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INTRODUCTION: Neurocutaneous syndromes (NCS) are a heterogeneous group of conditions with multiorgan involvement and diverse manifestations, evolving throughout life with significant morbidity. A multidisciplinary approach to NCS patients has been advocated, although a specific model is not yet established. The aim of this study was 1) to describe the organization of the recently created Multidisciplinary Outpatient Clinic of Neurocutaneous Diseases (MOCND) at a Portuguese pediatric tertiary hospital; 2) to share our institutional experience focusing on the most common conditions, neurofibromatosis type 1 (NF1) and tuberous sclerosis complex (TSC); 3) to analyze the advantages of a multidisciplinary center and approach in NCS. METHODS: Retrospective analysis of 281 patients enrolled in the MOCND over the first five years of activity (October 2016 to December 2021), reviewing genetics, family history, clinical features, complications, and therapeutic strategies for NF1 and TSC. RESULTS: The clinic works weekly with a core team of pediatricians and pediatric neurologists supported by other specialties as needed. Of the 281 patients enrolled, 224 (79.7%) had identifiable syndromes such as NF1 (n = 105), TSC (n = 35), hypomelanosis of Ito (n = 11), Sturge-Weber syndrome (n = 5), and others. In NF1 patients, 41.0% had a positive family history, all manifested café-au-lait macules, 38.1% neurofibromas with 45.0% being large plexiform neurofibromas. Sixteen were under treatment with selumetinib. Genetic testing was performed in 82.9% of TSC patients with pathogenic variants found in TSC2 gene in 72.4% patients (82.7% if considered contiguous gene syndrome). Family history was positive in 31.4%. All TSC patients presented hypomelanotic macules and fulfilled diagnostic criteria. Fourteen patients were being treated with mTOR inhibitors. CONCLUSION: Offering a systematic and multidisciplinary approach to NCS patients enables timely diagnosis, promotes a structured follow-up, and encourages discussion to outline management plans for optimal care to every patient, with significant impact on the quality of life of patients and families.
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Síndromes Neurocutáneos , Neurofibromatosis 1 , Humanos , Niño , Portugal , Síndromes Neurocutáneos/diagnóstico , Síndromes Neurocutáneos/terapia , Calidad de Vida , Estudios Retrospectivos , Centros de Atención Terciaria , Instituciones de Atención Ambulatoria , Neurofibromatosis 1/terapiaRESUMEN
BACKGROUND: Associations between anthropometric measures and patient outcomes in children are inconsistent and mainly based on data at kidney replacement therapy (KRT) initiation. We studied associations of height and body mass index (BMI) with access to kidney transplantation, graft failure, and death during childhood KRT. METHODS: We included patients < 20 years starting KRT in 33 European countries from 1995-2019 with height and weight data recorded to the ESPN/ERA Registry. We defined short stature as height standard deviation scores (SDS) < -1.88 and tall stature as height SDS > 1.88. Underweight, overweight and obesity were calculated using age and sex-specific BMI for height-age criteria. Associations with outcomes were assessed using multivariable Cox models with time-dependent covariates. RESULTS: We included 11,873 patients. Likelihood of transplantation was lower for short (aHR: 0.82, 95% CI: 0.78-0.86), tall (aHR: 0.65, 95% CI: 0.56-0.75), and underweight patients (aHR: 0.79, 95%CI: 0.71-0.87). Compared with normal height, patients with short and tall statures showed higher graft failure risk. All-cause mortality risk was higher in short (aHR: 2.30, 95% CI: 1.92-2.74), but not in tall stature. Underweight (aHR: 1.76, 95% CI: 1.38-2.23) and obese (aHR: 1.49, 95% CI: 1.11-1.99) patients showed higher all-cause mortality risk than normal weight subjects. CONCLUSIONS: Short and tall stature and being underweight were associated with a lower likelihood of receiving a kidney allograft. Mortality risk was higher among pediatric KRT patients with a short stature or those being underweight or obese. Our results highlight the need for careful nutritional management and multidisciplinary approach for these patients. A higher resolution version of the Graphical abstract is available as Supplementary information.
