Growth impairment in Japanese children with inflammatory bowel disease: A multicenter prospective cohort study.

Objectives: To investigate the prevalence and characteristics of growth impairment (GI) in children with inflammatory bowel disease (IBD).

Methods: In this prospective observational study, 402 children with ulcerative colitis (UC, n = 257) and Crohn's disease (CD, n = 145) were enrolled from the Japanese Pediatric IBD Registry (2012-2020). GI was defined by Paris classification criteria.

Long-term follow-up and transcatheter embolization of extrahepatic congenital portosystemic shunt with shifting hemodynamics.

Congenital portosystemic shunt (CPSS) is a rare vascular anomaly in which portal vein blood flows into the systemic circulation without passing through the liver. They occur in approximately 1 in 30,000-50,000 live births. We present an 11-year-old patient with an extrahepatic CPSS managed with long-term follow-up.

The Apparent Lack of the Risk of Intussusception Immediately After Rotavirus Vaccination Among Japanese Infants.

Rotavirus vaccines carry a small risk of intussusception mainly 1-7 days after vaccination in the United States of America, Europe, Australia, and Latin America where the background rate of intussusception is relatively low. Such risks are undetectable in Africa and India where the background rate is the lowest. Because few studies were carried out in high-background-rate countries such as Japan, we examined how intussusception occurred in infants living in Akita prefecture, Japan, while the vaccines were sold in the private market.

Familial Episodic Pain Syndrome: A Japanese Family Harboring the Novel Variant c.2431C>T (p.Leu811Phe) in SCN11A.

Familial episodic pain syndrome (FEPS) is an autosomal-dominant inherited disorder characterized by paroxysmal pain episodes. FEPS appears in early childhood, gradually disappearing with age, and pain episodes can be triggered by fatigue, bad weather, and cold temperatures. Several gain-of-function variants have been reported for SCN9A, SCN10A, or SCN11A, which encode the voltage-gated sodium channel α subunits Nav1.

Genetic Analysis of , , and in Familial Episodic Pain Syndrome (FEPS) in Japan and Proposal of Clinical Diagnostic Criteria.

Familial episodic pain syndrome (FEPS) is an early childhood onset disorder of severe episodic limb pain caused mainly by pathogenic variants of , , and , which encode three voltage-gated sodium channels (VGSCs) expressed as key determinants of nociceptor excitability in primary sensory neurons. There may still be many undiagnosed patients with FEPS. A better understanding of the associated pathogenesis, epidemiology, and clinical characteristics is needed to provide appropriate diagnosis and care.

Genetic Ablation of Pyruvate Dehydrogenase Kinase Isoform 4 Gene Enhances Recovery from Hyperoxic Lung Injury: Insights into Antioxidant and Inflammatory Mechanisms.

Background: Pyruvate dehydrogenase kinase isoform 4 (PDK4) plays a pivotal role in the regulation of cellular proliferation and apoptosis. The objective of this study was to examine whether the genetic depletion of the PDK4 gene attenuates hyperoxia-induced lung injury in neonatal mice.

Methods: Neonatal PDK4-/- mice and wild-type (WT) mice were exposed to oxygen concentrations of 21% (normoxia) and 95% (hyperoxia) for the first 4 days of life.

Prognosis of pediatric ulcerative colitis after infliximab failure: A multicenter registry-based cohort study.

Background And Aim: Even with increasing numbers of biologic agents available for management of ulcerative colitis (UC), infliximab (IFX) retains an important place in treatment of pediatric patients with this disease. As few reports have addressed outcomes in pediatric UC patients who had to discontinue IFX, we examined clinical course and prognosis after IFX failure in pediatric UC.

Methods: A prospective cohort study of pertinent cases enrolled in the Japanese Pediatric Inflammatory Bowel Disease Registry between 2012 and 2020 was conducted to determine outcomes for pediatric UC patients who received IFX but required its discontinuation during follow-up (IFX failure).

Identification of small-sized intrachromosomal segments at the ends of INV-DUP-DEL patterns.

The mechanism of chromosomal rearrangement associated with inverted-duplication-deletion (INV-DUP-DEL) pattern formation has been investigated by many researchers, and several possible mechanisms have been proposed. Currently, fold-back and subsequent dicentric chromosome formation has been established as non-recurrent INV-DUP-DEL pattern formation mechanisms. In the present study, we analyzed the breakpoint junctions of INV-DUP-DEL patterns in five patients using long-read whole-genome sequencing and detected 2.

Clinical outcome of ulcerative colitis with severe onset in children: a multicenter prospective cohort study.

Background: As best practices for treating children with severe-onset ulcerative colitis remain controversial in the era of biologic agents, we prospectively investigated treatments and outcomes in a multicenter cohort.

