RESUMEN
AIMS: Islet autoantibody screening of infants and young children in the Northern Hemisphere, together with semi-annual metabolic monitoring, is associated with a lower risk of ketoacidosis (DKA) and improved glucose control after diagnosis of clinical (stage 3) type 1 diabetes (T1D). We aimed to determine if similar benefits applied to older Australians and New Zealanders monitored less rigorously. METHODS: DKA occurrence and metabolic control were compared between T1D relatives screened and monitored for T1D and unscreened individuals diagnosed in the general population, ascertained from the Australasian Diabetes Data Network. RESULTS: Between 2005 and 2019, 17,105 relatives (mean (SD) age 15.7 (10.8) years; 52% female) were screened for autoantibodies against insulin, glutamic acid decarboxylase, and insulinoma-associated protein 2. Of these, 652 screened positive to a single and 306 to multiple autoantibody specificities, of whom 201 and 215, respectively, underwent metabolic monitoring. Of 178 relatives diagnosed with stage 3 T1D, 9 (5%) had DKA, 7 of whom had not undertaken metabolic monitoring. The frequency of DKA in the general population was 31%. After correction for age, sex and T1D family history, the frequency of DKA in screened relatives was >80% lower than in the general population. HbA1c and insulin requirements following diagnosis were also lower in screened relatives, consistent with greater beta cell reserve. CONCLUSIONS: T1D autoantibody screening and metabolic monitoring of older children and young adults in Australia and New Zealand, by enabling pre-clinical diagnosis when beta cell reserve is greater, confers protection from DKA. These clinical benefits support ongoing efforts to increase screening activity in the region and should facilitate the application of emerging immunotherapies.
Asunto(s)
Diabetes Mellitus Tipo 1 , Cetoacidosis Diabética , Cetosis , Niño , Lactante , Humanos , Femenino , Adolescente , Preescolar , Masculino , Diabetes Mellitus Tipo 1/complicaciones , Nueva Zelanda , Cetoacidosis Diabética/epidemiología , Australia , Insulina/uso terapéutico , AutoanticuerposRESUMEN
Individuals with Prader-Willi syndrome (PWS) often have excessive daytime sleepiness and emotional/behavioral disturbances. The objective of this study was to examine whether daytime sleepiness was associated with these emotional/behavioral problems, independent of nighttime sleep-disordered breathing, or the duration of sleep. Caregivers of individuals with PWS (aged 3 to 25 years) completed the Pediatric Sleep Questionnaire (PSQ), Epworth Sleepiness Scale for Children and Adolescents (ESS-CHAD), and the parent version of the Developmental Behavior Checklist (DBC-P). Sleep adequacy was adjusted for age by computing sleep duration against age-specific recommendations. The associations between ESS-CHAD and the total DBC and its subscale scores were evaluated by linear regression, adjusted for sleep-related breathing difficulties, sleep adequacy, and body mass index (BMI). There were 54 responses for individuals with PWS (including 22 males) aged 4.4-24.0 (mean 12.5) years. Daytime sleepiness predicted a substantial proportion of the variance in total DBC-P scores in the unadjusted model (28%; ß = 0.028; p < 0.001) and when adjusted for sleep adequacy, BMI, and sleep-related breathing difficulties (29%; ß = 0.023; p = 0.007). This relationship was not moderated by BMI Z-scores, but the relationship was more prominent for children younger than 12 years than for children older than 12 years.Conclusions: These findings provide preliminary novel evidence that daytime sleepiness may drive the expression of emotional/behavioral disturbances, and should be explored as a potential modifiable risk factor for these disturbances in PWS, particularly pre-adolescent children.
