RESUMO
Kabuki Syndrome (KS) is a multisystemic genetic disorder. A portion of patients has immunological manifestations characterized by increased susceptibility to infections and autoimmunity. Aiming to describe the clinical and laboratory immunological aspects of KS, we conducted a retrospective multicenter observational study on patients with KS treated in centers affiliated to the Italian Primary Immunodeficiency Network.Thirty-nine patients were enrolled, with a median age at evaluation of 10 years (range: 3 m-21y). All individuals had organ malformations of variable severity. Congenital heart defect (CHD) was present in 19/39 patients (49%) and required surgical correction in 9/39 (23%), with associated thymectomy in 7/39 (18%). Autoimmune cytopenia occurred in 6/39 patients (15%) and was significantly correlated with thymectomy (p < 0.002), but not CHD. Individuals with cytopenia treated with mycophenolate as long-term immunomodulatory treatment (n = 4) showed complete response. Increased susceptibility to infections was observed in 22/32 patients (69%). IgG, IgA, and IgM were low in 13/29 (45%), 13/30 (43%) and 4/29 (14%) patients, respectively. Immunoglobulin substitution was required in three patients. Lymphocyte subsets were normal in all patients except for reduced naïve T-cells in 3/15 patients (20%) and reduced memory switched B-cells in 3/17 patients (18%). Elevated CD3 + TCRαß + CD4-CD8-T-cells were present in 5/17 individuals (23%) and were correlated with hematological and overall autoimmunity (p < 0.05).In conclusion, immunological manifestations of KS in our cohort include susceptibility to infections, antibody deficiency, and autoimmunity. Autoimmune cytopenia is correlated with thymectomy and elevated CD3 + TCRαß + CD4-CD8-T-cells, and benefits from treatment with mycophenolate.
Assuntos
Anormalidades Múltiplas , Face/anormalidades , Doenças Hematológicas , Doenças Vestibulares , Humanos , Feminino , Estudos Retrospectivos , Masculino , Criança , Doenças Hematológicas/imunologia , Doenças Hematológicas/terapia , Adolescente , Itália , Doenças Vestibulares/imunologia , Pré-Escolar , Adulto Jovem , Anormalidades Múltiplas/imunologia , Lactente , Autoimunidade , AdultoRESUMO
Congenital growth hormone deficiency (GHD) is a rare disease caused by disorders affecting the morphogenesis and function of the pituitary gland. It is sometimes found in isolation but is more frequently associated with multiple pituitary hormone deficiency. In some cases, GHD may have a genetic basis. The many clinical signs and symptoms include hypoglycaemia, neonatal cholestasis and micropenis. Diagnosis should be made by laboratory analyses of the growth hormone and other pituitary hormones, rather than by cranial imaging with magnetic resonance imaging. When diagnosis is confirmed, hormone replacement should be initiated. Early GH replacement therapy leads to more positive outcomes, including reduced hypoglycaemia, growth recovery, metabolic asset, and neurodevelopmental improvements.
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Hormônio do Crescimento Humano , Hipoglicemia , Hipopituitarismo , Recém-Nascido , Humanos , Hipopituitarismo/diagnóstico , Hipopituitarismo/tratamento farmacológico , Hipopituitarismo/etiologia , Hormônio do Crescimento Humano/uso terapêutico , Hormônios Hipofisários , Hormônio do Crescimento/uso terapêutico , Hipoglicemia/tratamento farmacológicoRESUMO
Metabolic bone disease of prematurity (MBD) is a condition of reduced bone mineral content (BMC) compared to that expected for gestational age (GA). Preterm birth interrupts the physiological process of calcium (Ca) and phosphorus (P) deposition that occurs mostly in the third trimester of pregnancy, leading to an inadequate bone mineralization during intrauterine life (IUL). After birth, an insufficient intake of Ca and P carries on this alteration, resulting in overt disease. If MBD is often a self-limited condition, in some cases it could hesitate the permanent alteration of bone structures with growth faltering and failure to wean off mechanical ventilation due to excessive chest wall compliance. Despite advances in neonatal intensive care, MBD is still frequent in preterm infants, with an incidence of 16−23% in very-low-birth-weight (VLBW, birth weight <1500 g) and 40−60% in extremely low-birth-weight (ELBW, birth weight <1000 g) infants. Several risk factors are associated with MBD (e.g., malabsorption syndrome, parenteral nutrition (PN), pulmonary bronchodysplasia (BPD), necrotizing enterocolitis (NEC), and some chronic medications). The aim of this study was to evaluate the rate of MBD in a cohort of VLBWI and the role of some risk factors. We enrolled 238 VLBWIs (107 male). 52 subjects were classified as increased risk (G1) and 186 as standard risk (G2) according to serum alkaline phosphatase (ALP) and phosphorus (P) levels. G1 subjects have lower GA (p < 0.01) and BW (p < 0.001). Moreover, they need longer PN support (p < 0.05) and invasive ventilation (p < 0.01). G1 presented a higher rate of BPD (p = 0.026). At linear regression analysis, BW and PN resulted as independent predictor of increased risk (p = 0.001, p = 0.040, respectively). Preventive strategies are fundamental to prevent chronic alteration in bone structures and to reduce the risk of short stature. Screening for MBD based on serum ALP could be helpful in clinical practice to identify subjects at increased risk.