Methods: Using a Web-based data registry maintained in Japan between October 2012 and March 2020, we compared management and treatment outcomes in an S1 group defined by a Pediatric Ulcerative Colitis Activity Index of 65 or more points at diagnosis with those in an S0 group defined by an index value below 65.

Results: Three hundred one children with ulcerative colitis treated at 21 institutions were included, with follow-up for 3.

Rare diseases presenting with hemophagocytic lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal hyperinflammatory disorder characterized by hypercytokinemia caused by excessive activation of cytotoxic T cells and macrophages. HLH is caused by a variety of factors and is classified into primary and secondary HLH. Familial HLH (FHL) types 1-5, X-linked lymphoproliferative syndrome types 1 and 2, and FHL syndrome with hypopigmentation are all examples of primary HLH.

A Survey of Genetic Counseling for Non-invasive Prenatal Testing Examinees in Akita.

Introduction: In recent years, there has been an increase in noninvasive prenatal testing (NIPT), where maternal blood samples are used to extract fetal cell-free DNA. Despite this being offered in several facilities in urban areas, NIPT remains to be scarcely unavailable in rural areas. Moreover, there is lacking information with regard to how pregnant women in rural areas perceive NIPT.

Diagnosis of SLC25A46-related pontocerebellar hypoplasia in two siblings with fulminant neonatal course: role of postmortem CT and whole genomic analysis: a case report.

Background: Pontocerebellar hypoplasia (PCH) is increasingly known as a degenerative disease rather than simple "hypoplasia". At least 21 disease-causing genes have been identified for PCH so far. Because PCH is very heterogenous, prognostic prediction based solely on clinical or radiologic findings is not feasible.

E44Q mutation in Na1.7 in a patient with infantile paroxysmal knee pain: electrophysiological analysis of voltage-dependent sodium current.

Gain-of-function mutations in voltage-gated sodium channels (Na1.7, Na1.8, and Na1.

A Japanese Patient with Genitopatellar Syndrome Transiently Presenting with Cardiac Intramural Cavity during the Neonatal Period.

Genitopatellar syndrome (GPS) is a rare autosomal dominant disorder caused by de novo pathogenic variants in the gene. It is characterized by genital abnormalities, patellar hypoplasia/agenesis, flexion contractures of the hips and knees, corpus callosum agenesis with microcephaly, and hydronephrosis and/or multiple renal cysts. More than half of patients with GPS have congenital heart defects, mostly atrial and/or ventricular septal defects, patent foramen ovale, and patent ductus arteriosus.

Phenotypic characteristics of pediatric inflammatory bowel disease in Japan: results from a multicenter registry.

Background/aims: There are few published registry studies from Asia on pediatric inflammatory bowel disease (IBD). Registry network data enable comparisons among ethnic groups. This study examined the characteristics of IBD in Japanese children and compared them with those in European children.

Development of a Diagnostic Screening Strategy for Niemann-Pick Diseases Based on Simultaneous Liquid Chromatography-Tandem Mass Spectrometry Analyses of N-Palmitoyl-O-phosphocholine-serine and Sphingosylphosphorylcholine.

Early diagnosis of Niemann-Pick diseases (NPDs) is important for better prognosis of such diseases. N-Palmitoyl-O-phosphocholine-serine (PPCS) is a new NPD biomarker possessing high sensitivity, and with its combination with sphingosylphosphocholine (SPC) it may be possible to distinguish NPD-C from NPD-A/B. In this study, a rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method (method 1) and a validated LC-MS/MS analysis (method 2) of PPCS and SPC were developed, and we have proposed a diagnostic screening strategy for NPDs using a combination of serum PPCS and SPC concentrations.

An Early-Onset Neuronopathic Form of Acid Sphingomyelinase Deficiency: A SMPD1 p.C133Y Mutation in the Saposin Domain of Acid Sphingomyelinase.

Acid sphingomyelinase (ASM) is a lysosomal hydrolase that degrades sphingomyelin into ceramide and phosphocholine. Recent crystallographic studies revealed the functional role of the N-terminal ASM saposin domain. ASM deficiency due to mutations in the ASM-encoding sphingomyelin phosphodiesterase 1 (SMPD1) gene causes an autosomal recessive sphingolipid-storage disorder, known as Niemann-Pick disease Type A (NPA) or Type B (NPB).

Clinical Features, Molecular Genetics, and Long-Term Outcome in Congenital Chloride Diarrhea: A Nationwide Study in Japan.

Objective: To clarify clinical and genetic features of Japanese children with congenital chloride diarrhea (CCD).

Study Design: This was a multi-institutional, retrospective survey of 616 pediatric centers in Japan with identified patients with CCD between 2014 and 2018. Mutations involving SLC26A3 were detected by Sanger sequencing.