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The recent World Health Organization (WHO) guideline aims to provide evidence‐based recommendations on complementary feeding (CF) of healthy term infants and young children 6−23 months living in low‐, middle‐, and high‐income countries, including both breastfed and non‐breastfed children. Like WHO, our organizations aim to promote optimal infant and young child nutrition and health, with a focus on promoting breastfeeding as well as appropriate and timely CF. In this paper, we share our concerns about aspects of the guideline, some of which may have the potential to cause unintended harm in infants and young children and suggest alternative or modified proposals.

Citrin deficiency is an autosomal recessive metabolic liver disease caused by mutations in the SLC25A13gene. The disease typically presents with cholestasis, elevated liver enzymes, hyperammonemia, hypercitrullinemia, and fatty liver in young infants, resulting in a phenotype known as “neonatal intrahepatic cholestasis caused by citrin deficiency” (NICCD). The diagnosis relies on clinical manifestation, biochemical evidence of hypercitrullinemia, and identifying mutations in the SLC25A13gene. Several common mutations have been found in patients of East Asian background. The mainstay treatment is nutritional therapy in early infancy utilizing a lactose‐free and medium‐chain triglyceride formula. This approach leads to the majority of patients recovering liver function by 1 year of age. Some patients may remain asymptomatic or undiagnosed, but a small proportion of cases can progress to cirrhosis and liver failure, necessitating liver transplantation. Recently, advancements in newborn screening methods have improved the age of diagnosis. Early diagnosis and timely management improve patient outcomes. Further studies are needed to elucidate the long‐term follow‐up of NICCD patients into adolescence and adulthood. Citrin deficiency: a metabolic disorder causing neonatal cholestasis and steatosis. Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is an autosomal recessive disorder caused by SLC25A13gene mutations that may recover or progress to liver cirrhosis.SLC25A13gene mutations may have a late‐onset phenotype causing neuropsychiatric symptoms in adulthood. Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is an autosomal recessive disorder caused by SLC25A13gene mutations that may recover or progress to liver cirrhosis. SLC25A13gene mutations may have a late‐onset phenotype causing neuropsychiatric symptoms in adulthood. Citrin deficiency has been described in several countries beyond Asia and should be considered in the differential diagnosis of all infants with cholestasis and growth failure.A genetic diagnosis, which is now widely available, is the most reliable tool to confirm citrin deficiency, given the significant variability in both clinical manifestations and genetic mutations.Early diagnosis and treatment results in improved growth and better patient outcomes. Citrin deficiency has been described in several countries beyond Asia and should be considered in the differential diagnosis of all infants with cholestasis and growth failure. A genetic diagnosis, which is now widely available, is the most reliable tool to confirm citrin deficiency, given the significant variability in both clinical manifestations and genetic mutations. Early diagnosis and treatment results in improved growth and better patient outcomes.

DNA polymerase epsilon (Pol ε), a component of the core replisome, is involved in DNA replication. Although genetic defects of Pol ε have been reported to cause immunodeficiency syndromes, its role in haematopoiesis remains unknown. Here, we identified compound heterozygous variants (p.[Asp1131fs];[Thr1891del]) in POLE, encoding Pol ε catalytic subunit A (POLE1), in siblings with a syndromic form of severe congenital transfusion-dependent anaemia. In contrast to Diamond-Blackfan anaemia, marked reticulocytopenia or marked erythroid hypoplasia was not found. Their bone marrow aspirates during infancy revealed erythroid dysplasia with strongly positive TP53 in immunostaining. Repetitive examinations demonstrated trilineage myelodysplasia within 2 years from birth. They had short stature and facial dysmorphism. HEK293 cell-based expression experiments and analyses of patient-derived induced pluripotent stem cells (iPSCs) disclosed a reduced mRNA level of Asp1131fs-POLE1 and defective nuclear translocation of Thr1891del-POLE1. Analysis of iPSCs showed compensatory mRNA upregulation of the other replisome components and increase of the TP53 protein, both suggesting dysfunction of the replisome. We created Pole-knockout medaka fish and found that heterozygous fishes were viable, but with decreased RBCs. Our observations expand the phenotypic spectrum of the Pol ε defect in humans, additionally providing unique evidence linking Pol ε to haematopoiesis.

Non-esophageal eosinophilic gastrointestinal disorders (non-EoE EGIDs) are chronic inflammatory disorders with massive infiltration of eosinophils into the gastrointestinal tract. Food elimination diets are potentially effective treatments. But the existing dietary therapies have various weak points. We developed a new regimen to compensate for the shortcomings of the elemental diet and 6-food elimination diet. The new regimen consists of an amino-acid-based formula, potatoes, vegetables, fruits and restricted seasonings. We named it the “Rainbow Elimination Diet (ED).” The aims of this study were to evaluate the tolerability and safety of this diet.