Asunto(s)
Trastornos de Somnolencia Excesiva , Síndrome de Prader-Willi , Problema de Conducta , Adolescente , Niño , Trastornos de Somnolencia Excesiva/complicaciones , Emociones , Humanos , Masculino , Síndrome de Prader-Willi/complicaciones , SueñoRESUMEN
Platelet-neutrophil aggregates (PNAs) facilitate neutrophil activation and migration and could underpin the recruitment of neutrophils to the pancreas during type 1 diabetes (T1D) pathogenesis. PNAs, measured by flow cytometry, were significantly elevated in the circulation of autoantibody-positive (Aab+) children and new-onset T1D children, as well as in pre-T1D (at 4 weeks and 10-12 weeks) and T1D-onset NOD mice, compared with relevant controls, and PNAs were characterized by activated P-selectin+ platelets. PNAs were similarly increased in pre-T1D and T1D-onset NOD isolated islets/insulitis, and immunofluorescence staining revealed increased islet-associated neutrophil extracellular trap (NET) products (myeloperoxidase [MPO] and citrullinated histones [CitH3]) in NOD pancreata. In vitro, cell-free histones and NETs induced islet cell damage, which was prevented by the small polyanionic drug methyl cellobiose sulfate (mCBS) that binds to histones and neutralizes their pathological effects. Elevated circulating PNAs could, therefore, act as an innate immune and pathogenic biomarker of T1D autoimmunity. Platelet hyperreactivity within PNAs appears to represent a previously unrecognized hematological abnormality that precedes T1D onset. In summary, PNAs could contribute to the pathogenesis of T1D and potentially function as a pre-T1D diagnostic.
Asunto(s)
Plaquetas/inmunología , Agregación Celular/inmunología , Diabetes Mellitus Tipo 1 , Trampas Extracelulares , Neutrófilos/inmunología , Páncreas , Animales , Autoanticuerpos/sangre , Niño , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/inmunología , Diagnóstico Precoz , Trampas Extracelulares/diagnóstico por imagen , Trampas Extracelulares/inmunología , Femenino , Técnica del Anticuerpo Fluorescente/métodos , Humanos , Masculino , Ratones , Ratones Endogámicos NOD , Activación Neutrófila/inmunología , Selectina-P/metabolismo , Páncreas/inmunología , Páncreas/patologíaRESUMEN
OBJECTIVE: Continuous glucose monitoring (CGM) is increasingly used in type 1 diabetes management; however, funding models vary. This study determined the uptake rate and glycemic outcomes following a change in national health policy to introduce universal subsidized CGM funding for people with type 1 diabetes aged <21 years. RESEARCH DESIGN AND METHODS: Longitudinal data from 12 months before the subsidy until 24 months after were analyzed. Measures and outcomes included age, diabetes duration, HbA1c, episodes of diabetic ketoacidosis and severe hypoglycemia, insulin regimen, CGM uptake, and percentage CGM use. Two data sources were used: the Australasian Diabetes Database Network (ADDN) registry (a prospective diabetes database) and the National Diabetes Service Scheme (NDSS) registry that includes almost all individuals with type 1 diabetes nationally. RESULTS: CGM uptake increased from 5% presubsidy to 79% after 2 years. After CGM introduction, the odds ratio (OR) of achieving the HbA1c target of <7.0% improved at 12 months (OR 2.5, P < 0.001) and was maintained at 24 months (OR 2.3, P < 0.001). The OR for suboptimal glycemic control (HbA1c ≥9.0%) decreased to 0.34 (P < 0.001) at 24 months. Of CGM users, 65% used CGM >75% of time, and had a lower HbA1c at 24 months compared with those with usage <25% (7.8 ± 1.3% vs. 8.6 ± 1.8%, respectively, P < 0.001). Diabetic ketoacidosis was also reduced in this group (incidence rate ratio 0.49, 95% CI 0.33-0.74, P < 0.001). CONCLUSIONS: Following the national subsidy, CGM use was high and associated with sustained improvement in glycemic control. This information will inform economic analyses and future policy and serve as a model of evaluation diabetes technologies.
Asunto(s)
Diabetes Mellitus Tipo 1 , Adolescente , Adulto , Glucemia , Automonitorización de la Glucosa Sanguínea , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Hemoglobina Glucada/análisis , Humanos , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Estudios Prospectivos , Adulto JovenRESUMEN
Prader-Willi syndrome (PWS) is a rare genetic disorder characterised by neurodevelopmental delays, hyperphagia, difficulties with social communication and challenging behaviours. Individuals require intensive supervision from caregivers which may negatively affect caregiver quality of life. This study used data collected in the Australasian PWS Registry (n = 50, mean age 11.2 years) to evaluate associations between child behaviours and caregiver mental well-being. Symptoms of sleep-related breathing disorder, child depression and social difficulties were associated with poorer caregiver mental and physical well-being. Growth hormone therapy use was associated with better caregiver mental and physical well-being. Optimising management of problematic behaviours and sleep disturbances have the potential to support caregivers who are the most vital network of support for individuals affected by PWS.
