blood pressure normalized with spironolactone. Computerized transaxial tomography, iodocholesterol scanning, and adrenal venography were not diagnostic of a discrete adrenal lesion. Although hyperplasia is more common than an adenoma as a cause of hyperaldosteronism in childhood, a tumor was predicted, since adrenal vein hormone sampling with ACTH stimulation lateralized aldosterone secretion unequivocally to the left adrenal gland. However, left adrenalectomy revealed macronodular hyperplasia. Postoperatively, there was reversal of hypertension, hypokalemia, and hyperaldosteronism. Thus, in childhood, unilateral hypersecretion of aldosterone may result from nodular hyperplasia, rather than a discrete adenoma. signs include hypertension, suppressed plasma renin activity, hypokalemia, and polyuria. A substantial number of the children had evidence of ophthalmologic, cardiac, and neurologic abnormalities. We report herein metabolic and diagnostic studies in a 10-year-old boy with primary hyperaldosteronism caused by excess aldosterone secretion due to unilateral macronodular hyperplasia. Unilateral adrenalectomy resulted in normalization of blood pressure, and reversal of hypokalemia and hyperaldosteronism. Postoperatively there was slow recovery of the renin secreting system and of the response of the glomerulosa in the remaining adrenal gland to renin-angiotensin stimulation; this excluded bilateral adrenal hyperplasia as the cause of the hyperaldosteronism. Case ReportThe patient, a 10-year-old white boy, was in excellent health until 2 months prior to evaluation when he had a generalized seizure. Blood pressure was noted to be 150/100 mm Hg. Serum chemistries revealed: Na

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Aims To assess if systematic fundus screening according to an 'intensive' schedule alters ocular outcome and to propose fundus screening schedule guidelines for children related to a retinoblastoma patient.