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Enanismo , Delgadez , Masculino , Femenino , Niño , Humanos , Delgadez/epidemiología , Delgadez/complicaciones , Obesidad/complicaciones , Índice de Masa Corporal , Terapia de Reemplazo Renal , Sistema de RegistrosRESUMEN
BACKGROUND: Small cohort studies have reported high parathyroid hormone (PTH) levels in patients with Bartter syndrome and lower serum phosphate levels have anecdotally been reported in patients with Gitelman syndrome. In this cross-sectional study, we assessed PTH and phosphate homeostasis in a large cohort of patients with salt-losing tubulopathies. METHODS: Clinical and laboratory data of 589 patients with Bartter and Gitelman syndrome were provided by members of the European Rare Kidney Diseases Reference Network (ERKNet) and the European Society for Paediatric Nephrology (ESPN). RESULTS: A total of 285 patients with Bartter syndrome and 304 patients with Gitelman syndrome were included for analysis. Patients with Bartter syndrome type I and II had the highest median PTH level (7.5 pmol/L) and 56% had hyperparathyroidism (PTH >7.0 pmol/L). Serum calcium was slightly lower in Bartter syndrome type I and II patients with hyperparathyroidism (2.42 versus 2.49 mmol/L; P = .038) compared to those with normal PTH levels and correlated inversely with PTH (rs -0.253; P = .009). Serum phosphate and urinary phosphate excretion did not correlate with PTH. Overall, 22% of patients had low serum phosphate levels (phosphate-standard deviation score < -2), with the highest prevalence in patients with Bartter syndrome type III (32%). Serum phosphate correlated with tubular maximum reabsorption of phosphate/glomerular filtration rate (TmP/GFR) (rs 0.699; P < .001), suggesting renal phosphate wasting. CONCLUSIONS: Hyperparathyroidism is frequent in patients with Bartter syndrome type I and II. Low serum phosphate is observed in a significant number of patients with Bartter and Gitelman syndrome and appears associated with renal phosphate wasting.
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Síndrome de Bartter , Síndrome de Gitelman , Hiperparatiroidismo , Niño , Humanos , Síndrome de Gitelman/complicaciones , Hormona Paratiroidea , Síndrome de Bartter/complicaciones , Estudios Transversales , Fosfatos , Homeostasis , CalcioRESUMEN
Abstract Phosphopenic rickets may be caused by mutations in the PHEX gene (phosphate regulating endopeptidase homolog X-linked). Presently, more than 500 mutations in the PHEX gene have been found to cause hypophosphatemic rickets. The authors report a clinical case of a 4-year-old girl with unremarkable family history, who presented with failure to thrive and bowing of the legs. Laboratory tests showed hypophosphatemia, elevated alkaline phosphatase, normal calcium, mildly elevated PTH and normal levels of 25(OH)D and 1.25(OH)D. The radiological study showed bone deformities of the radius and femur. Clinical diagnosis of phosphopenic rickets was made and the genetic study detected a heterozygous likely pathogenic variant of the PHEX gene: c.767_768del (p.Thr256Serfs*7). This variant was not previously described in the literature or databases. Knowledge about new mutations can improve patient's outcome. Genetic analysis can help to establish a genotype-phenotype correlation.
Resumo O raquitismo fosfopênico pode ser causado por mutações no gene PHEX (ligado ao X do homólogo da endopeptidase que regula o fosfato). Atualmente, mais de 500 mutações no gene PHEX causam raquitismo hipofosfatêmico. Os autores relatam um caso clínico de uma menina de 4 anos com histórico familiar sem relevância, que apresentou falha no crescimento e arqueamento das pernas. Os exames laboratoriais mostraram hipofosfatemia, fosfatase alcalina elevada, cálcio normal, PTH levemente elevado e níveis normais de 25(OH)D e 1,25(OH)D. O estudo radiológico mostrou deformidades ósseas no rádio e no fêmur. O diagnóstico clínico do raquitismo fosfopênico foi realizado e o estudo genético detectou uma provável variante patogênica heterozigótica do gene PHEX: c.767_768del (p.Thr256Serfs*7). Esta variante não foi descrita anteriormente na literatura ou nas bases de dados. O conhecimento sobre novas mutações pode melhorar o desfecho de pacientes. A análise genética pode ajudar a estabelecer uma correlação genótipo-fenótipo.