Asunto(s)
Trastorno del Espectro Autista , Síndrome de Prader-Willi , Trastornos del Sueño-Vigilia , Cuidadores , Niño , Humanos , Hiperfagia , Síndrome de Prader-Willi/genética , Calidad de Vida , SueñoRESUMEN
AIM: In children with Prader-Willi syndrome (PWS), growth hormone (GH) improves height and body composition; however, may be associated with worsening sleep-disordered breathing (SDB). Some studies have reported less SDB after GH initiation, but follow-up with polysomnography is still advised in most clinical guidelines. METHODS: This retrospective, multicentre study, included children with PWS treated with GH at seven PWS treatment centres in Australia over the last 18 years. A paired analysis comparing polysomnographic measures of central and obstructive SDB in the same child, before and after GH initiation was performed with Wilcoxon signed-rank test. The proportion of children who developed moderate/severe obstructive sleep apnoea (OSA) was calculated with their binomial confidence intervals. RESULTS: We included 112 patients with available paired data. The median age at start of GH was 1.9 years (range 0.1-13.5 years). Median obstructive apnoea hypopnoea index (AHI) at baseline was 0.43/h (range 0-32.9); 35% had an obstructive AHI above 1.0/h. Follow-up polysomnography within 2 years after the start of GH was available in 94 children who did not receive OSA treatment. After GH initiation, there was no change in central AHI. The median obstructive AHI did not increase significantly (P = 0.13), but 12 children (13%, CI95% 7-21%) developed moderate/severe OSA, with clinical management implications. CONCLUSIONS: Our findings of a worsening of OSA severity in 13% of children with PWS support current advice to perform polysomnography after GH initiation. Early identification of worsening OSA may prevent severe sequelae in a subgroup of children.
Asunto(s)
Síndrome de Prader-Willi , Síndromes de la Apnea del Sueño , Adolescente , Australia/epidemiología , Niño , Preescolar , Hormona del Crecimiento/uso terapéutico , Humanos , Lactante , Síndrome de Prader-Willi/complicaciones , Síndrome de Prader-Willi/tratamiento farmacológico , Estudios Retrospectivos , Síndromes de la Apnea del Sueño/complicaciones , Síndromes de la Apnea del Sueño/tratamiento farmacológicoRESUMEN
Objective: To explore the experiences of young people with type 1 diabetes mellitus (T1DM) and their parents in accessing integrated family-centred care in the Australian Capital Territory during the COVID-19 pandemic. Methods and analysis: This is a pragmatic, qualitative descriptive study for which we conducted semistructured interviews with 11 young people with T1DM aged 12-16 years and 10 of their parents who attended an outpatient diabetes service in Canberra, Australia. Thematic analysis was conducted in accordance with the methods outlined by Braun and Clarke. Results: Three themes were identified: feeling vulnerable, new ways of accessing care and trust in the interdisciplinary diabetes healthcare team. Participants believed having T1DM made them more vulnerable to poor outcomes if they contracted COVID-19, resulting in avoidance of face-to-face care. Telephone consultations offered a convenient and contact-free way to undertake 3-monthly reviews. The greatest difference between telephone and face-to-face consultations was not having access to the whole interdisciplinary diabetes support team at one appointment, physical examination and haemoglobin A1c testing during telehealth consultations. Participants trusted that clinicians would arrange face-to-face meetings if required. Some felt a video option might be better than telephone, reflecting in part the need for more training in communication skills for remote consultations. Conclusion: Young people with T1DM and their parents require collaborative care and contact with multiple healthcare professionals to facilitate self-management and glycaemic control. While telephone consultations offered convenient, safe, contact-free access to healthcare professionals during the COVID-19 pandemic, the added value of video consultations and facilitating access to the whole interdisciplinary diabetes support team need to be considered in future clinical implementation of telehealth.
