Prepubertal onset of type 2 diabetes in Shashi-Pena syndrome due to ASXL2 mutation.

Type 2 diabetes remains rare in the pediatric population and the majority of cases occur during puberty. A combination of genetic and environmental factors leads to the development of insulin resistance and ß-cell failure. An increased prevalence is recognized in a number of rare genetic disorders such as Alström and Bardet-Biedl syndromes. Recently, a rare neurodevelopmental disorder, Shashi-Pena syndrome due to the dominant negative effect of heterozygous mutations in additional Sex-Combs-Like Genes 2 (ASXL2) has been reported. ASXL2 null mice exhibit glucose intolerance, insulin resistance and lipodystrophy. The regulatory role of ASXL2 in glucose and lipid homeostasis occurs through its interaction with peroxisome proliferator-activated receptor gamma (PPARγ), a gene implicated in the pathogenesis of type 2 diabetes on genome-wide association studies. Thiazolidinediones, used for the treatment of type 2 diabetes, exert their effects as direct agonists of PPARγ. We report the first case of type 2 diabetes in Shashi-Pena syndrome, occurring in an 8-year-old prepubertal boy with no family history. In addition, the proband had dyslipidemia, and fatty infiltration of the liver with elevated transaminases. Mutation of ASXL2 in humans, through its interaction with PPARγ appears to cause a phenotype of insulin resistance, type 2 diabetes, and dyslipidemia. Further reported cases will assist in confirming this association.

Standardised mortality is increased three-fold in a population-based sample of children and adolescents with type 1 diabetes.

There are no type 1 diabetes (T1DM) mortality data on Australian children and limited contemporary data on their international counterparts. Fatalities in children and adolescents (1-17 yr) with T1DM were identified from the Western Australia Children's Diabetes Database between 1987-2011. Seventeen thousand four hundred and fifty-three patient-years of diabetes data were analysed and 13 deaths were confirmed (six male). The overall standardised mortality ratio was 3.1 [95% confidence interval (CI), 1.7-5.3] and was highest in the 10-14 yr age group, at 4.6 (95% CI, 1.5-10.8). Median age at death was 16.4 yr (range 5 to 17.8 yr), and median haemoglobin A1c at death was 10.5% (range 6.7 to >14). Cause of death was attributed to diabetes in 10 (77%) cases. Two patients were found 'dead-in-bed'. All diabetes-related deaths in subjects with known T1DM occurred outside the hospital setting.

School-based management of type 1 diabetes in the Republic of Ireland: a cross-sectional mixed-methods analysis.

BACKGROUND: Qualitative research regarding the experience of diabetes self-care management in schools is underrepresented in published literature. In addition, there are methodologic limitations in some of the existing studies. AIMS: To investigate experiences of school-based diabetes self-care management in children and adolescents with type 1 diabetes. METHODS: Cross-sectional mixed-methods questionnaire survey. Sentiment analysis was undertaken of free-text responses by primary caregivers of young children and adolescents or adolescents themselves in relation to experiences regarding school-based support for self-care. Statements were rated on a 5-point Likert scale from strongly negative (1) to strongly positive (5). Responses were also grouped using thematic analysis. A quantitative analysis of the similarities and differences in responses between primary and secondary school students was undertaken. RESULTS: Text responses for analysis were present in 273 (65%) primary and 226 (56%) secondary school questionnaires. Sentiment analysis yielded mean scores of 3.5 and 2.8 for primary and secondary students, respectively. Three major themes were identified in the statements, namely attitude, education/knowledge, and resources. Scores within each theme were significantly higher for primary compared to secondary students. Attitude scored highest and education/knowledge scored lowest in both groups. Comments in relation to resources were significantly more frequent in primary school questionnaires, and comments regarding education and knowledge were more commonplace in secondary school responses. CONCLUSION: Our findings suggest that experiences regarding self-care management of type 1 diabetes are generally more positive among primary school students. Education and knowledge of school staff should be a particular area of focus in both cohorts.

Spontaneous remission of pendulum swinging thyroid disease in Down syndrome.

Summary: Rare patients who have both thyroid-stimulating hormone (TSH) receptor-stimulating and -blocking antibodies can develop 'pendulum swinging' thyroid dysfunction. A 9-year-old girl with Down syndrome was treated with carbimazole for Graves' disease. After 2 years of treatment, she became profoundly biochemically hypothyroid, and this persisted after carbimazole was discontinued. Low-dose L-thyroxine was commenced. This was subsequently also discontinued as biochemical hyperthyroidism developed. TSH receptor antibody bioassay identified both TSH receptor-stimulating and -blocking antibodies. Mild hyperthyroidism persisted and while consultations regarding definitive treatment were ongoing, medication was not recommenced. Thyroid function normalised spontaneously and she has remained euthyroid for the past 3 years. Previous reports have advised definitive treatment; however, our patient developed spontaneous remission which has been prolonged and definitive therapies have been avoided. It is not yet known how commonly this particular phenomenon occurs. Learning points: Rare patients who have both TSH receptor-stimulating and -blocking antibodies can switch between hyperthyroidism and hypothyroidism or vice versa during treatment with antithyroid drugs or thyroxine. Metamorphic thyroid autoimmunity is more common in Down syndrome. Switching between hyperthyroidism and hypothyroidism and back again is less commonly reported. Definitive treatment such as radioactive iodine or thyroidectomy are usually recommended. Prolonged remission was achieved off all medication, without recourse to definitive treatments.

Adolescent onset of autoimmune polyglandular syndrome type 2.

