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There is a current understanding of type 1 diabetes (T1D) as being the result of a heterogeneous disease of whole pancreas. So far, descriptions of pancreas alterations suggested a global involvement of inflammation throughout the organ, characterized by abnormal age-specific patterns (i.e. > or 0.05) decrease of PI (0.6±0.2 vs 1.1±0.3 mL/kg, p0.05). PVTAIL positively correlated with CPEPEST and CPEPBASAL at Δ+3 months (R=0.55, p=0.002; R=0.47, p0.05). PVBODY did not correlate with any pancreatic function. Finally, we identified multivariate models that included PV and predicted pancreatic endocrine function at Δ+6 and +12 months (i.e. IDAA1C, HbA1C). MRI performed early after T1D onset helped us define specific pancreas alterations and demonstrate for the first time: (1) the increased pancreas atrophy in prepubertal children; (2) correlations between pancreatic subregion volumes and their respective residual functions early after diagnosis and (3) the improvement of endocrine function prediction models by adding PV estimates as predictors. (1) Wentworth et al. 2019;62(1): 33–40 Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Sunday, June 12, 2022 1:00 p.m. - 1:05 p.m.

Involution of a rapidly involuting congenital hemangioma is an unknown cause of neonatal ascites. As involution phase is completed by 14 months after birth, conservative management with diuretics and drainage is possible and may avoid surgical resection.

Arteriovenous malformations (AVMs) are fast-flow lesions that may be destructive and are the most difficult-to-treat vascular anomalies. Embolization followed by surgical resection is commonly used; however, complete resection is rarely possible and partial resection often leads to dramatic worsening. Accumulating data implicate abnormal angiogenic activity in the development of AVMs. Thalidomide has been reported as an inhibitor of vascular proliferation. Here, we report a prospective experimental observational study testing the effects of the angiogenesis inhibitor thalidomide on 18 patients with a severely symptomatic AVM that is refractory to conventional therapies. All patients experienced a rapid reduction in pain, cessation of bleeding, and ulcer healing. Cardiac failure resolved in all three affected patients. Reduced vascularity on arteriography was observed in two patients. One AVM appeared to be cured after 19 months of thalidomide and an 8-year follow-up. Eight AVMs were stable after a mean thalidomide cessation of 58 months, and four lesions recurred after 11.5 months. Combined treatment with embolization permitted dose reduction in five patients with clinical improvement. Grade 3 side effects were dose dependent, including asthenia (n = 2) and erythroderma (n = 2). The results suggest that thalidomide is efficacious in the management of chronic pain, bleeding and ulceration of extensive AVMs that are refractory to conventional therapy. Further clinical study is needed to confirm the safety and efficacy of thalidomide treatment in AVM.

Although the prognosis of CHARGE syndrome can be highly variable from mild until severe, final diagnosis is difficult to establish in utero. The aim of our study is to compare antenatal and postnatal findings in a retrospective cohort of 10 successive patients with a positive CHD7 gene variant in order to identify the specific prenatal features for CHARGE syndrome diagnosis. Fetal ultrasound, follow-up and supplementary investigations are collected and compared to postnatal findings. Congenital heart defect (7/10), choanal atresia (7/10) and tracheoesophageal atresia (4/10) are the most frequent fetal anomalies found. Inner and external ear anomalies appear as the keystone (constant features) for prenatal diagnosis of CHARGE syndrome in fetuses with multiple anomalies and normal microarray karyotype. External ear malformations are identified in all cases by 3D ultrasound when carefully evaluated. MRI and temporal bone CT-Scan are second line useful tools to assess the diagnosis when looking for semicircular canal agenesis, arhinencephaly and/or choanal atresia. Before availability of prenatal exome sequencing in clinical routine, present findings lead to the recommendation that fetuses, with congenital heart defect (mainly septal and conotruncal), cleft lip/palate or unexplained polyhydramnios should carefully be screened for clues suggesting CHARGE syndrome using 2D and 3D ultrasound, MRI and temporal bone CT-Scan. When CHARGE syndrome is suspected with normal molecular karyotype, CHD7 gene sequencing must be offered.