RESUMEN
In 2016, a global consensus on the prevention, diagnosis and management of nutritional rickets was published. The bone and mineral working group of the Australasian Paediatric Endocrine Group provides a summary and highlights differences to previous Australian and New Zealand (ANZ) guidelines on vitamin D deficiency and their implications for clinicians. Key points are: (i) The International Consensus document is focused on nutritional rickets, whereas the ANZ guidelines were focused on vitamin D deficiency. (ii) Definitions for the interpretation of 25-hydroxy vitamin D (25OHD) levels do not differ between statements. (iii) The global consensus recommends that routine 25OHD screening should not be performed in healthy children and recommendations for vitamin D supplementation are not based solely on 25OHD levels. The Australasian Paediatric Endocrine Group bone and mineral working group supports that screening for vitamin D deficiency should be restricted to populations at risk. (iv) Recommendations from the global consensus for vitamin D dosages for the therapy of nutritional rickets (diagnosed based on history, physical examination, biochemical testing and a confirmation by X-rays) are higher than in ANZ publications. (v) The global consensus recommends the implementation of public health strategies such as universal supplementation with vitamin D from birth to 1 year of age and food fortification. We conclude that updated global recommendations for therapy of nutritional rickets complement previously published position statements for Australia and New Zealand. Screening, management and the implementation of public health strategies need to be further explored for Australia.
Asunto(s)
Raquitismo , Deficiencia de Vitamina D , Australia , Niño , Consenso , Humanos , Nueva Zelanda , Raquitismo/diagnóstico , Raquitismo/tratamiento farmacológico , Raquitismo/prevención & control , Vitamina D/uso terapéutico , Deficiencia de Vitamina D/diagnóstico , Deficiencia de Vitamina D/tratamiento farmacológico , Deficiencia de Vitamina D/prevención & controlRESUMEN
OBJECTIVE: To determine the incidence of childhood onset type 1 diabetes in Australia from 2002 to 2017, and analyze incidence rate trends by calendar year, sex, and age at diagnosis. RESEARCH DESIGN AND METHODS: Children newly diagnosed with type 1 diabetes aged <15 years between 2002 and 2017 were identified from the National Diabetes Register, estimated to be ~99% complete. Data were obtained for diagnosis year, sex, age, and residential State/Territory at time of diagnosis. Population estimates by year, sex, single year of age, and State/Territory were obtained from the Australian Bureau of Statistics and Poisson regression used to examine incidence and trends by calendar year, sex, and age group at diagnosis. RESULTS: Between 2002 and 2017, there were 16 783 newly diagnosed cases of type 1 diabetes in children aged < 15 years (8684 boys: 8099 girls), giving a mean incidence of 25.0/1 00 000 person years (95%CI: 24.6, 25.4). A sinusoidal pattern in the incidence rate trend was observed with 5-yearly cycles providing the best model fit. No significant difference was observed in boys compared to girls (IRR 0.98 [95%CI: 0.95, 1.01]). Compared to 0 to 4 year olds, the mean incidence was 75% higher in 5 to 9 year olds, and 224% higher in 10 to 14 year olds. A decreasing incidence rate trend was observed in 0 to 4 year old boys and girls. CONCLUSIONS: This study reports updated incidence and incidence rate trends in children and adolescents diagnosed with type 1 diabetes in Australia. A cyclical pattern in incidence trend persists, with an overall decreasing trend observed only in the youngest age group.