Assuntos
Doenças Ósseas Metabólicas , Enterocolite Necrosante , Nascimento Prematuro , Fosfatase Alcalina , Peso ao Nascer , Doenças Ósseas Metabólicas/epidemiologia , Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/prevenção & controle , Cálcio , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso , Masculino , Fósforo , Gravidez , Fatores de RiscoRESUMO
Oxidative stress is the result of an imbalance in the redox state in a cell or a tissue. When the production of free radicals, which are physiologically essential for signaling, exceeds the antioxidant capability, pathological outcomes including oxidative damage to macromolecules, aberrant signaling, and inflammation can occur. Down syndrome (DS) and Williams-Beuren syndrome (WBS) are well-known and common genetic conditions with multi-systemic involvement. Their etiology is linked to oxidative stress with important causative genes, such as SOD-1 and NCF-1, respectively, of the diseases being primarily involved in the regulation of the redox state. Early aging, dementia, autoimmunity, and chronic inflammation are some of the main characteristics of these conditions that can be associated with oxidative stress. In recent decades, there has been a growing interest in the possible role of oxidative stress and inflammation in the pathology of these conditions. However, at present, few studies have investigated these correlations. We provide an overview of the current literature concerning the role of oxidative stress and oxidative damage in genetic syndromes with a focus on Down syndrome and WBS. We hope to provide new insights to improve the management of complications related to these diseases.
Assuntos
Síndrome de Down/metabolismo , Estresse Oxidativo , Síndrome de Williams/metabolismo , HumanosAssuntos
Mutação com Ganho de Função , Transplante de Células-Tronco Hematopoéticas , Fator de Transcrição STAT3 , Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Fator de Transcrição STAT3/genética , Masculino , Transtornos do Crescimento/etiologia , Transtornos do Crescimento/genética , Feminino , CriançaRESUMO
OBJECTIVE: Although emerging data indicate that obese/overweight children are more likely to develop functional gastrointestinal disorders (FGIDs) than normal-weight peers, contrasting results have been reported. The present observational, case-control study aimed at estimating the prevalence of FGIDs in obese/overweight children compared to normal-weight peers. METHODS: Consecutive obese and overweight children aged 4 to 18 years attending the obesity outpatient clinic were enrolled as study cases. Normal-weight children were enrolled as comparison group. All the enrolled patients received a thorough health examination from both a pediatric endocrinologist and gastroenterologist. Moreover, they were asked to fill out the Rome III questionnaire for the diagnosis of FGIDs. Data were analyzed to compare the prevalence of FGIDs between cases and controls. RESULTS: Throughout the study period we enrolled 103 cases and 115 controls. No significant age and sex differences were found between the 2 groups. FGIDs were significantly more prevalent in obese/overweight compared to normal-weight children (47.57% vs 17.39%; Pâ<â0.0001). Increased prevalence was observed for functional constipation (18.44% vs 7.82%; Pâ=â0.025), functional dyspepsia (23.33% vs 6.95%; Pâ=â0.001), and irritable bowel syndrome (10.67% vs 2.60%; Pâ=â0.024), whereas no difference was observed for functional abdominal pain (1.94% vs 2.60%; Pâ=â1.00). CONCLUSIONS: Our data suggest that there is a link between excess body fat and FGIDs in children. This finding may offer a model of patients in which the effects of food and nutritional substances, the gut microbial environment, and psychosocial factors are fitting well with the emerging biopsychosocial conceptual model for FGIDs.
