PREPL deficiency: delineation of the phenotype and development of a functional blood assay.

PurposePREPL deficiency causes neonatal hypotonia, ptosis, neonatal feeding difficulties, childhood obesity, xerostomia, and growth hormone deficiency. Different recessive contiguous gene deletion syndromes involving PREPL and a variable combination of SLC3A1 (hypotonia-cystinuria syndrome), CAMKMT (atypical hypotonia-cystinuria syndrome), and PPM1B (2p21 deletion syndrome) have been described. In isolated PREPL deficiency, previously described only once, the absence of cystinuria complicates the diagnosis. Therefore, we developed a PREPL blood assay and further delineated the phenotype.MethodsClinical features of new subjects with PREPL deficiency were recorded. The presence of PREPL in lymphocytes and its reactivity with an activity-based probe were evaluated by western blot.ResultsFive subjects with isolated PREPL deficiency, three with hypotonia-cystinuria syndrome, and two with atypical hypotonia-cystinuria syndrome had nine novel alleles. Their IQs ranged from 64 to 112. Adult neuromuscular signs included ptosis, nasal dysarthria, facial weakness, and variable proximal and neck flexor weakness. Autonomic features are prevalent. PREPL protein and reactivity were absent in lymphocytes from subjects with PREPL deficiency, but normal in the clinically similar Prader-Willi syndrome.ConclusionPREPL deficiency causes neuromuscular, autonomic, cognitive, endocrine, and dysmorphic clinical features. PREPL is not deficient in Prader-Willi syndrome. The novel blood test should facilitate the confirmation of PREPL deficiency.

[A real-world study focused on the effectiveness and safety of adalimumab as first-line anti-TNF treatment for pediatric Crohn's disease]. / Efectividad y seguridad en nuestro entorno de adalimumab como tratamiento anti-TNF de primera linea en niños con enfermedad de Crohn.

BACKGROUND AND OBJECTIVES: Adalimumab (ADA), a monoclonal humanised anti-TNF antibody, is usually prescribed as a second-line treatment in paediatric Crohn's disease (CD) patients who have become unresponsive or developed intolerance to infliximab (IFX). In the case series reported, more than 70% of patients had initially been treated with IFX. Data on short- and long-term effectiveness of ADA in anti-TNF naïve patients is limited. The aim of this study is to describe our experience with ADA as a first-line anti-TNF in paediatric CD patients. MATERIAL AND METHODS: This is a multicentre retrospective study including anti-TNF naïve paediatric CD patients treated with ADA as first-line anti-TNF. RESULTS: Sixty-two patients (34males), with a mean age of 13.0±2.4years and a disease duration of 7.3 (IQR 2.7-21) months were included. Median wPCDAI was 35 (IQR 24.3-47.5). Fifty-eight out of 62 (93.5%) were on combo therapy at baseline. Clinical remission at week12 was achieved in 50 out of 62 (80.6%) and in 57 out of 60 (95.0%) at week52. Eight patients (13%) reported adverse events. Mean height, growth rate and BMI z-scores improved significantly between baseline and week 52, especially in patients with growth failure. CONCLUSIONS: ADA treatment leads to lasting clinical remission in anti-TNF naïve paediatric patients with CD. ADA significantly improved growth rate in children with CD who had growth delay at baseline.

Direct percutaneous endoscopic jejunostomy in pediatric age with a pexies triangulation system: report of a case and literature review.

Direct percutaneous endoscopic jejunostomy (DPEJ) is an infrequent procedure as it is not always easy to obtain transillumination, being this the main reason for failure of this technique. In patients with previous surgery, this procedure is more complex and there are only 6 reported cases in pediatric population. In our case, we provide the use of an endoscopic triangulation system with "T" pexies not used before in these cases. With this technique, we guarantee not to replace the introduction system afterwards, obtaining the placement of a balloon fixation system initially. We also provide several improvements that helped us developing the procedure: Placement of the jejunostomy through a gastrostomy; use of water column to avoid penetration in hollow viscus; use of a guide wire, and a triangulation pexy system.