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Humanos , Femenino , Preescolar , Enfermedades Óseas , Hipofosfatemia , Raquitismo Hipofosfatémico Familiar/diagnóstico , Raquitismo Hipofosfatémico Familiar/genética , Endopeptidasa Neutra Reguladora de Fosfato PHEX/genética , MutaciónRESUMEN
BACKGROUND: Acute tubulointerstitial nephritis (TIN) is a significant cause of acute renal failure in paediatric and adult patients. There are no large paediatric series focusing on the aetiology, treatment and courses of acute TIN. PATIENTS, DESIGN AND SETTING: We collected retrospective clinical data from paediatric patients with acute biopsy-proven TIN by means of an online survey. Members of four professional societies were invited to participate. RESULTS: Thirty-nine physicians from 18 countries responded. 171 patients with acute TIN were included (54% female, median age 12 years). The most frequent causes were tubulointerstitial nephritis and uveitis syndrome in 31% and drug-induced TIN in 30% (the majority of these caused by non-steroidal anti-inflammatory drugs). In 28% of patients, no initiating noxae were identified (idiopathic TIN). Median estimated glomerular filtration rate (eGFR) rose significantly from 31 at time of renal biopsy to 86 mL/min/1.73 m2 3-6 months later (p<0.001). After 3-6 months, eGFR normalised in 41% of patients (eGFR ≥90 mL/min/1.73 m2), with only 3% having severe or end-stage impairment of renal function (<30 mL/min/1.73 m2). 80% of patients received corticosteroid therapy. Median eGFR after 3-6 months did not differ between steroid-treated and steroid-untreated patients. Other immunosuppressants were used in 18% (n=31) of patients, 21 of whom received mycophenolate mofetil. CONCLUSIONS: Despite different aetiologies, acute paediatric TIN had a favourable outcome overall with 88% of patients showing no or mild impairment of eGFR after 3-6 months. Prospective randomised controlled trials are needed to evaluate the efficacy of glucocorticoid treatment in paediatric patients with acute TIN.
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Nefritis Intersticial , Adulto , Niño , Estudios Transversales , Femenino , Humanos , Internet , Masculino , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
OBJECTIVE: Burosumab is an orphan medicinal product (OMP) approved in Europe for the treatment of X-linked hypophosphatemia (XLH). The aim of this study was to assess the value of burosumab versus conventional therapy for the treatment of paediatric XLH, through a multi-criteria decision analysis (MCDA) framework for health technology assessment (HTA) of OMPs in Portugal. METHODS: The MCDA framework considered 14 criteria related to disease burden, therapeutic value and economic burden. A multidisciplinary panel of national stakeholders participated in a two-phase exercise. In the first phase, relative weights and part-worth utilities for the criteria and their levels were elicited and a reimbursement likelihood function was calibrated through adaptive conjoint analysis. In the second phase, burosumab and conventional therapy were assessed against the criteria, providing a global value score (0-100) and reimbursement likelihood (0-100%) for both. RESULTS: Of the 14 criteria, disease burden, therapeutic value and economic burden criteria represented 27.29%, 57.17% and 15.53% of the total weight in the decision, respectively. All disease burden and some therapeutic value criteria, typically not included in traditional HTA, represented 47.88% of the total weight. Burosumab was unanimously considered superior to conventional therapy, with an average (range) global value score of 84.96 (82.48-86.54) against 48.06 (43.37-57.68), and reimbursement likelihood of 97.50% (96.78%-98.32%) against 43.66% (31.48%-68.73%), respectively. CONCLUSIONS: MCDA represents a powerful tool in HTA decision-making for OMPs. The results of this MCDA acknowledge burosumab as a disease-modifying drug, deemed superior to conventional therapy for the treatment of paediatric XLH.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Raquitismo Hipofosfatémico Familiar , Producción de Medicamentos sin Interés Comercial , Niño , Técnicas de Apoyo para la Decisión , Raquitismo Hipofosfatémico Familiar/tratamiento farmacológico , Humanos , Evaluación de la Tecnología BiomédicaRESUMEN