Asunto(s)
Diabetes Mellitus Tipo 1/epidemiología , Adolescente , Edad de Inicio , Australia/epidemiología , Niño , Preescolar , Diabetes Mellitus Tipo 1/historia , Femenino , Historia del Siglo XXI , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Sistema de RegistrosRESUMEN
Type 1 diabetes (T1D) results from autoimmune destruction of insulin-producing beta cells in pancreatic islets. The degradation of the glycosaminoglycan heparan sulfate (HS) by the endo-ß-D-glycosidase heparanase plays a critical role in multiple stages of the disease process. Heparanase aids (i) migration of inflammatory leukocytes from the vasculature to the islets, (ii) intra-islet invasion by insulitis leukocytes, and (iii) selective destruction of beta cells. These disease stages are marked by the solubilization of HS in the subendothelial basement membrane (BM), HS breakdown in the peri-islet BM, and the degradation of HS inside beta cells, respectively. Significantly, healthy islet beta cells are enriched in highly sulfated HS which is essential for their viability, protection from damage by reactive oxygen species (ROS), beta cell function and differentiation. Consequently, mouse and human beta cells but not glucagon-producing alpha cells (which contain less-sulfated HS) are exquisitely vulnerable to heparanase-mediated damage. In vitro, the death of HS-depleted mouse and human beta cells can be prevented by HS replacement using highly sulfated HS mimetics or analogues. T1D progression in NOD mice and recent-onset T1D in humans correlate with increased expression of heparanase by circulating leukocytes of myeloid origin and heparanase-expressing insulitis leukocytes. Treatment of NOD mice with the heparanase inhibitor and HS replacer, PI-88, significantly reduced T1D incidence by 50%, impaired the development of insulitis and preserved beta cell HS. These outcomes identified heparanase as a novel destructive tool in T1D, distinct from the conventional cytotoxic and apoptosis-inducing mechanisms of autoreactive T cells. In contrast to exogenous catalytically active heparanase, endogenous heparanase may function in HS homeostasis, gene expression and insulin secretion in normal beta cells and immune gene expression in leukocytes. In established diabetes, the interplay between hyperglycemia, local inflammatory cells (e.g. macrophages) and heparanase contributes to secondary micro- and macro-vascular disease. We have identified dual activity heparanase inhibitors/HS replacers as a novel class of therapeutic for preventing T1D progression and potentially for mitigating secondary vascular disease that develops with long-term T1D.
Asunto(s)
Diabetes Mellitus Tipo 1/enzimología , Glucuronidasa/metabolismo , Animales , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/patología , Glucuronidasa/antagonistas & inhibidores , Humanos , Islotes Pancreáticos/efectos de los fármacos , Islotes Pancreáticos/enzimología , Islotes Pancreáticos/patologíaRESUMEN
Prader-Willi syndrome (PWS) is a rare genetic condition with multi-system involvement. The literature was reviewed to describe neurodevelopment and the behavioural phenotype, endocrine and metabolic disorders and respiratory and sleep functioning. Implications for child and family quality of life were explored. Challenging behaviours contribute to poorer well-being and quality of life for both the child and caregiver. Recent evidence indicates healthy outcomes of weight and height can be achieved with growth hormone therapy and dietary restriction and should be the current target for all individuals with PWS. Gaps in the literature included therapies to manage challenging behaviours, as well as understanding the effects of growth hormone on respiratory and sleep function. New knowledge regarding the transition of children and families from schooling and paediatric health services to employment, accommodation and adult health services is also needed. Developing a national population-based registry could address these knowledge gaps and inform advocacy for support services that improve the well-being of individuals with PWS and their families.
Asunto(s)
Familia/psicología , Satisfacción Personal , Síndrome de Prader-Willi/fisiopatología , Calidad de Vida , Adolescente , Niño , Preescolar , Humanos , HiperfagiaRESUMEN
Bisphosphonate therapy is the mainstay of pharmacological intervention in young people with skeletal fragility. The evidence of its use in a variety of conditions remains limited despite over three decades of clinical experience. On behalf of the Australasian Paediatric Endocrine Group, this evidence-based consensus guideline presents recommendations and discusses the graded evidence (using the GRADE system) for these recommendations. Primary bone fragility disorders such as osteogenesis imperfecta are considered separately from osteoporosis secondary to other clinical conditions (such as cerebral palsy, Duchenne muscular dystrophy). The use of bisphosphonates in non-fragility conditions, such as fibrous dysplasia, avascular necrosis, bone cysts and hypercalcaemia, is also discussed. While these guidelines provide an evidence-based approach where possible, further research is required in all clinical applications in order to strengthen the recommendations made.