An adolescent female was evaluated for fatigue, anorexia and unintentional weight loss of 7 kg. Initial investigations revealed subclinical autoimmune thyroid dysfunction, which progressed to overt hypothyroidism necessitating thyroxine replacement. She had entered early puberty, but this did not appear to be progressing. A high index of suspicion for coexisting endocrinopathies resulted in a diagnosis of Addison's disease and consequently autoimmune polyglandular syndrome type 2 (Schmidt syndrome). While basal gonadotropins were normal, anti-Mullerian hormone was low and ovarian autoantibodies were positive, consistent with preclinical premature ovarian failure. Glucocorticoid and mineralocorticoid replacement were instituted. Puberty progressed and menarche was subsequently attained. Screening for other autoantibodies was undertaken; however, none are positive to date.

Whole exome sequencing based identification of a case of cardiofaciocutaneous syndrome type 3: the benefits of new sequencing technology in children with neurodevelopmental delay.

We report the case of a boy with a prolonged diagnostic workup for global developmental delay alongside feeding difficulties, failure to thrive, pulmonary stenosis and macrocephaly. Following a series of diagnostic tests over the first 25 months of life, whole-exome sequencing was performed which diagnosed cardiofaciocutaenous syndrome type 3.Global developmental delay is a common presentation to general paediatric and community paediatric clinics. This prompts the search for an aetiology to describe the child's constellation of symptoms which often consists of a chromosomal microarray, neuroimaging and investigations for an inborn error of metabolism. With developments in genetic testing such as the reducing cost of clinical exome sequencing or whole-exome sequencing, could these testing strategies offer a more comprehensive first line test?This case not only demonstrates the features of cardiofaciocutaneous syndrome type 3 but the added value of modern genetic technologies in the diagnosis of children with global developmental delay.

Publication of abstracts presented at the Irish Paediatric Association conference.

BACKGROUND: The proportion of abstracts presented at medical conferences that are subsequently published is a potentially useful surrogate for the quality of the material presented. The mean publication percentage for paediatric conference abstracts reported in the literature is 39%. The publication of abstracts presented at the Irish Paediatric Association's (IPA) annual conference have not previously been explored. AIM: To identify the subsequent publication proportion for abstracts presented at the IPA annual conference and to identify factors associated with a higher likelihood of publication. METHODS: As 95% of publications occur within 5 years of conference presentation, abstracts from the 2008 to 2012 IPA conferences were selected for analysis. A PubMed/Medline search was conducted using the author's names and, if required, abstract keywords. For comparability with previous studies, articles were deemed published if they were full journal articles, contained at least one similar author and reported similar outcomes. RESULTS: Over the 5-year study period, 584 IPA abstracts were presented. The percentage of abstracts published was 19.7%. One hundred and fifteen articles were published in 45 different journals; 31 (27%) of these were published in the Irish Medical Journal. The percentage of abstracts published was significantly higher for oral presentations (23% vs. 15%; p = 0.012), university-associated abstracts (31% vs. 16%; p < 0.001) and interventional studies (52% vs. 18%; p < 0.001). On multivariate analysis, only university association and interventional studies remained significantly associated with publication. CONCLUSION: The percentage of IPA abstracts that were published was low when compared internationally. Further analysis is required to explore the reasons underpinning this.

Donor human milk use in neonatal units: practice and opinions in the Republic of Ireland.

BACKGROUND: Over the past decade, where mother's own milk (MOM) is unavailable, the use of donor human milk has become increasingly common in preterm and very low birth weight (VLBW) neonates. Limited literature exists regarding donor human milk practices in neonatal units. AIMS: To examine practices and opinions regarding use of donor human milk in neonatal units in the Republic of Ireland. METHODS: Cross-sectional postal survey of all neonatologists and paediatricians working in each of the 19 neonatal units in the Republic of Ireland. MAIN RESULTS: Eighty-eight paediatricians and neonatologists were surveyed and 44 (50%) replied. Responses were received from 20 (95%) neonatal units, of whom 15 (75%) reported using donor milk. Sixty percent of units had a written donor milk policy however significant variation existed in birth weight and gestational age thresholds for its use. Thirty-eight (86%) of respondents were opposed to the use of donor milk for supplementation of otherwise healthy term neonates. Ten (23%) of respondents believed that supplementation with donor milk compared to formula improves long-term breastfeeding rates. Twenty-two (56%) agreed that the majority of studies supporting the use of donor milk to prevent necrotising enterocolitis in preterm infants were undertaken in the past 15 years. CONCLUSION: This is the first study to evaluate current practices and opinions regarding donor milk use in the Republic of Ireland and highlights the necessity to develop a national guideline of evidence-based best practice.

Cholesterol screening in an at-risk pediatric population.

Elevation of low-density lipoprotein (LDL) cholesterol is a recognized risk factor for premature atherosclerosis and such elevations have their antecedents in the pediatric population. This study evaluated the frequency of elevated LDL cholesterol in children and adolescents (8-18 years) in whom one parent had a history of premature ischemic heart disease (<55 years). Patients had a fasting lipid profile performed and results were classified as normal, borderline/high, or high in accordance with the American Academy of Pediatrics (AAP) guidelines. Fifty-two parents had a total of 97 children and adolescents who were eligible for screening. Ninety-three initially consented and fasting lipid profiles were obtained in 82 (84.5%) children. Prevalences of high and borderline/high LDL cholesterol were (7/82) 8.5% and (17/82) 20.7%, respectively. Screening for hypercholesterolemia in these at-risk children and adolescents is prudent and dietary advice must be offered.