Phosphopenic rickets may be caused by mutations in the PHEX gene (phosphate regulating endopeptidase homolog X-linked). Presently, more than 500 mutations in the PHEX gene have been found to cause hypophosphatemic rickets. The authors report a clinical case of a 4-year-old girl with unremarkable family history, who presented with failure to thrive and bowing of the legs. Laboratory tests showed hypophosphatemia, elevated alkaline phosphatase, normal calcium, mildly elevated PTH and normal levels of 25(OH)D and 1.25(OH)D. The radiological study showed bone deformities of the radius and femur. Clinical diagnosis of phosphopenic rickets was made and the genetic study detected a heterozygous likely pathogenic variant of the PHEX gene: c.767_768del (p.Thr256Serfs*7). This variant was not previously described in the literature or databases. Knowledge about new mutations can improve patient's outcome. Genetic analysis can help to establish a genotype-phenotype correlation.
Asunto(s)
Enfermedades Óseas , Raquitismo Hipofosfatémico Familiar , Hipofosfatemia , Preescolar , Raquitismo Hipofosfatémico Familiar/diagnóstico , Raquitismo Hipofosfatémico Familiar/genética , Femenino , Humanos , Mutación , Endopeptidasa Neutra Reguladora de Fosfato PHEX/genéticaAsunto(s)
Síndrome de Inmunodeficiencia Adquirida/complicaciones , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Terapia Antirretroviral Altamente Activa/efectos adversos , Síndrome Inflamatorio de Reconstitución Inmune/etiología , Microangiopatías Trombóticas/complicaciones , Antibacterianos/uso terapéutico , Diagnóstico Diferencial , Resultado Fatal , Humanos , Síndrome Inflamatorio de Reconstitución Inmune/tratamiento farmacológico , Inmunoglobulinas/uso terapéutico , Lactante , Linfohistiocitosis Hemofagocítica/complicaciones , Linfohistiocitosis Hemofagocítica/tratamiento farmacológico , Masculino , Metilprednisolona/uso terapéutico , Microangiopatías Trombóticas/tratamiento farmacológicoRESUMEN
BACKGROUND: Primary distal renal tubular acidosis (dRTA) is a rare disorder, and we aimed to gather data on treatment and long-term outcome. METHODS: We contacted paediatric and adult nephrologists through European professional organizations. Responding clinicians entered demographic, biochemical, genetic and clinical data in an online form. RESULTS: Adequate data were collected on 340 patients (29 countries, female 52%). Mutation testing had been performed on 206 patients (61%); pathogenic mutations were identified in 170 patients (83%). The median (range) presentation age was 0.5 (0-54) years and age at last follow-up was 11.0 (0-70.0) years. Adult height was slightly below average with a mean (SD score) of -0.57 (±1.16). There was an increased prevalence of chronic kidney disease (CKD) Stage ≥2 in children (35%) and adults (82%). Nephrocalcinosis was reported in 88%. Nephrolithiasis was more common with SLC4A1 mutations (42% versus 21%). Thirty-six percent had hearing loss, particularly in ATP6V1B1 (88%). The median (interquartile range) prescribed dose of alkali (mEq/kg/day) was 1.9 (1.2-3.3). Adequate metabolic control (normal plasma bicarbonate and normocalciuria) was achieved in 158 patients (51%), more commonly in countries with higher gross domestic product (67% versus 23%), and was associated with higher height and estimated glomerular filtration rate. CONCLUSION: Long-term follow-up from this large dRTA cohort shows an overall favourable outcome with normal adult height for most and no patient with CKD Stage 5. However, 82% of adult patients have CKD Stages 2-4. Importance of adequate metabolic control was highlighted by better growth and renal function but was achieved in only half of patients.