Cirrhosis in adults is associated with modifications of systemic and liver hemodynamics, whereas little is known about the pediatric population. The aim of this work was to investigate whether alterations of hepatic and systemic hemodynamics were correlated with cirrhosis severity in children. The impact of hemodynamic findings on surgical management in pediatric living donor liver transplantation (LT) was evaluated. Liver and systemic hemodynamics were studied prospectively in 52 children (median age, 1 year; 33 with biliary atresia [BA]). The hemodynamics of native liver were studied preoperatively by Doppler ultrasound and intraoperatively using invasive flowmetry. Portosystemic gradient was invasively measured. Systemic hemodynamics were studied preoperatively by Doppler transthoracic echocardiography and intraoperatively by using transpulmonary thermodilution. Hemodynamic parameters were correlated with Pediatric End-Stage Liver Disease (PELD) score and the histological degree of fibrosis (collagen proportionate area [CPA]). Cirrhosis was associated with a 60% reduction of pretransplant total liver flow (n = 46; median, 36 mL/minute/100 g of liver) compared with noncirrhotic livers (n = 6; median, 86 mL/minute/100 g; P = 0.002). Total blood flow into the native liver was negatively correlated with PELD (P

“Serpentine-like syndrome” is a severe and rare association of multiple congenital malformations, characterised by brachioesophagus, secondary intrathoracic stomach, and vertebral anomalies. Other associated anomalies have been described, such as malposition and herniation of abdominal organs. We report the natural history of a baby girl born at 29 weeks of gestation with intra uterine growth restriction, short neck, large rachischisis from cervical to thoracic spine, a very short oesophagus, thoracic stomach associated with a midline diaphragmatic hernia, malrotated gut and median cleft lip. Most of these anomalies were detected antenatally. Molecular karyotype was normal. She died at age 12 days. To our knowledge, the present patient represents the 8th report of a case of “Serpentine-like syndrome”. Brachioesophagus and congenital vertebral anomalies, in particular rachischisis, are the cardinal features of this condition. All reported cases have been sporadic and the cause is still unknown. We believe that the specificity of the presentation as well as the similarities between available descriptions of patients suggests a common, yet to identify, molecular cause, possibly involving a developmental “toolkit”/homeobox gene or related pathways.

Malformations of cortical development (MCD) represent a large group of brain cortical anomalies characterized by distinctive MRI findings. This 'radiologically-based' classification required re evaluation over time on identified underlying mechanisms (cytogenetic and/or molecular). The understanding of genotype findings (nature of cytogenetic/molecular mutation, cellular pathways consequences, timing, …) draw line of evidence on these distinctive group of conditions whereas sometimes precise and constant recurrent genotype/phenotype correlation may not be present. The clinical diagnosis of MCD is often difficult due to variability and rarity of individual types of malformations. Recent studies have established a relationship between lissencephaly and pathogenic variants in genes involved in the kinesin/tubulin pathways, as the KIF5C gene. Pathogenic variants in the KIF5C gene are a more recently discovered cause of severe developmental delay with epilepsy, characterized by specific malformation of cortical development such as pachygyria. Only seven children have been described to date. We report the natural history of a sixteen years old patient identified carrier of a KIF5C gene mutation who developed infantile epilepsy. We then gather phenotype description and molecular results of all reported patients so far in order to better define this entity.

Copyright © 2019 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited, Regenerative medicine using stem cell technology is an emerging field that is currently tested for inborn and acquired liver diseases. Objective. This phase I/II prospective, open label, multicenter, randomized trial aimed primarily at evaluating the safety of Heterologous Human Adult Liver–derived Progenitor Cells (HepaStem) in pediatric patients with urea cycle disorders (UCDs) or Crigler-Najjar (CN) syndrome 6 months posttransplantation. The secondary objective included the assessment of safety up to 12 months postinfusion and of preliminary efficacy. Methods. Fourteen patients with UCDs and 6 with CN syndrome were divided into 3 cohorts by body weight and intraportally infused with 3 doses of HepaStem. Clinical status, portal vein hemodynamics, morphology of the liver, de novo detection of circulating anti– human leukocyte antigen antibodies, and clinically significant adverse events (AEs) and serious adverse events to infusion were evaluated by using an intent-to-treat analysis. Results. The overall safety of HepaStem was confirmed. For the entire study period, patient-month incidence rate was 1.76 for the AEs and 0.21 for the serious adverse events, of which 38% occurred within 1 month postinfusion. There was a trend of higher events in UCD as compared with CN patients. Segmental left portal vein thrombosis occurred in 1 patient and intraluminal local transient thrombus in a second patient. The other AEs were in line with expectations for catheter placement, cell infusion, concomitant medications, age, and underlying diseases. Conclusions. This study led to European clinical trial authorization for a phase II study in a homogeneous patient cohort, with repeated infusions and intermediate doses.