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Gastroenteropatias/epidemiologia , Sobrepeso , Obesidade Infantil , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Gastroenteropatias/etiologia , Humanos , Itália/epidemiologia , Masculino , Prevalência , Inquéritos e QuestionáriosRESUMO
OBJECTIVES: Juvenile idiopathic arthritis (JIA) may affect natural growth. The aim of the study has been to assess auxological parameters of JIA patients, receiving different anti-rheumatic treatments. METHODS: This is a retrospective study; JIA patients were recruited from the Rheumatology Unit of Anna Meyer Children's University Hospital of Florence, Italy from March 1996 to June 2016. RESULTS: Two hundred and thirty-two patients were included in the current study. The best result in terms of catch-up growth occurred in systemic JIA patients. All JIA categories showed standard deviation score (SDS) gain for height except those belonging to enthesitis related arthritis category. Patients treated with disease-modifying anti-rheumatic drugs (DMARDs) only maintained constant growth during study follow-up. Patients who needed biologic therapy showed an impaired growth during pre-DMARDs treatment and an increased growth velocity mostly during biologic therapy. Body mass index (BMI) decreased in almost all JIA categories. The best BMI reduction was observed among patient receiving biologic drugs. CONCLUSIONS: Patients with JIA followed in our centre had a gain of height SDS and lost BMI SDS in 5 years of follow-up. We observed a stable and good pattern of growth in patients treated with DMARDs and an increased growth velocity during biologic treatment.
Assuntos
Antirreumáticos/uso terapêutico , Artrite Juvenil/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Estatura , Índice de Massa Corporal , Desenvolvimento Infantil , Fatores Etários , Antirreumáticos/efeitos adversos , Artrite Juvenil/diagnóstico , Artrite Juvenil/fisiopatologia , Produtos Biológicos/efeitos adversos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Itália , Masculino , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: The cardiovascular disease risk was assessed in metabolically healthy obese (MHO) children, obese children with metabolic disorders (MUO), and to a control group of normal-weight children using carotid intima-media thickness (CIMT). METHODS: Participants were 204 obese children (114 M, 90 F), including 162 MUO (74 M, 88 F) and 42 MHO (24 M, 18 F), and 99 gender- and age-matched controls (45 M, 54 F). Glucose, triglycerides, total cholesterol, high-density and low-density lipoprotein cholesterol, and other serum values were determined in peripheral blood. Anthropometric parameters, blood pressure, and a carotid Doppler ultrasound scan were also acquired. The mean CIMT of obese subjects and controls was compared by analysis of variance. Abnormality of even one of the metabolic parameters assessed involved assignation to the MUO group. Mean CIMT was compared in MHO and MUO children. RESULTS: Mean CIMT in control children was 402.97 ± 53.18 µm (left carotid artery) and 377.85 ± 52.47 µm (right carotid artery). In MHO and MUO patients CIMT was respectively 453.29 ± 62.04 and 460.17 ± 92.22 µm (left carotid artery) and 446.36 ± 49.21 and 456.30 ± 85.7 µm (right carotid artery). The mean CIMT was not significantly different in MUO and MHO children, whereas it showed a significant difference between both groups of obese children and controls (p < 0.01). CONCLUSION: CIMT was significantly greater in obese patients, also in those without metabolic alterations, than in normal-weight children. Obesity is therefore an important risk factor for cardiovascular disease in itself, also in the absence of metabolic abnormalities.
