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AIM: Hypernatraemia typically reflects dehydration, yet in rare instances may be caused by salt poisoning. Identifying these rare cases is a difficult challenge. Making the diagnosis of salt poisoning can have severe consequences, such as the removal of the child from its home or even prison sentences for the implicated carer. It is therefore imperative to get the diagnosis right. Guidelines for the assessment of hypernatraemia emphasise the importance of the fractional excretion of sodium to distinguish between dehydration and salt poisoning, but no generally accepted cut-off value exists. Opinions about the diagnosis of salt poisoning in some cases consequently may differ. Here, we aim to highlight the challenges and stimulate discussion on how to improve the tools for the assessment of hypernatraemia. METHODS: Report of a case of unexplained hypernatraemia in which the treating paediatrician raised the suspicion of salt poisoning. RESULTS: Two consulted experts made opposing judgements about the aetiology of the observed hypernatraemia. CONCLUSION: Clear diagnostic criteria for the diagnosis of salt poisoning are lacking and more data are needed for their establishment. Without this, victims may experience further harm and carers are at risk of devastating, yet potentially erroneous accusations.
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Hipernatremia , Sódio , Humanos , Desidratação/diagnóstico , Desidratação/etiologia , Hipernatremia/diagnóstico , Hipernatremia/etiologia , Hipernatremia/terapia , Fatores de Risco , Masculino , LactenteRESUMO
We report an unusually high number of cases (n = 26) of parechovirus infections in the cerebrospinal fluid (CSF) of neonates and infants admitted with sepsis in the United Kingdom during 8 May to 2 August 2016. Although such infections in neonates and infants are well-documented, parechovirus has not been routinely included in many in-house and commercial PCR assays for CSF testing. Clinicians should consider routine parechovirus testing in young children presenting with sepsis.
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Líquido Cefalorraquidiano/virologia , Parechovirus/isolamento & purificação , Infecções por Picornaviridae/diagnóstico , Sepse/epidemiologia , Sepse/virologia , Feminino , Genótipo , Hospitalização , Humanos , Lactente , Recém-Nascido , Tempo de Internação/estatística & dados numéricos , Masculino , Parechovirus/genética , Infecções por Picornaviridae/epidemiologia , Infecções por Picornaviridae/virologia , RNA Viral , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNA , Reino Unido/epidemiologiaRESUMO
Adrenal insufficiency (AI) is characterised by lack of cortisol production from the adrenal glands. This can be a primary adrenal disorder or secondary to adrenocorticotropic hormone deficiency or suppression from exogenous glucocorticoids. Symptoms of AI in children may initially be non-specific and include growth faltering, lethargy, poor feeding, weight loss, abdominal pain, vomiting and lingering illnesses. AI is treated with replacement doses of hydrocortisone. At times of physiological stress such as illness, trauma or surgery, there is an increased requirement for exogenous glucocorticoids, which if untreated can lead to an adrenal crisis and death. There are no unified guidelines for those <18 years old in the UK, leading to substantial variation in the management of AI. This paper sets out guidance for intercurrent illness, medical, dental and surgical procedures to allow timely and appropriate recognition and treatment of AI and adrenal crisis for children and young people.
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Insuficiência Adrenal , Diabetes Mellitus , Criança , Humanos , Adolescente , Consenso , Insuficiência Adrenal/tratamento farmacológico , Insuficiência Adrenal/diagnóstico , Hidrocortisona/uso terapêutico , Glucocorticoides/uso terapêutico , Diabetes Mellitus/tratamento farmacológicoRESUMO
BACKGROUND: Pseudohypoparathyroidism type Ib (PHP-Ib) is due to epigenetic changes at the imprinted GNAS locus, including loss of methylation at the A/B differentially methylated region (DMR) and sometimes at the XL and AS DMRs and gain of methylation at the NESP DMR. OBJECTIVE: To investigate if quantitative measurement of the methylation at the GNAS DMRs identifies subtypes of PHP-Ib. DESIGN AND METHODS: In 19 patients with PHP-Ib and 7 controls, methylation was characterised at the four GNAS DMRs through combined bisulfite restriction analysis and quantified through cytosine specific real-time PCR in blood lymphocyte DNA. RESULTS: A principal component analysis using the per cent of methylation at seven cytosines of the GNAS locus provided three clusters of subjects (controls n=7, autosomal dominant PHP-Ib with loss of methylation restricted to the A/B DMR n=3, and sporadic PHP-Ib with broad GNAS methylation changes n=16) that matched perfectly the combined bisulfite restriction analysis classification. Furthermore, three sub-clusters of patients with sporadic PHP-Ib, that displayed different patterns of methylation, were identified: incomplete changes at all DMRs compatible with somatic mosaicism (n=5), profound epigenetic changes at all DMRs (n=8), and unmodified methylation at XL in contrast with the other DMRs (n=3). Interestingly, parathyroid hormone concentration at the time of diagnosis correlated with the per cent of methylation at the A/B DMR. CONCLUSION: Quantitative assessment of the methylation in blood lymphocyte DNA is of clinical relevance, allows the diagnosis of PHP-Ib, and identifies subtypes of PHP-Ib. These epigenetic findings suggest mosaicism at least in some patients.