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Acidosis Tubular Renal/terapia , Pérdida Auditiva Sensorineural/terapia , Acidosis Tubular Renal/complicaciones , Acidosis Tubular Renal/genética , Adolescente , Adulto , Anciano , Bicarbonatos/sangre , Calcio/orina , Niño , Preescolar , Estudios de Cohortes , Análisis Mutacional de ADN , Sordera/complicaciones , Sordera/genética , Sordera/terapia , Femenino , Estudios de Asociación Genética , Tasa de Filtración Glomerular , Pérdida Auditiva Sensorineural/complicaciones , Pérdida Auditiva Sensorineural/genética , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Mutación , Nefrocalcinosis/complicaciones , Nefrocalcinosis/genética , Nefrocalcinosis/terapia , Enfermedades Raras/complicaciones , ATPasas de Translocación de Protón Vacuolares/genética , Adulto JovenRESUMEN
Tuberous sclerosis(TS) is an autosomal dominant disease caused by mutations in TSC1 and TSC2 genes. TSC2 gene is located in chromosome 16p13.3, adjacent to PKD1 gene, responsible for the autosomal dominant polycystic kidney disease. In a rare subgroup of patients, the presence of a deletion which simultaneously affects the TSC2 and PKD1 genes has been confirmed. TSC2/PKD1-Contiguous Gene Syndrome is characterised by the early appearance of autosomal dominant polycystic kidney disease in combination with several phenotypic manifestations of TS. We present a 13-year-old girl with bilateral renal cysts detected at the age of 9 months. At the age of 13, she was referred to the Dermatology Outpatients Clinic due to a facial cutaneous eruption. She presented with facial erythema, fibroadenomas with malar distribution and disseminated hypomelanotic macules, meeting the criteria for TS. TSC2/PKD1 Contiguous Gene Syndrome deletion was suspected, being later confirmed by genetic testing.
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Riñón Poliquístico Autosómico Dominante/diagnóstico , Esclerosis Tuberosa/diagnóstico , Adolescente , Diagnóstico Diferencial , Femenino , Humanos , Imagen por Resonancia Magnética , Riñón Poliquístico Autosómico Dominante/diagnóstico por imagen , Riñón Poliquístico Autosómico Dominante/genética , Esclerosis Tuberosa/diagnóstico por imagen , Esclerosis Tuberosa/genéticaRESUMEN
INTRODUCTION: Systematic screening for TORCH infections and group B Streptococcus (GBS) during pregnancy has been an important factor in the improvement of perinatal care. AIM: To evaluate TORCH serology and GBS carriers state in the population of a maternity, to assess variability with age and nationality and to search for congenital infections. MATERIAL AND METHODS: Non-probabilistic prevalence study. RESULTS: 9508 TORCH and 2639 GBS results were registered. Immunity rate for rubella was 93.3%, higher for Portuguese women; for toxoplasmosis it was 25.7%, higher among the oldest and foreign women; IgG for CMV was positive in 62.4%, no influence of age was found. VDRL was reactive in 0.5%; HBsAg was found to be positive in 2.3%, higher in foreign women. Antibodies for hepatitis C virus and HIV were found respectively in 1.4% and 0.7%. No congenital infections were diagnosed. GBS carrier state was found in 13.9%. DISCUSSION: A high rate of positive IgG was found for rubella reflecting vaccines policy. For toxoplasmosis the low rate of positives means that a high number of pregnant women have to repeat serology during pregnancy with inherent costs. Like in the general population, a high rate of CMV positive mothers was found. For some infections we found that foreign women had different conditions. CONCLUSION: Knowledge on TORCH and GBS state helps to better draw guidelines concerning screening policies during pregnancy.