Assuntos
Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/etiologia , Espessura Intima-Media Carotídea , Síndrome Metabólica/complicações , Obesidade Metabolicamente Benigna/complicações , Obesidade Infantil/complicações , Ultrassonografia Doppler , Adolescente , Fatores Etários , Biomarcadores/sangue , Glicemia/análise , Doenças das Artérias Carótidas/diagnóstico por imagem , Criança , Feminino , Humanos , Insulina/sangue , Lipídeos/sangue , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/diagnóstico , Obesidade Metabolicamente Benigna/sangue , Obesidade Metabolicamente Benigna/diagnóstico , Obesidade Infantil/sangue , Obesidade Infantil/diagnóstico , Valor Preditivo dos Testes , Fatores de RiscoRESUMO
Primary distal renal tubular acidosis is a rare genetic disease. Mutations in SLC4A1, ATP6V0A4, and ATP6V1B1 genes have been described as the cause of the disease, transmitted as either an autosomal dominant or recessive trait. Particular clinical features, such as sensorineural hearing loss, have been mainly described in association with mutations in one gene instead of the others. Nevertheless, the diagnosis of distal renal tubular acidosis is essentially based on clinical and laboratory findings, and the series of patients described so far are usually represented by small cohorts. Therefore, a strict genotype-phenotype correlation is still lacking, and questions about whether clinical and laboratory data should direct the genetic analysis remain open. Here, we applied next-generation sequencing in 89 patients with a clinical diagnosis of distal renal tubular acidosis, analyzing the prevalence of genetic defects in SLC4A1, ATP6V0A4, and ATP6V1B1 genes and the clinical phenotype. A genetic cause was determined in 71.9% of cases. In our group of sporadic cases, clinical features, including sensorineural hearing loss, are not specific indicators of the causal underlying gene. Mutations in the ATP6V0A4 gene are quite as frequent as mutations in ATP6V1B1 in patients with recessive disease. Chronic kidney disease was frequent in patients with a long history of the disease. Thus, our results suggest that when distal renal tubular acidosis is suspected, complete genetic testing could be considered, irrespective of the clinical phenotype of the patient.
Assuntos
Acidose Tubular Renal/genética , Proteína 1 de Troca de Ânion do Eritrócito/genética , Doenças Raras/genética , Insuficiência Renal Crônica/genética , ATPases Vacuolares Próton-Translocadoras/genética , Adolescente , Adulto , Criança , Pré-Escolar , Análise Mutacional de DNA , Feminino , Estudos de Associação Genética , Testes Genéticos , Genótipo , Perda Auditiva Neurossensorial/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Mutação , Fenótipo , Estudos Retrospectivos , Adulto JovemRESUMO
AIM: The effect of a supernumerary X chromosome on bones has not been reported, and this study evaluated bone mineral status and metabolism in nonmosaic triple X syndrome. METHODS: This cross-sectional study comprised 19 girls, with a median age of 10.9 years, with nonmosaic triple X syndrome and a control group matched for age and body size. We studied ionised and total calcium, phosphate, parathyroid hormone (PTH), 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D, osteocalcin, bone alkaline phosphatase levels and urinary deoxypyridinoline concentrations. We also measured the phalangeal amplitude-dependent speed of sound (AD-SoS) and the bone transmission time (BTT) Z-scores. RESULTS: Patients with nonmosaic triple X syndrome showed significantly reduced AD-SoS (p < 0.005) and BTT Z-scores (p < 0.0001) compared to the control group, and these results persisted when we divided the sample into prepubertal and pubertal patients (p < 0.05). These patients also had significantly reduced ionised calcium (p < 0.005) and 25(OH)D levels (p < 0.005) and higher phosphate (p < 0.0001) and PTH (p < 0.0001) levels. CONCLUSION: Subjects with nonmosaic triple X syndrome exhibited a significant impairment in bone mineral status and metabolism similar to other X polisomy, such as Klinefelter's syndrome. This suggests the presence of a primary bone deficit and the need for regular and close monitoring of these subjects.
Assuntos
Osso e Ossos/metabolismo , Calcificação Fisiológica , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/metabolismo , Adolescente , Criança , Cromossomos Humanos X/metabolismo , Estudos Transversais , Humanos , Aberrações dos Cromossomos Sexuais , TrissomiaRESUMO
BACKGROUND: Secondary endoscopic third ventriculostomy (ETV) for the management of shunt failure may be efficacious, though it may be followed by more frequent complications (including endocrinological impairment, e.g., amenorrhea) compared to primary ETV. These complications are usually underreported in the literature. AIM: We report a case of secondary amenorrhea after ETV for the management of shunt failure in a young woman with hydrocephalus associated with myelomeningocele. METHODS: A 25-year-old woman affected by hydrocephalus and myelomeningocele was admitted for secondary ETV for the management of shunt failure. The endoscopic procedure was preferred over shunt revision based on good results of secondary ETV, especially in patients with hydrocephalus associated with Chiari II malformation and spina bifida. RESULTS: Despite the surgery being uneventful, the patient had early (postoperative seizure) and late (secondary amenorrhea) complications. In the early postoperative period, she received external ventricular drainage followed by VP shunt reimplantation 2 weeks later. There was no neurological morbidity, but 1 month after the ETV she reported secondary amenorrhea and weight gain. Laboratory investigations ruled out hyperprolactinemia, which had been treated with cabergoline administration with no efficacy since the patient was still without regular periods 1 year later. CONCLUSION: ETV may be followed by endocrinological complications like amenorrhea that are rarely reported.