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Metilação de DNA/genética , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Adolescente , Adulto , Criança , Cromograninas , Epigênese Genética , Feminino , Genes Dominantes , Humanos , Masculino , Fenótipo , Pseudo-Hipoparatireoidismo/classificação , Pseudo-Hipoparatireoidismo/genética , Análise de Sequência de DNA , Pseudo-HipoparatireoidismoRESUMO
CONTEXT: 17α-Hydroxylase/17,20-lyase deficiency (17OHD) caused by mutations in the CYP17A1 gene is a rare form of congenital adrenal hyperplasia typically characterised by cortisol deficiency, mineralocorticoid excess and sex steroid deficiency. OBJECTIVE: To examine the phenotypic spectrum of 17OHD by clinical and biochemical assessment and corresponding in silico and in vitro functional analysis. DESIGN: Case series. PATIENTS AND RESULTS: We assessed eight patients with 17OHD, including four with extreme 17OHD phenotypes: two siblings presented with failure to thrive in early infancy and two with isolated sex steroid deficiency and normal cortisol reserve. Diagnosis was established by mass spectrometry-based urinary steroid profiling and confirmed by genetic CYP17A1 analysis, revealing homozygous and compound heterozygous sequence variants. We found novel (p.Gly111Val, p.Ala398Glu, p.Ile371Thr) and previously described sequence variants (p.Pro409Leu, p.Arg347His, p.Gly436Arg, p.Phe53/54del, p.Tyr60IlefsLys88X). In vitro functional studies employing an overexpression system in HEK293 cells showed that 17,20-lyase activity was invariably decreased while mutant 17α-hydroxylase activity retained up to 14% of WT activity in the two patients with intact cortisol reserve. A ratio of urinary corticosterone over cortisol metabolites reflective of 17α-hydroxylase activity correlated well with clinical phenotype severity. CONCLUSION: Our findings illustrate the broad phenotypic spectrum of 17OHD. Isolated sex steroid deficiency with normal stimulated cortisol has not been reported before. Attenuation of 17α-hydroxylase activity is readily detected by urinary steroid profiling and predicts phenotype severity. SIGNIFICANCE STATEMENT: Here we report, supported by careful phenotyping, genotyping and functional analysis, a prismatic case series of patients with congenital adrenal hyperplasia due to 17α-hydroxylase (CYP17A1) deficiency (17OHD). These range in severity from the abolition of function, presenting in early infancy, and unusually mild with isolated sex steroid deficiency but normal ACTH-stimulated cortisol in adult patients. These findings will guide improved diagnostic detection of CYP17A1 deficiency.
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Esteroide 17-alfa-Hidroxilase/genética , Adolescente , Hiperplasia Suprarrenal Congênita/genética , Amenorreia/genética , Simulação por Computador , Corticosterona/urina , Insuficiência de Crescimento/enzimologia , Insuficiência de Crescimento/genética , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Hormônios Esteroides Gonadais/deficiência , Ginecomastia/etiologia , Ginecomastia/genética , Células HEK293 , Humanos , Hidrocortisona/deficiência , Lactente , Recém-Nascido , Masculino , Mineralocorticoides/metabolismo , Mutação/genética , Fenótipo , Esteroides/urina , Adulto JovemRESUMO
CONTEXT: Assessing dental anxiety as a predictor of the likely behavior of the child in the dental operatory is of paramount importance for a clinician to render quality care. AIM: This study aims to correlate the dental anxiety of preschool children as shown during the doll placement test with that of their behavioral patterns during the first dental visit. SETTINGS AND DESIGN: This cross-sectional study was conducted between the ages of 3-7 years. MATERIALS AND METHODS: During their first dental visit, the background variables were elicited from parent/guardian at the reception desk. Later at the play area, the child was given a set of dolls representing dentist, child, and mother to place them in a model dental office having a dental chair. The child was then taken for the initial oral examination, during which the behavior of the child was rated using Frankl's Behavior Rating Scale. The data collected were analyzed using Chi-square test and binary regression analysis. RESULTS: The observed association between the doll placement pattern and the behavior of the patient during dental treatment was statistically significant (P < 0.001). The binary regression analysis showed that the child's unpleasant previous medical and parent's unpleasant dental experiences had higher odds favoring uncooperative behavior (46.63 and 41.93, respectively). CONCLUSIONS: The child's behavior on the dental chair is associated with the doll placement pattern, which is also influenced by experiences of the child during his/her encounter with the medical doctor and previous dental experiences of their parents.
