A child without kneecaps

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Elevated creatine kinase is mainly harmless in children but persistent and severe hyperCKaemia should raise suspicions of serious muscle damage

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Juvenile xanthogranuloma: A possible diagnostic criterion for Neurofibromatosis type 1 in young children

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Burosumab for X-linked hypophosphatemia in children and adolescents: opinion based on early experience in seven European countries

Given the relatively recent introduction of burosumab in the management of X-linked hypophosphatemia (XLH), there is limited real-world data to guide its use in clinical practice. As a group of European physicians experienced with burosumab treatment in clinical practice, we convened with the objective of sharing these practice-based insights on the use of burosumab in children and adolescents with XLH. We attended two virtual meetings, then discussed key questions via Within3, a virtual online platform. Points of discussion related to patient selection criteria, burosumab starting dose, dose titration and treatment monitoring. Our discussions revealed that criteria for selecting children with XLH varied across Europe from all children above 1 year to only children with overt rickets despite conventional treatment being eligible. We initiated burosumab dosing according to guidance in the Summary of Product Characteristics, an international consensus statement from 2019 and local country guidelines. Dose titration was primarily guided by serum phosphate levels, with some centers also using the ratio of tubular maximum reabsorption of phosphate to glomerular filtration rate (TmP/GFR). We monitored response to burosumab treatment clinically (growth, deformities, bone pain and physical functioning), radiologically (rickets and deformities) and biochemically (serum phosphate, alkaline phosphatase, 1,25-dihydroxyvitamin D, 25-hydroxyvitamin D, urine calcium-creatinine ratio and TmP/GFR). Key suggestions made by our group were initiation of burosumab treatment in children as early as possible, from the age of 1 year, particularly in those with profound rickets, and a need for clinical studies on continuation of burosumab throughout adolescence and into adulthoo

Medicina di precisione nelle malattie rare: il caso della Neurofibromatosi di tipo 1. Analisi di dati clinici e trascrittomica

Background In the past decade, researchers have endeavored to discover effective drugs for managing plexiform neurofibromas (PNs) associated with neurofibromatosis type 1 (NF1), seeking alternatives to often unsatisfactory surgical interventions. Selumetinib, an oral MEK inhibitor, is a the first drug approved for use in children with NF1 and inoperable, symptomatic PN. Predicting patient responses to Selumetinib remains a challenge. This study aimed to identify a molecular blood signature that could distinguish potential responders from non-responders and facilitate tailored therapies Materials and Methods The study enrolled NF1 patients receiving Selumetinib therapy and conducted extensive monitoring, including clinical assessments and volumetric analysis of PNs through MRI. Selumetinib was provided for compassionate use, and side effects were closely monitored. Additionally, transcriptomic analysis of peripheral blood cells compared patient data before and after treatment with that of healthy controls. Results All patients (13) with NF1 and PNs treated con Selumetinib had significant reductions in PN size, with 35% of patients experiencing tumor shrinkage exceeding 20%. Selumetinib demonstrated a favorable safety profile, with manageable side effects. Transcriptomic analysis identified genes associated with the MEK pathway, showing downregulation of genes such as DUSP6, SPP1, and SIGLEC15 and 16, while genes related to immune response, like CD22 and CD79A, were upregulated Conclusion The findings emphasize the clinical utility of Selumetinib in halting PN growth and shed light on potential mechanisms underlying its effectiveness and side effects. Further research is essential to better understand the immune system's role and develop biomarkers for personalized NF1 treatmentBackground In the past decade, researchers have endeavored to discover effective drugs for managing plexiform neurofibromas (PNs) associated with neurofibromatosis type 1 (NF1), seeking alternatives to often unsatisfactory surgical interventions. Selumetinib, an oral MEK inhibitor, is a the first drug approved for use in children with NF1 and inoperable, symptomatic PN. Predicting patient responses to Selumetinib remains a challenge. This study aimed to identify a molecular blood signature that could distinguish potential responders from non-responders and facilitate tailored therapies Materials and Methods The study enrolled NF1 patients receiving Selumetinib therapy and conducted extensive monitoring, including clinical assessments and volumetric analysis of PNs through MRI. Selumetinib was provided for compassionate use, and side effects were closely monitored. Additionally, transcriptomic analysis of peripheral blood cells compared patient data before and after treatment with that of healthy controls. Results All patients (13) with NF1 and PNs treated con Selumetinib had significant reductions in PN size, with 35% of patients experiencing tumor shrinkage exceeding 20%. Selumetinib demonstrated a favorable safety profile, with manageable side effects. Transcriptomic analysis identified genes associated with the MEK pathway, showing downregulation of genes such as DUSP6, SPP1, and SIGLEC15 and 16, while genes related to immune response, like CD22 and CD79A, were upregulated Conclusion The findings emphasize the clinical utility of Selumetinib in halting PN growth and shed light on potential mechanisms underlying its effectiveness and side effects. Further research is essential to better understand the immune system's role and develop biomarkers for personalized NF1 treatmen