Asunto(s)
Conservadores de la Densidad Ósea/uso terapéutico , Difosfonatos/uso terapéutico , Osteogénesis Imperfecta/tratamiento farmacológico , Osteoporosis/tratamiento farmacológico , Adolescente , Densidad Ósea/efectos de los fármacos , Conservadores de la Densidad Ósea/efectos adversos , Parálisis Cerebral/complicaciones , Niño , Difosfonatos/efectos adversos , Humanos , Distrofia Muscular de Duchenne/complicaciones , Osteoporosis/etiologíaRESUMEN
Variants in the NR5A1 gene encoding SF1 have been described in a diverse spectrum of disorders of sex development (DSD). Recently, we reported the use of a targeted gene panel for DSD where we identified 15 individuals with a variant in NR5A1, nine of which are novel. Here, we examine the functional effect of these changes in relation to the patient phenotype. All novel variants tested had reduced trans-activational activity, while several had altered protein level, localization, or conformation. In addition, we found evidence of new roles for SF1 protein domains including a region within the ligand binding domain that appears to contribute to SF1 regulation of Müllerian development. There was little correlation between the severity of the phenotype and the nature of the NR5A1 variant. We report two familial cases of NR5A1 deficiency with evidence of variable expressivity; we also report on individuals with oligogenic inheritance. Finally, we found that the nature of the NR5A1 variant does not inform patient outcomes (including pubertal androgenization and malignancy risk). This study adds nine novel pathogenic NR5A1 variants to the pool of diagnostic variants. It highlights a greater need for understanding the complexity of SF1 function and the additional factors that contribute.
Asunto(s)
Trastornos del Desarrollo Sexual/diagnóstico , Trastornos del Desarrollo Sexual/genética , Estudios de Asociación Genética , Variación Genética , Fenotipo , Factor Esteroidogénico 1/genética , Alelos , Secuencia de Aminoácidos , Trastorno del Desarrollo Sexual 46,XY/diagnóstico , Trastorno del Desarrollo Sexual 46,XY/genética , Femenino , Estudios de Asociación Genética/métodos , Genotipo , Humanos , Masculino , Modelos Anatómicos , Mutación , Conformación Proteica , Dominios Proteicos/genética , Sitios de Empalme de ARN , Análisis de Secuencia de ADN , Factor Esteroidogénico 1/químicaRESUMEN
PURPOSE: To consider the role of anti-MOG Abs associated encephalitis in Hashimoto's Encephalitis (HE). RESULTS: A 10 year old girl with pre-existing Hashimoto's thyroiditis presented with dysarthria, ataxia and lethargy whilst euthyroid. Brain MRI showed multifocal T2 and FLAIR hyperintense lesions. She responded promptly to treatment with corticosteroids. Her clinical scenario was comparable to a sizeable minority of patients diagnosed with HE in the literature, who have similar brain MRIs. Serum was positive for anti-myelin oligodendrocyte glycoprotein (MOG) Ab, implicating this antibody-mediated process in this patient's illness. CONCLUSION: We hypothesize that anti-MOG Ab associated demyelination may underlie a subset of patients with HE.
Asunto(s)
Autoanticuerpos/inmunología , Encefalitis/inmunología , Enfermedad de Hashimoto/inmunología , Glicoproteína Mielina-Oligodendrócito/inmunología , Niño , Encefalitis/complicaciones , Femenino , Enfermedad de Hashimoto/complicaciones , Humanos , Imagen por Resonancia MagnéticaRESUMEN
BACKGROUND: Disorders of sex development (DSD) are congenital conditions in which chromosomal, gonadal, or phenotypic sex is atypical. Clinical management of DSD is often difficult and currently only 13% of patients receive an accurate clinical genetic diagnosis. To address this we have developed a massively parallel sequencing targeted DSD gene panel which allows us to sequence all 64 known diagnostic DSD genes and candidate genes simultaneously. RESULTS: We analyzed DNA from the largest reported international cohort of patients with DSD (278 patients with 46,XY DSD and 48 with 46,XX DSD). Our targeted gene panel compares favorably with other sequencing platforms. We found a total of 28 diagnostic genes that are implicated in DSD, highlighting the genetic spectrum of this disorder. Sequencing revealed 93 previously unreported DSD gene variants. Overall, we identified a likely genetic diagnosis in 43% of patients with 46,XY DSD. In patients with 46,XY disorders of androgen synthesis and action the genetic diagnosis rate reached 60%. Surprisingly, little difference in diagnostic rate was observed between singletons and trios. In many cases our findings are informative as to the likely cause of the DSD, which will facilitate clinical management. CONCLUSIONS: Our massively parallel sequencing targeted DSD gene panel represents an economical means of improving the genetic diagnostic capability for patients affected by DSD. Implementation of this panel in a large cohort of patients has expanded our understanding of the underlying genetic etiology of DSD. The inclusion of research candidate genes also provides an invaluable resource for future identification of novel genes.