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Ansiedade ao Tratamento Odontológico , Assistência Odontológica para Crianças , Criança , Comportamento Infantil , Pré-Escolar , Estudos Transversais , Assistência Odontológica , Feminino , Humanos , Masculino , PaisRESUMO
Background The objective of the study was to evaluate the long-term outcome of paediatric-onset hyperthyroidism with follow-up into adulthood and to identify any early predictors of a need for definitive therapy (DT). Methods In a retrospective analysis of patients diagnosed with hyperthyroidism under the age of 18 years and at follow-up, a comparison was made by categorising them into those who underwent definitive therapy (DT group), i.e. thyroidectomy/radioactive iodine (RAI), those who remained on antithyroid drugs (ATD) (CBZ group) and those who had complete remission (RE group). Results Sixty-one (49 females, 12 males) patients with a median age of 15.1 years (range: 3.6-18) at diagnosis were studied. The duration of the first course of ATD varied from <1 year (7%), 1-2 years (26%), >2 years (46%) and ATD never discontinued (21%). Disease relapsed in 69% of patients with <1 year of ATD vs. 79% with >2 years of ATD. At follow-up, the median duration since diagnosis was 8.75 years (range 2.0-20.7 years) and the median age at follow-up was 23.2 years (8-36 years). Thirty-three percent (20/61) had undergone DT (DT group) - with 16.5% (n=10) on RAI and 16.5% (n=10) on surgery, 36% (22/61) were on ATD (CBZ group), whilst 32% (19/61) had undergone full remission (RE group). The comparison did not identify any statistically significant difference for predictor factors at diagnosis including age, T4 and free T4 levels, thyroid peroxidise antibody levels (TPO) and the duration of the first course of carbimazole (CBZ) treatment. Conclusion Long-term complete remission of paediatric-onset hyperthyroidism in our study was 31%. There were no predictors identified that could help predict the long-term outcome, especially into adulthood.
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Antitireóideos/uso terapêutico , Hipertireoidismo/terapia , Radioisótopos do Iodo/uso terapêutico , Tireoidectomia/métodos , Adolescente , Criança , Feminino , Seguimentos , Humanos , Hipertireoidismo/patologia , Masculino , Indução de Remissão , Estudos Retrospectivos , Testes de Função Tireóidea , Resultado do TratamentoRESUMO
Comparison of children hospitalized with enterovirus or human parechovirus (HPeV) detected in their cerebrospinal fluid revealed that HPeV infections presented with more persistent fever, irritability and feeding problems, more frequent leukopenia and lymphopenia and higher admission rates to high dependency or intensive care units. Few HPeV cases were followed up, further studies on long-term outcomes are needed.
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Líquido Cefalorraquidiano/virologia , Infecções por Enterovirus/patologia , Enterovirus/isolamento & purificação , Parechovirus/isolamento & purificação , Infecções por Picornaviridae/patologia , Feminino , Hospitalização , Humanos , Lactente , Recém-Nascido , MasculinoRESUMO
A previously well, 4-year-old girl presented with a 4-6 weeks' history of increased appetite, weight loss, tiredness, sleep difficulty, excessive sweating, swelling in the neck and new-onset 'prominent, protruding eyes.' Family history revealed paternal grandmother receiving treatment for hyperthyroidism. Clinical assessment demonstrated features of thyrotoxicosis (tachycardia, warm peripheries, small smooth goitre with no nodules, exophthalmos). TFT (Free T4=101 pmol/L, thyroid-stimulating hormone <0.05 mIU/L) with raised thyroid peroxidase antibody levels (TPO=541 IU/mL) confirmed autoimmune hyperthyroidism. Observation on the ward showed features of thyrotoxic crisis with persistent severe tachycardia on ECG (sinus tachycardia with left ventricular hypertrophy (LVH)) and hypertension. Ultrasound thyroid showed diffuse thyroiditis with no focal lesion. Echocardiogram confirmed the above findings. A diagnosis of Graves' disease with thyrotoxic crisis was made. Antithyroid treatment (carbimazole) and beta-blocker (propranolol) was commenced. Thyrotoxic crisis resolved over 2 weeks and the child has continued to respond to carbimazole treatment at 1-year follow-up.