Normal lung function in Angolan children

4nonenoneArigliani, Michele; Canciani, Mario C.; Magnolato, Andrea; Quanjer, Philip H.Arigliani, Michele; Canciani, Mario Canciano; Magnolato, Andrea; Quanjer, Philip H

Three Cases of Bartonella quintana Infection in Children

We present 3 children affected by B. quintana infection treated at the IRCCS Burlo Garofolo of Trieste between March and April 2013. B. quintana infection is rare but it should be suspected in patients with fever and lymphadenopathy who do not respond to conventional antibiotic treatment. All patients had a complete recovery without sequelae or relapses

Clinical and Cytometric Study of Immune Involvement in a Heterogeneous Cohort of Subjects With RASopathies and mTORopathies

RASopathies and mTORopathies are groups of genetic syndromes associated with increased activation of the RAS-MAPK or the PI3K-AKT-mTOR pathway, resulting in altered cell proliferation during embryonic and postnatal development. The RAS-MAPK and the PI3K-AKT-mTOR pathways are connected to each other and play a crucial role in adaptive immunity. However, with the exception of Activated PI3K delta syndrome (APDS), immune function has not been deeply studied in these disorders. We collected clinical and immunophenotypic data of a cohort of patients with RASopathies and mTORopathies. Overall, we enrolled 47 patients (22 females, 25 males, age 2\u201340 years): 33 with neurofibromatosis type 1, 11 Noonan syndrome and 3 Bannayan-Riley-Ruvalcaba syndrome. 8 patients reported a history of invasive infections requiring hospitalization and intravenous antibiotic therapy. Only 3 patients reported a history of unusual, difficult-to-treat or deep-seated infection. Adenotonsillectomy was performed in 11 patients (24%). However, in most cases (83%) patients\u2019 parents did not perceive their child as more prone to infections than their peers. Lymphocyte subpopulations were analyzed in 37 of the 47 patients (16 female, 21 males, age 1\u201340 years). Among the studied lymphocyte subsets, the only consistent alteration regarded an increased percentage of immature B cells (recent bone marrow emigrants) in 34 out of 37 (91,9%) patients, and an increased percentage of double negative T cells in 9 patients. In conclusion, although borderline immune abnormalities were present in a significant proportion of subjects and adenotonsillectomy was performed more frequently than expected for the general population, no major immune disturbance was found in this cohort of patients

Administration of bicarbonates through percutaneous gastrostomy with continuous nocturnal infusion in a patient with Kearns-Sayre disease: a life changing therapeutical paradigm

Abstract Background Mitochondrial diseases (MDs) are systemic disorders that can affect multiple organs. Renal manifestations, including renal tubular acidosis, are common because kidneys are particularly vulnerable to energy deprivation. Treatment of MDs is often complex and electrolyte replacement can be difficult especially in pediatric patients, because large and repeated amounts of oral supplements are needed but are not well tolerated. Case presentation We describe the case of a girl affected by Kearns-Sayre disease with severe renal tubular acidosis. The management of her metabolic acidosis was challenging because she showed persistent low levels of serum bicarbonates despite a progressive incrementation of oral bicarbonates. Furthermore, as a result to the ingestion of large amounts of alkali, the girl developed an aversion to oral supplementation. After positioning a percutaneous gastrostomy (PEG) and starting enteral administration of bicarbonates (with daily boluses and continuous nocturnal infusion), she finally obtained an adequate electrolyte control, with a significant increase in her quality of life. Conclusions In MDs, the combination of nocturnal continuous enteral administration of alkali plus diurnal boluses may represent a valid solution to correct metabolic acidosis. It can also result in an improved patients’ quality of life, particularly in pediatric settings, where compliance to oral therapy is often lacking due to the large and repeated amounts of unpalatable bicarbonates solutions required

When Long-Lasting Food Selectivity Leads to an Unusual Genetic Diagnosis: A Case Report

Hereditary fructose intolerance is an autosomal recessive disorder of fructose metabolism caused by catalytic deficiency of aldolase B enzyme [1]. The disease is typically expressed when fructose- and sucrose-containing foods are first introduced in the diet; acute manifestations include nausea, vomiting, abdominal distress, and symptomatic hypoglycemia [1,2]. Chronic fructose ingestion eventually leads to poor feeding, growth retardation and gradual liver and/or renal failure [3,4]. Some patients may remain undiagnosed until adulthood because of a self-protective avoidance of sweet tasting food that prevents the development of acute toxicity from fructose containing food; however, these subjects may suffer intermittent symptoms throughout life, leading to potentially serious misdiagnosis [4]. We report the case of a patient with unrecognized hereditary fructose intolerance in which chronic gastrointestinal complaints, low body weight, and unexplained food avoidance were addressed as manifestations of an eating disorder during adolescence