Assuntos
Amenorreia/etiologia , Hidrocefalia/cirurgia , Disrafismo Espinal/cirurgia , Terceiro Ventrículo/cirurgia , Derivação Ventriculoperitoneal/efeitos adversos , Ventriculostomia/métodos , Adulto , Malformação de Arnold-Chiari/complicações , Feminino , Humanos , Neuroendoscopia/métodos , Complicações Pós-Operatórias , Reoperação/efeitos adversosRESUMO
BACKGROUND: Deletions on the distal portion of the long arm of chromosome 6 are relatively uncommon, and only a small number occurs in the paternal copy, causing growth abnormalities. As a result, extensive clinical descriptions are lacking. CASE PRESENTATION: We describe a male of Italian descent born at 35 weeks by elective caesarean delivery presenting hypoplastic left colon, bilateral inguinal hernia, dysplastic tricuspid and pulmonary valves, premature ventricular contractions, recurrent otitis media, poor feeding, gastro-oesophageal reflux, bilateral pseudopapilledema, and astigmatism. He also showed particular facial dysmorphisms and postnatal growth failure. Early psychomotor development was mildly delayed. At 3.75 years, he was evaluated for severe short stature (-2.98 SD) and delayed bone age. He showed an insulin-like growth factor 1 concentration (IGF-1) in the low-normal range. Growth hormone stimulation tests showed a low response to clonidine and insulin. Magnetic resonance imaging showed hypophyseal hypoplasia. Genetic evaluation by Single Nucleotide Polymorphism arrays showed a de novo 6q24.2-q25.2 deletion on paternal chromosome 6. CONCLUSION: We confirm that this is a new congenital malformation syndrome associated with a deletion of 6q24.2-q25.2 on paternal chromosome 6. We suggest evaluating the growth hormone axis in children with 6q24.2-q25.2 deletions and growth failure.
Assuntos
Anormalidades Múltiplas/genética , Deleção Cromossômica , Cromossomos Humanos Par 6/genética , Transtornos do Crescimento/genética , Hormônio do Crescimento/deficiência , Anormalidades Múltiplas/tratamento farmacológico , Anormalidades Múltiplas/patologia , Hibridização Genômica Comparativa , Ecocardiografia , Seguimentos , Transtornos do Crescimento/tratamento farmacológico , Transtornos do Crescimento/patologia , Hormônio do Crescimento/administração & dosagem , Humanos , Itália , Cariotipagem , Imageamento por Ressonância Magnética , MasculinoRESUMO
BACKGROUND: Agenesis of the internal carotid artery (ICA) is a rare congenital abnormality, sporadically reported to be associated with a combined congenital hypopituitarism. Nevertheless, only a few cases have been extensively described, and none of these have been characterized by an isolated growth hormone (GH) deficiency. CASE PRESENTATION: Here, we describe a 17-year old boy referred to our hospital for fatigue, decreased muscle strength and severe headache reported after the cessation of rhGH treatment for a GH deficiency diagnosed at the age of 2 years and 3 months. Magnetic resonance imaging (MRI) showed an adenohypophyseal hypoplasia with a lack of posterior pituitary hyperintensity, whereas MRI angiography indicated the absence of a normal flow void in the left ICA. Endocrinological tests confirmed the GH deficiency (GH peak after growth-hormone-releasing hormone (GHRH) + arginine: 2.42 ng/mL) with a very low IGF-I value (31 ng/mL) and normal function of other pituitary axes. CONCLUSION: To the best of our knowledge this is the first confirmed case of an isolated GH deficiency in a patient with ICA agenesis. The presence of an isolated pituitary deficit is unlike to be considered only as an effect of hemodynamic mechanism, suggesting a role for genetic factor(s) as a common cause of these two rare birth defects. Further studies could clarify this issue and the underlying mechanisms to better understand the etiopathogenetic characteristics of this disorder.