Objectivo: Avaliar o resultado de serologias para infeções do grupo TORCH e do rastreio para Streptococcus do grupo B (SGB) numa amostra de grávidas de uma maternidade, estudar a influência da idade e da nacionalidade, e identificar casos de infecção congénita.Material e Métodos: Estudo não probabilístico de prevalência de imunidade e infecção durante a gravidez.Resultados: Registámos 9508 serologias TORCH e 2639 resultados de rastreio para SGB. A taxa de imunidade para rubéola foi 93,3%, significativamente mais elevada em portuguesas; 25,7% das mulheres tinham IgG positiva para Toxoplasma goondii; a taxa foi mais elevada nas mulheres mais velhas e entre estrangeiras; encontrámos IgG positiva para vírus citomegálico humano (CMV) em 62,4%; não houve variação com a idade. O VDRL foi reactivo em 0,5%; 2,3% das mães tinham AgHBs positivo, mais frequente nas estrangeiras; 1,4% tinha anticorpos para o vírus da hepatite C e 0,7% tinha VIH positivo. Não houve casos declarados de infeção congénita; 13,9% das mulheres eram portadoras de SGB.Discussão: A elevada taxa de imunidade para a rubéola é resultado da política nacional de vacinação. A baixa taxa de imunidade para a toxoplasmose torna mais dispendioso o acompanhamento das grávidas. A elevada prevalência do CMV está de acordo com o encontrado na comunidade. Para algumas infeções foram encontradas diferenças de acordo com a nacionalidade.Conclusão: O conhecimento da imunidade e infecção na população é um instrumento importante para o planeamento dos rastreios durante a gravidez.
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Complicaciones Infecciosas del Embarazo/sangre , Complicaciones Infecciosas del Embarazo/inmunología , Infecciones Estreptocócicas/sangre , Infecciones Estreptocócicas/inmunología , Adolescente , Adulto , Portador Sano , Femenino , Humanos , Persona de Mediana Edad , Embarazo , Complicaciones Infecciosas del Embarazo/diagnóstico , Complicaciones Infecciosas del Embarazo/epidemiología , Prevalencia , Estudios Seroepidemiológicos , Infecciones Estreptocócicas/diagnóstico , Infecciones Estreptocócicas/epidemiología , Streptococcus agalactiae/inmunología , Adulto JovenRESUMEN
A 6-month-old girl with Beckwith-Wiedemann syndrome, multiple haemangiomas (axillary, laryngeal, pulmonary and hepatic) and diaphragmatic eventration was reported. All tumours responded to treatment with propranolol. The surgical correction of diaphragmatic eventration was crucial to a better outcome.
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Síndrome de Beckwith-Wiedemann/complicaciones , Eventración Diafragmática/complicaciones , Hemangioma/complicaciones , Neoplasias Primarias Múltiples/complicaciones , Axila , Eventración Diafragmática/cirugía , Femenino , Hemangioma/tratamiento farmacológico , Humanos , Lactante , Neoplasias Laríngeas/complicaciones , Neoplasias Laríngeas/tratamiento farmacológico , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Primarias Múltiples/tratamiento farmacológicoRESUMEN
A 16-year-old boy with a diagnosis of Parkes-Weber syndrome presented with a lower leg discrepancy of 3 cm for orthopaedic management. He had the triad of red skin lesion, lymphoedema and overgrowth of the right leg and multiple arteriovenous fistulae confirmed by angiography. Considering the risk of aggravating the vascular lesion, we decided conservative management of unequal limb lengths as long as this is well tolerated.
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Diferencia de Longitud de las Piernas/terapia , Síndrome de Sturge-Weber/terapia , Adolescente , Diagnóstico Diferencial , Humanos , Imagen por Resonancia Magnética , Masculino , Síndrome de Sturge-Weber/diagnósticoRESUMEN
Bilateral facial palsy (BFP) is a very uncommon entity, particularly in the paediatric age group. Despite its several aetiologies, neuroborreliosis should be suspected, especially in children from endemic areas presenting with acute neurological disease of unknown cause. We present two cases of BFPs as the presenting forms of neuroborreliosis.