Asunto(s)
Aberraciones Cromosómicas , Trastornos del Desarrollo Sexual/diagnóstico , Trastornos del Desarrollo Sexual/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Estudios de Cohortes , Trastornos del Desarrollo Sexual/patología , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Variación Genética , Gónadas/crecimiento & desarrollo , Gónadas/patología , Humanos , Masculino , Mutación/genética , Ovario/crecimiento & desarrollo , Ovario/patología , Linaje , Fenotipo , Testículo/crecimiento & desarrollo , Testículo/patologíaRESUMEN
AIM: A decline in asthma prevalence from 2000 to 2005 was reported previously. The objective is to examine the temporal trends for the prevalence of obesity and other childhood disorders and consider the extent to which associations between asthma and other co-morbidities can be accounted for by body mass index. METHODS: Serial cross-sectional surveys of primary school entrants (n = 18,999) in the Australian Capital Territory between 2001 and 2005 were used. Asthma, recent respiratory symptoms and diabetes data were extracted from parental reports. Anthropometric measurements were obtained from health assessments by school nurses. Child obesity was defined using the age and sex-specific Cole criteria. Time trends for the prevalence of obesity and other disorders, and the association between 'current asthma' and co-morbidities were analysed using multiple logistic regression and other analyses. RESULTS: Obesity prevalence was 5.24% in 2001 decreasing to 3.60% in 2005 (test of linear trend P = 0.02). Overweight (adjusted odds ratio (AOR) 1.30 (95% confidence interval (CI) 1.16, 1.46), P < 0.001) and obese (AOR 1.36 (95% CI 1.13, 1.62), P = 0.001) children were more likely to report 'asthma ever'. Children with diabetes (AOR 9.35 (95% CI 3.11, 28.12, P < 0.001)) and attention deficit (AOR 3.39 (95% CI 2.04, 5.64), P < 0.001) were more likely to report 'current asthma'. CONCLUSIONS: The pattern of association with co-morbidities was different for asthma and obesity. The temporal decline/plateau effect in 'current asthma' could not be explained by concurrent body mass index changes. The decline in obesity was largely driven by the 2005 findings. Longer term trends need to be evaluated further.
Asunto(s)
Asma/epidemiología , Diabetes Mellitus Tipo 1/epidemiología , Obesidad/epidemiología , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Territorio de la Capital Australiana/epidemiología , Índice de Masa Corporal , Preescolar , Comorbilidad/tendencias , Estudios Transversales , Eccema/epidemiología , Epilepsia/epidemiología , Femenino , Trastornos de la Audición/epidemiología , Humanos , Masculino , Prevalencia , Clase Social , Trastornos de la Visión/epidemiologíaRESUMEN
CONTEXT: We report hereditary pituitary hyperplasia. OBJECTIVE: The objective of the study was to describe the results of the clinical and laboratory analysis of this rare instance of hereditary pituitary hyperplasia. DESIGN: The study is a retrospective analysis of three cases from one family. SETTING: The study was conducted at the National Institutes of Health, a tertiary referral center. PATIENTS: A mother and both her sons had very early-onset gigantism associated with high levels of serum GH and prolactin. INTERVENTIONS: The condition was treated by total hypophysectomy. MAIN OUTCOME MEASURE(S): We performed clinical, pathological, and molecular evaluations, including evaluation basal and provocative endocrine testing, neuroradiological assessment, and assessment of the pituitary tissue by microscopic evaluation, immunohistochemistry, and electron microscopy. RESULTS: All three family members had very early onset of gigantism associated with abnormally high serum levels of GH and prolactin. Serum GHRH levels were not elevated in either of the boys. The clinical, radiographic, surgical, and histological findings indicated mammosomatotroph hyperplasia. The pituitary gland of both boys revealed diffuse mammosomatotroph hyperplasia of the entire pituitary gland without evidence of adenoma. Prolactin and GH were secreted by the same cells within the same secretory granules. Western blot and immunohistochemistry demonstrated expression of GHRH in clusters of cells distributed throughout the hyperplastic pituitary of both boys. CONCLUSIONS: This hereditary condition seems to be a result of embryonic pituitary maldevelopment with retention and expansion of the mammosomatotrophs. The findings suggest that it is caused by paracrine or autocrine pituitary GHRH secretion during pituitary development.