Assuntos
Artéria Carótida Interna/patologia , Nanismo Hipofisário/complicações , Hormônio do Crescimento Humano/deficiência , Adolescente , Humanos , Imageamento por Ressonância Magnética , Masculino , PrognósticoRESUMO
BACKGROUND: Deletion of the subtelomeric region of 1p36 is one of the most common subtelomeric deletion syndromes. In monosomy 1p36, the presence of obesity is poorly defined, and glucose metabolism deficiency is rarely reported. However, the presence of a typical Prader-Willi-like phenotype in patients with monosomy 1p36 is controversial. CASE PRESENTATION: In this report, we describe two female patients, one who is 6 years 2 months of age and another who is 10 years 1 month of age, both referred to our hospital for obesity and a Prader-Willi-like phenotype. These patients presented with severe obesity (body mass index [BMI] was 26.4 and 27.7, respectively), hyperphagia and developmental delay. Analysis of basal hormone levels showed normal thyroid function and adrenal function but considerable basal hyperinsulinism (the insulin levels were 54.5 and 49.2 µU/ml, respectively). In patient 1, glycaemia was 75 mg/dl (HOMA-R 10.09), and the HbA1c level was 6.1%; in patient 2, glycaemia was 122 mg/dl, and the HbA1c level was 6.6% (HOMA-R 14.82). An oral glucose tolerance test demonstrated impaired glucose tolerance and diabetes mellitus with marked insulin resistance (the peak insulin level for each patient was 197 and 279 µU/mL, respectively, while the 120' insulin level of each patient was 167 and 234 µU/mL, respectively). CONCLUSION: some patients with monosomy 1p36 may show Prader-Willi-like physical and physiologic characteristics such as obesity and hyperinsulinism with impaired glucose metabolism, which can cause type II diabetes mellitus. Further studies are necessary to evaluate these findings.
Assuntos
Transtornos Cromossômicos/complicações , Diabetes Mellitus Tipo 2/etiologia , Hiperglicemia/etiologia , Hiperinsulinismo/complicações , Fenótipo , Síndrome de Prader-Willi/complicações , Criança , Deleção Cromossômica , Cromossomos Humanos Par 1 , Diabetes Mellitus Tipo 2/sangue , Feminino , Humanos , Hiperglicemia/sangueRESUMO
BACKGROUND: A higher prevalence of coeliac disease (CD) has been reported in patients with Williams-Beuren syndrome (WBS), though coexistence with other autoimmune diseases has not been evaluated. OBJECTIVE: The aim of this study was to examine the prevalence of the more frequent autoimmune diseases and organ- and non-organ specific autoantibodies in WBS. METHODS: We longitudinally analysed 46 WBS patients to evaluate the prevalence and co-occurrence of the major autoantibodies and HLA typing for CD diagnosis. These data were compared with healthy age- and sex-matched controls and Down (DS) and Turner (TS) syndrome patients. RESULTS: CD was diagnosed in one (2.2%) WBS patient; this differed significantly from DS and TS (respectively, 10.5% and 9.4%; P < 0.005) but not from healthy controls (0.6%; P = NS). However, no patients with WBS showed anti-thyroid antibodies or other organ- and non-organ specific autoantibodies, which differed significantly from DS (respectively, 10.5% and 7.0%; P < 0.005) and TS (respectively, 9.4% and 9.3%; P < 0.005) patients but not from healthy controls (1.1% and 2.3%). The frequencies of CD-specific HLA-DQ heterodimers were not significantly higher than controls, even though the WBS patients more frequently carried the DQA1*0505 allele (57% vs. 39%; P < 0.05). CONCLUSIONS: CD may not be more frequent in patients with WBS. In fact, no evidence of a significantly higher prevalence of other autoimmune diseases or positivity of the main organ and non-organ specific autoantibodies was found in WBS, such as showed in the healthy controls and unlike by the patients with Turner or Down syndrome. This should prompt us to better understand the occurrence of CD in WBS. Other studies or longer follow-up might be useful to clarify this issue.