Vascular anomalies, which are broadly identified as "angiomas", are rare entities and often unknown by the medical sphere. They are divided in two different categories which carry different prognosis and management: "vascular tumors" and "vascular malformations". Their precise identification is crucial and involves a good knowledge of the biological classification published by Mulliken and Glowacki and that has recently been updated by the International Society for the Study of Vascular Anomalies (ISSVA). Vascular tumors are benign, common, inborn or not and most of the time disappear with growth. Vascular malformations are always congenital and growth with the child. They can involve type of vessels solely or combined with others. A rheologic differentiation between slow and fast flow malformations is essential in order to characterize the seriousness of the lesion. Frequently, their diagnosis is clinically established and the anamnesis is conducted to answer three questions that are the time of revelation of the lesion ("When?"), its aspect ("What?") and its evolution ("How?"). Further investigations are usually not required but a non-invasive imaging technique such as Doppler ultrasound could be useful if a doubt exists. Surgery is not mandatory and must always be well thought because its consequences might be disastrous. It must be left to cosmetic sequelae of these lesions or to lesions that are totally resectable without causing any unacceptable deformation.

Ultrasound is well suited for examining the pediatric duodenum, given the small size of the patients, the lack of ionizing radiation and high-resolution imaging potential. Technical considerations, normal anatomy, congenital and acquired pathology of the duodenum, and the advantages and limitations of US are discussed and illustrated in this review.

OBJECTIVES: Cirrhotic children wait-listed for liver transplant are prone to bleeding from gastrointestinal varices. Grade 2-3 esophageal varices, red signs, and gastric varices are well-known risk factors. However, the involvement of hemostatic factors remains controversial because of the rebalanced state of coagulation during cirrhosis. METHODS: Children suffering from decompensated cirrhosis were prospectively included while being on waitlist. Portal hypertension was assessed by ultrasound and endoscopy. Coagulopathy was evaluated through conventional tests, thromboelastometry, and platelet function testing. The included children were followed up until liver transplantation, and all bleeding episodes were recorded. Children with or without bleeding were compared according to clinical, radiological, endoscopic, and biological parameters. In addition, validation of a predictive model for risk of variceal bleeding comprising of grade 2-3 esophageal varices, red spots, and fibrinogen level

Background Extensive and complex vascular malformations often cause chronic pain and severe functional restraint. Conventional treatments, such as surgery and/or sclerotherapy, are rarely curative, underscoring the great need for new therapeutic modalities. Recent preclinical and clinical data demonstrated that sirolimus could offset the progression of vascular malformations and significantly improve quality of life of patients through inhibition of the Phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian Target of Rapamycin (mTOR) pathway. The purpose of this prospective study was to assess the efficacy and safety of this treatment in patients with extensive or complex slow-flow vascular malformations. Methods Sirolimus was administered orally on a continuous dosing schedule with pharmacokinetic-guided target serum concentration level of 10 to 15 ng/ml. Patients were seen every month for the first three months and subsequently every three months. The primary endpoints were safety and efficacy, based on clinical, biological and radiological evaluations, as well as a quality of life questionnaire. Results Nineteen patients, from 3 to 64 years old, with lymphatic (LM), venous (VM) or complex slow-flow malformations, refractory to standard care, were enrolled and received sirolimus continuously. After 12 months of follow-up, 16 patients were available for assessment of efficacy and safety: all had a significant and rapid improvement of their symptoms and quality of life. In two patients, sirolimus treatment permitted sclerotherapy and surgery, initially evaluated unfeasible. Sirolimus was well tolerated, with mucositis as the most common (10% of patients) grade 3 adverse event. Conclusions Sirolimus was efficient in extensive LM, VM and/or complex malformations that were refractory to conventional treatments and was well tolerated.

International audience; Mutations in the oligophrenin 1 gene (OPHN1) have been identified in patients with X-linked intellectual disability (XLID) associated with cerebellar hypoplasia and ventriculomegaly, suggesting it could be a recognizable syndromic intellectual disability (ID). Affected individuals share additional clinical features including speech delay, seizures, strabismus, behavioral difficulties, and slight facial dysmorphism. OPHN1 is located in Xq12 and encodes a Rho-GTPase-activating protein involved in the regulation of the G-protein cycle. Rho protein members play an important role in dendritic growth and in plasticity of excitatory synapses. Here we report on 17 individuals from four unrelated families affected by mild to severe intellectual disability due to OPHN1 mutations without cerebellar anomaly on brain MRI. We describe clinical, genetic and neuroimaging data of affected patients. Among the identified OPHN1 mutations, we report for the first time a missense mutation occurring in a mosaic state. We discuss the intrafamilial clinical variability of the disease and compare our patients with those previously reported. We emphasize the power of next generation techniques (X-exome sequencing, whole-exome sequencing and targeted multi-gene panel) to expand the phenotypic and mutational spectrum of OPHN1-related ID.