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Doença de Graves/diagnóstico , Crise Tireóidea/etiologia , Carbimazol/uso terapêutico , Pré-Escolar , Feminino , Doença de Graves/tratamento farmacológico , Humanos , Propranolol/uso terapêutico , Crise Tireóidea/tratamento farmacológico , Crise Tireóidea/metabolismo , Resultado do TratamentoRESUMO
CONTEXT: Lower TSH screening cutoffs have doubled the ascertainment of congenital hypothyroidism (CH), particularly cases with a eutopically located gland-in-situ (GIS). Although mutations in known dyshormonogenesis genes or TSHR underlie some cases of CH with GIS, systematic screening of these eight genes has not previously been undertaken. OBJECTIVE: Our objective was to evaluate the contribution and molecular spectrum of mutations in eight known causative genes (TG, TPO, DUOX2, DUOXA2, SLC5A5, SLC26A4, IYD, and TSHR) in CH cases with GIS. Patients, Design, and Setting: We screened 49 CH cases with GIS from 34 ethnically diverse families, using next-generation sequencing. Pathogenicity of novel mutations was assessed in silico. PATIENTS, DESIGN, AND SETTING: We screened 49 CH cases with GIS from 34 ethnically diverse families, using next-generation sequencing. Pathogenicity of novel mutations was assessed in silico. RESULTS: Twenty-nine cases harbored likely disease-causing mutations. Monogenic defects (19 cases) most commonly involved TG (12), TPO (four), DUOX2 (two), and TSHR (one). Ten cases harbored triallelic (digenic) mutations: TG and TPO (one); SLC26A4 and TPO (three), and DUOX2 and TG (six cases). Novel variants overall included 15 TG, six TPO, and three DUOX2 mutations. Genetic basis was not ascertained in 20 patients, including 14 familial cases. CONCLUSIONS: The etiology of CH with GIS remains elusive, with only 59% attributable to mutations in TSHR or known dyshormonogenesis-associated genes in a cohort enriched for familial cases. Biallelic TG or TPO mutations most commonly underlie severe CH. Triallelic defects are frequent, mandating future segregation studies in larger kindreds to assess their contribution to variable phenotype. A high proportion (â¼41%) of unsolved or ambiguous cases suggests novel genetic etiologies that remain to be elucidated.
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Autoantígenos/genética , Hipotireoidismo Congênito/genética , Iodeto Peroxidase/genética , Proteínas de Ligação ao Ferro/genética , Receptores da Tireotropina/genética , Tireoglobulina/genética , Humanos , Mutação , Linhagem , FenótipoRESUMO
Working practice in neonatal units, like other medical and surgical specialties, is undergoing drastic changes to incorporate current legal and ethical requirements. We surveyed the current working practices of 60 neonatal units in this country. Consent appeared to be implied for routine procedures. Variable rates of consent were reported for specialised interventions and the surgical team was consistently involved in obtaining consent for all surgical procedures. There is great variation in practices for seeking consent in neonatal units in this country.
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Unidades de Terapia Intensiva Neonatal/organização & administração , Política Organizacional , Consentimento dos Pais/estatística & dados numéricos , Autopsia , Coleta de Dados , Guias como Assunto , Humanos , Lactente , Recém-Nascido , Procedimentos Cirúrgicos Operatórios , Reino UnidoRESUMO
Infacol (Forest Laboratories UK, Kent, UK) is a widely available over-the-counter preparation used to relieve colic symptoms in neonates and infants. The active ingredient is simeticone. No drug interactions with simeticone are documented in the current summary of product characteristics. The authors report the case of an infant with confirmed congenital hypothyroidism on levothyroxine who experienced a possible drug interaction with simeticone. Despite adequate levothyroxine dosage, thyroid stimulating hormone (TSH) was high, suggesting undertreatment. Questioning revealed the child was taking Infacol drops before feeds while on levothyroxine. The colic drops were immediately discontinued and TSH promptly normalised with a reduction in thyroxine requirement to an age appropriate dosage. Drug interaction of thyroxine with simeticone has not been reported previously and is not listed in the British National Formulary for Children. Clinicians and parents need to be aware of this interaction to avoid unnecessary undertreatment and prevent potential long-term neurological sequelae.
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Antiespumantes/farmacologia , Cólica/tratamento farmacológico , Hipotireoidismo Congênito/tratamento farmacológico , Simeticone/farmacologia , Tiroxina/antagonistas & inibidores , Hipotireoidismo Congênito/sangue , Interações Medicamentosas , Resistência a Medicamentos , Feminino , Humanos , Recém-Nascido , Medicamentos sem Prescrição , Tireotropina/sangue , Tiroxina/sangueRESUMO
Growth impairment and adrenal suppression secondary to inhaled corticosteroids (ICS) is a well-recognised phenomenon. We report a 13-year-old boy, treated long-term for asthma, who presented with short stature while on low-dose inhaled corticosteroid (beclomethasone 200 microg/d). Investigations revealed evidence of severe adrenal suppression. Weaning off the steroid treatment resulted in recovery of adrenal activity and rapid growth. While low-dose ICS are normally considered to have few side effects, this case illustrates the extreme variability of individual sensitivity and the need for careful surveillance of all children treated with long-term steroids.