Assuntos
Doenças Autoimunes/etiologia , Doença Celíaca/etiologia , Síndrome de Williams/complicações , Síndrome de Williams/imunologia , Adolescente , Autoanticorpos/imunologia , Criança , Síndrome de Down/complicações , Feminino , Antígenos HLA-DR/imunologia , Humanos , Masculino , Prevalência , Risco , Adulto JovemRESUMO
BACKGROUND: Trisomy 9p is an uncommon anomaly characterised by mental retardation, head and facial abnormalities, congenital heart defects, kidney abnormalities, and skeletal malformations. Affected children may also show growth and puberty retardation with delayed bone age. Auxological and endocrinological data are lacking for this syndrome. METHODS: We describe three girls and one boy with 9p trisomy showing substantial growth failure, and we evaluate the main causes of their short stature. RESULTS: The target height was normal in all families, ranging from 0.1 and -1.2 standard deviation scores (SDS). The patients had a low birth-weight (from -1.2 to -2.4 SDS), birth length (from -1.1 to -3.2 SDS), and head circumference (from -0.5 to -1.6 SDS). All patients presented with substantial growth (height) retardation at the time of 9p trisomy diagnosis (from -3.0 to -3.8 SDS).The growth hormone stimulation test revealed a classic growth hormone (GH) deficiency (GHD) in patients 1, 3, and 4. In contrast, patient 2 was determined to have a GH neurosecretory dysfunction (GHNSD). The plasma concentrations of IGF-I and IGFBP-3 were low in all patients for their ages and sexes (from -2.0 to -3.4 SDS, and from -1.9 to -2.8 SDS, respectively).The auxological follow-up showed that those patients who underwent rhGH treatment exhibited a very good response to the GH therapy, whereas patients 3 and 4, whose families chose not to use rhGH treatment, did not experience any significant catch-up growth. CONCLUSIONS: GH deficiency appears to be a possible feature of patients with 9p trisomy syndrome. These patients, particularly those with growth delays, should be evaluated for GH secretion.
RESUMO
Children with chronic illnesses such as Juvenile Idiopathic Arthritis and Crohn's disease, particularly when taking glucocorticoids, are at significant risk for bone fragility. Furthermore, when childhood illness interferes with achieving normal peak bone mass, life-long fracture risk is increased. Osteopenia and osteoporosis, which is increasingly recognized in pediatric chronic disease, likely results from numerous disease- and treatment-related factors, including glucocorticoid exposure. Diagnosing osteoporosis in childhood is complicated by the limitations of current noninvasive techniques such as DXA, which despite its limitations remains the gold standard. The risk:benefit ratio of treatment is confounded by the potential for spontaneous restitution of bone mass deficits and reshaping of previously fractured vertebral bodies. Bisphosphonates have been used to treat secondary osteoporosis in children, but limited experience and potential long-term toxicity warrant caution in routine use. This article reviews the factors that influence loss of normal bone strength and evidence for effective treatments, in particular in patients with gastrointestinal and rheumatologic disorders who are receiving chronic glucocorticoid therapy.
Assuntos
Glucocorticoides/efeitos adversos , Osteoporose/induzido quimicamente , Conservadores da Densidade Óssea/uso terapêutico , Cálcio/uso terapêutico , Criança , Doença Crônica , Doença de Crohn/tratamento farmacológico , Doença de Crohn/epidemiologia , Fraturas Ósseas/prevenção & controle , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/epidemiologia , Osteoporose/tratamento farmacológico , Osteoporose/epidemiologia , Doenças Reumáticas/tratamento farmacológico , Doenças Reumáticas/epidemiologia , Vitamina D/uso terapêuticoRESUMO
Background: Craniopharyngioma (CP), although slow growing and histologically benign, has high morbidity, mostly related to hypothalamus-pituitary dysfunction and electrolyte imbalance. Increased risk of vascular complications has been described. However, data are still poor, especially in the paediatric population. The aim of our study was to evaluate the occurrence, timing, and predisposing factors of deep venous thrombosis (DVT) and other vascular alterations in neurosurgical paediatric CP patients. Materials and Methods: In a single-centre, retrospective study, we investigated 19 CP patients (11 males, 8 females, mean age 10.5 ± 4.3 years), who underwent neurosurgery between December 2016 and August 2022, referred to Meyer Children's Hospital IRCCS in Florence. Results: Five patients (26.3%) presented vascular events, which all occurred in connection with sodium imbalances. Three DVT (two with associated pulmonary embolism, in one case leading to death) developed in the post-operative period, most frequently at 7-10 days. Elevated D-dimers, a reduced partial activated thrombin time and a prolonged C-reactive protein increase were highly related to thrombotic vascular events. One case of posterior cerebral artery pseudoaneurysm was described soon after neurosurgery, requiring vascular stenting. Superficial vein thrombophlebitis was a late complication in one patient with other predisposing factors. Conclusion: CP patients undergoing neurosurgery are at risk of developing DVT and vascular alterations, thus careful follow-up is mandatory. In our study, we found that the phase of transition from central diabetes insipidus to a syndrome of inappropriate antidiuretic hormone secretion may be a period of significant risk for DVT occurrence. Careful vascular follow-up is mandatory in CP-operated patients.