We herein report the case of a 3-year-old girl with atypical congenital right upper limb lymphedema who developed an angiosarcoma. Only a few cases have been reported following congenital form of lymphedema and only 4 in such a young child. We also summarize all cases of angiosarcoma associated with congenital lymphedema reported in the literature., info:eu-repo/semantics/published

To evaluate the outcome of pediatric living donor liver transplantation (LDLT) regarding portal vein (PV) reconstruction, ABO compatibility, and impact of maternal donation on graft acceptance.LDLT and ABO-mismatched transplantation constitute feasible options to alleviate organ shortage in children. Vascular complications of portal hypoplasia in biliary atresia (BA) and acute rejection (AR) are still major concerns in this field.Data from 250 pediatric LDLT recipients, performed at Cliniques Universitaires Saint-Luc between July 1993 and June 2012, were collected retrospectively. Results were analyzed according to ABO matching and PV complications. Uni- and multivariate analyses were performed to study the impact of immunosuppression, sex matching, and maternal donation on AR rate.Overall, the 10-year patient survival rate was 93.2%. Neither patient or graft loss nor vascular rejection, nor hemolysis, was encountered in the ABO nonidentical patients (n = 58), provided pretransplant levels of relevant isoagglutinins were below 1/16. In BA recipients, the rate of PV complications was lower after portoplasty (4.6%) than after truncal PV anastomosis (9.8%) and to jump graft interposition (26.9%; P = 0.027). In parental donation, maternal grafts were associated with higher 1-year AR-free survival (55.2%) than paternal grafts (39.8%; P = 0.041), but only in BA patients.LDLT, including ABO-mismatched transplantation, constitutes a safe and efficient therapy for liver failure in children. In BA patients with PV hypoplasia, portoplasty seems to constitute the best technique for PV reconstruction. Maternal donation might be a protective factor for AR.

WOS: 000372165300007 PubMed ID: 26951490 Spondyloenchondrodysplasia is a rare immuno-osseous dysplasia caused by biallelic mutations in ACP5. We aimed to provide a survey of the skeletal, neurological and immune manifestations of this disease in a cohort of molecularly confirmed cases. We compiled clinical, genetic and serological data from a total of 26 patients from 18 pedigrees, all with biallelic ACP5 mutations. We observed a variability in skeletal, neurological and immune phenotypes, which was sometimes marked even between affected siblings. In total, 22 of 26 patients manifested autoimmune disease, most frequently autoimmune thrombocytopenia and systemic lupus erythematosus. Four patients were considered to demonstrate no clinical autoimmune disease, although two were positive for autoantibodies. In the majority of patients tested we detected upregulated expression of interferon-stimulated genes (ISGs), in keeping with the autoimmune phenotype and the likely immune-regulatory function of the deficient protein tartrate resistant acid phosphatase (TRAP). Two mutation positive patients did not demonstrate an upregulation of ISGs, including one patient with significant autoimmune disease controlled by immunosuppressive therapy. Our data expand the known phenotype of SPENCD. We propose that the OMIM differentiation between spondyloenchondrodysplasia and spondyloenchondrodysplasia with immune dysregulation is no longer appropriate, since the molecular evidence that we provide suggests that these phenotypes represent a continuum of the same disorder. In addition, the absence of an interferon signature following immunomodulatory treatments in a patient with significant autoimmune disease may indicate a therapeutic response important for the immune manifestations of spondyloenchondrodysplasia. Academy of Medical Sciences (AMS) [AMS-SGCL11-Briggs]

Background : Cerebral folate transporter deficiency caused by FOLR-1 mutations has been described in 2009. This condition is characterized by a 5MTHF level

The online version of the original article can be found at http://dx.doi.org/10.1007/s10875-016-0252-y .

Les malformations veineuses se caracterisent par des ectasies veineuses avec une deficience relative en muscle lisse. Elles sont souvent responsables de deformation, douleur, coagulopathie et saignement. Malgre des sclerotherapies recidivantes et des resections chirurgicales, les recidives sont frequentes. La rapamycine est un inhibiteur de mTor qui cible la cause des malformations veineuses, a savoir la voie de signalisation PI3K-AKT. Les resultats initiaux demontrent que cette nouvelle therapie diminue la douleur, les saignements et la coagulopathie, et ameliore la qualite de vie des patients. Une etude multicentrique europeenne de phase 3 (VASE) a ete mise en route en janvier 2016 pour objectiver les benefices et risques de cette pathologie et determiner quelles malformations sont les plus a meme de repondre positivement a cette medication. Actuellement, pres de 40 patients ont deja ete inclus avec des resultats toujours aussi satisfaisants au niveau de la symptomatologie meme si le volume de la malformation ne diminue pas beaucoup.