Asunto(s)
Gigantismo/congénito , Hipófisis/anomalías , Adenoma/patología , Adenoma/cirugía , Niño , Preescolar , Femenino , Gigantismo/cirugía , Hormona de Crecimiento Humana/sangre , Humanos , Hiperplasia/patología , Hipofisectomía , Lactante , Masculino , Hipófisis/patología , Hipófisis/cirugía , Neoplasias Hipofisarias/patología , Neoplasias Hipofisarias/cirugía , Prolactina/sangre , Resultado del TratamientoRESUMEN
OBJECTIVES: To estimate the incidence of cystic-fibrosis-related diabetes (CFRD) in youth from New South Wales (NSW) and the Australian Capital Territory (ACT), Australia and to examine demographic/clinical features at diagnosis. METHODS: Incident cases of CFRD in young people aged ≤ 18 years diagnosed during 2000 to 2008 were identified from four paediatric cystic fibrosis (CF) clinics and the NSW/ACT Australasian Paediatric Endocrine Group Diabetes Register. RESULTS: CFRD was diagnosed in 41 cases (59% girls). The estimated mean annual incidence of CFRD among patients with CF was 9.4 per 1000 person years (95% CI 6.8 to 12.8). Incidence increased from 2.0 per 1000 person years in 2000 to 22.1 per 1000 in 2008 (incidence RR 1.3, 95% CI 1.1 to 1.4). Haemoglobin A1c (HbA1c) was abnormal in the majority at diagnosis: median HbA1c was 6.9% (6.2-8.1%). More cases were diagnosed using an oral glucose tolerance test in 2007-2008 compared with previous years (61% vs 6%, p<0.001). CONCLUSIONS: CFRD is increasingly recognised and now affects approximately one in five young people with CF. The rising incidence is likely to be due to increased detection, resulting from greater awareness and changes in screening practices. Widespread uptake of consensus guidelines for screening will ensure accurate case detection, but will also impact on patient care and resource allocation.
Asunto(s)
Fibrosis Quística/complicaciones , Diabetes Mellitus/etiología , Adolescente , Territorio de la Capital Australiana/epidemiología , Niño , Preescolar , Fibrosis Quística/epidemiología , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/epidemiología , Esquema de Medicación , Femenino , Prueba de Tolerancia a la Glucosa , Hemoglobina Glucada/metabolismo , Humanos , Hipoglucemiantes/administración & dosificación , Incidencia , Lactante , Recién Nacido , Insulina/administración & dosificación , Masculino , Nueva Gales del Sur/epidemiología , Sistema de RegistrosRESUMEN
BACKGROUND: Reference intervals are essential in assessing the significance of laboratory results. There have been limited studies generating reference intervals from pediatric populations. We have studied a large cohort of healthy children on 3 separate occasions at 2yearly intervals. METHODS: 852 healthy 8year old children were enrolled in a community-based multidisciplinary longitudinal study investigating how early physical activity contributes to health. The same children came back for reassessment at ages 10 and 12years. Blood samples were analyzed for a total of 37 different chemistries, immunoassays or derived values. RESULTS: Reference intervals were derived for all the analytes for males and females separately. CONCLUSION: Whilst our results are largely in agreement with previously published work, we have shown that for a number of analytes, previously published work is distorted by subclinical disease.