Assuntos
Craniofaringioma , Neoplasias Hipofisárias , Complicações Pós-Operatórias , Humanos , Craniofaringioma/cirurgia , Craniofaringioma/complicações , Feminino , Masculino , Criança , Estudos Retrospectivos , Neoplasias Hipofisárias/cirurgia , Neoplasias Hipofisárias/complicações , Adolescente , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Trombose Venosa/etiologia , Trombose Venosa/epidemiologia , Procedimentos Neurocirúrgicos/efeitos adversos , Pré-Escolar , Doenças Vasculares/etiologia , Doenças Vasculares/epidemiologia , Doenças Vasculares/patologia , SeguimentosRESUMO
PURPOSE: To identify cut-off for basal LH levels and for pelvic ultrasound uterine and ovarian parameters indicating an Hypotalamic-Pituitary-Gonadal (HPG) axis activation as diagnostic of Central Precocious Puberty (CPP). METHODS: 248 girls referred for suspected precocious/early puberty who had undergone a GnRH stimulation test were enrolled and divided into three groups: Premature Idiopathic Thelarche (PIT), CPP, and Early Puberty (EA). For every patient basal serum Luteinising Hormone (LH) and Follicle Stimulating Hormone (FSH), basal LH/FSH ratio and pelvic ultrasonographic parameters were also collected. Through the use of Receiver Operating Curves (ROCs) the sensitivity (Se) and specificity (Sp) of basal LH, FSH, LH/FSH ratio and ultrasonographic parameters were evaluated at each level and Area Under the Curve (AUC) was measured. RESULTS: Basal LH model ≥0.14 mIU/mL reached the highest predictability (90.6% and 78.2%, Se and Sp, respectively). Basal LH/FSH ratio ≥0.1 showed a sensitivity of 85.90% and a specificity of 78.14%, while basal FSH cut-off (≥2.36 mIU/mL) had the lowest predictability, with a less favourable sensitivity (71%) and specificity (70.5%). Cut-off point for uterine length as 35 mm, (83.5% and 42.9% of Se and Sp, respectively) was calculated. For ovarian volumes, ROC curves showed very low sensitivity and specificity. CONCLUSION: A single basal LH measurement under the cut-off limit may be adequate to exclude an HPG axis activation as CPP.
Assuntos
Hormônio Foliculoestimulante , Hormônio Luteinizante , Puberdade Precoce , Humanos , Puberdade Precoce/sangue , Puberdade Precoce/diagnóstico , Feminino , Hormônio Luteinizante/sangue , Criança , Hormônio Foliculoestimulante/sangue , Sensibilidade e Especificidade , Ultrassonografia , Ovário/diagnóstico por imagem , Útero/diagnóstico por imagem , Pré-Escolar , Programas de Rastreamento/métodos , Curva ROCRESUMO
Adiposity rebound (AR) refers to the second rise of the body mass index (BMI) curve that usually occurs between six and eight years of age. AR timing has a significant impact on patients' health: early AR (EAR), usually before the age of five, is considered to be the earliest indicator of obesity and its related health conditions later in life. Many studies have evaluated factors that can be predictors of EAR, and identified low birth weight and gestational weight gain as novel predictors of EAR, highlighting the role of the intrauterine environment in the kinetics of adiposity. Furthermore, children with breastfeeding longer than 4 months have been found to be less likely to have an EAR, whereas children born to advanced-age mothers, high maternal BMI had a higher risk of having an EAR. Some differences were found in the timing of AR in boys and girls, with girls being more likely to have EAR. The aim of this review is to answer the following three questions: 1) Which are the prenatal and perinatal factors associated with increased risk of EAR? Is gender one of these? 2) Which are the outcomes of EAR in childhood and in adulthood? 3) Which measures can be taken in order to prevent premature AR?