X-linked inhibitor of apoptosis protein (XIAP) deficiency is an infrequent inborn error of immunity that is often associated with refractory inflammatory bowel disease (IBD). The natural course of XIAP deficiency is typically associated with poor prognosis, and hematopoietic cell transplantation (HCT) is the only curative treatment.

Haploinsufficiency of A20 (HA20) is caused by loss-of-function TNFAIP3variants. Phenotypic and genetic features of HA20 remain uncertain; therefore, the clinical distinction between HA20 and Behçet’s disease (BD) requires clarification. We have collected 12 Japanese BD-like families. Probands of these families were analyzed by whole exome sequencing (WES) and subsequent Sanger sequencing. Clinical features were compared between 54 HA20 patients (including previously reported and new cases) and 520 Japanese BD patients. We identified c.1434C>A:p.(Cys478*) in one family and a 236 kb deletion at 6q23.3 containing TNFAIP3in another family. Four HA20 patients in the two families presented with childhood-onset recurrent oral and genital ulcers and were initially diagnosed and treated as BD. Consistent with the clinical features of HA20, recurrent, refractory fever attacks (three of four patients), and digestive ulcers (two of the four patients) were observed. A comparison of clinical features between HA20 patients and cohorts of BD patients revealed several critical features specific to HA20. These were early-onset, familial occurrence, recurrent fever attacks, gastrointestinal involvement, and infrequent ocular involvement. We identified a novel nonsense variant and deletion of the entire TNFAIP3gene in two unrelated Japanese HA20 families. Genetic screening of TNFAIP3should be considered for familial BD-like patients with early-onset recurrent fevers.

We encountered a case of Bacillus Calmette-Guérin (BCG) cervical lymphadenitis in a patient undergoing infliximab after 6 years from BCG vaccination. Tumor necrosis factor-α inhibitors may be a risk for reactivation of BCG and serious infection even several years after vaccination.

Non-IgE-mediated gastrointestinal food allergies (non-IgE-GIFAs) seem to be increasing rapidly worldwide. However, nationwide studies have been limited to food-protein-induced enterocolitis (FPIES) and food-protein-induced allergic proctocolitis (FPIAP), with little attention to other non-IgE-GIFA subgroups. The aim of this study was to elucidate the clinical features of all patients with non-IgE-GIFAs, not just certain subgroups.

Chronic granulomatous disease (CGD) is a rare inherited disorder in which phagocytes are unable to eradicate pathogens because of a deficit of nicotinamide adenine dinucleotide phosphate oxidase. Among CGD patients, ~30% to 50% develop severe gastrointestinal tract symptoms. Although characteristic histologic findings of CGD-associated colitis have been reported, information on endoscopic features remained vague. A total of 8 male patients with CGD (ages 2–23 years) from 2 Japanese institutions underwent colonoscopy for the evaluation of their fever, diarrhea, bloody stool, and abdominal pain. The endoscopic and histologic findings were retrospectively reviewed. The endoscopic findings of CGD-associated colitis appeared varied. Notably, brownish dots over a yellowish edematous mucosa were observed in 3 of the 8 patients. Prominent pigment-laden macrophages were noted histologically on the mucosa. Although nonspecific endoscopic findings of CGD-associated colitis have been reported before, our observation of brownish dots spread across a yellowish edematous mucosa, termed “leopard sign,” could be a unique feature of this condition.

We report a rare case of hepatocellular carcinoma in native liver in a case of biliary atresia. The patient was a 38-year-old female with three children who had an aggressive tumor, resulting in her subsequent death. We also review 14 reports, published previously in the English language medical literature, concerning hepatocellular carcinoma originating from native liver in biliary atresia cases and discuss the possible etiology, and propose more careful follow up for the patients with biliary atresia who suffer from repetitive cholangitis and/or experience the child delivery.

Aberrant right subclavian artery (ARSA)-esophageal fistula has rarely been reported but has fatal outcomes in most cases. We report a 10-year-old girl who presented with massive hematemesis during recovery from a head injury caused by a motor vehicle accident. Prompt detection of the esophageal bleeding point by esophagoscopy followed by a balloon tamponade led to temporary hemostasis, during which time an emergency operation was prepared and started promptly. Two-staged surgery was performed with a successful outcome; direct vascular access to the right atrium and suturing of the bleeding point of ARSA through a T-shaped skin incision with median sternotomy were performed in the first surgery, and dividing the ARSA and repairing the esophagus were performed in the second surgery on the following day. Multidisciplinary treatment with pediatric intensivists, gastroenterologists, cardiovascular surgeons, and general surgeons is essential to address the near-fatal complication of ARSA in children.

Although macrophage activation syndrome (MAS) develops in some patients with chronic granulomatous disease (CGD), all of the reported cases have been associated with pathogenic microbial infections. We report a 2-year-old boy with CGD-associated colitis who suffered from MAS without any clinical signs of a microbial infection. He was treated with 1 course of methylprednisolone pulse therapy and the clinical symptoms improved; however, the colitis was difficult to control even with immunosuppressive drugs, and he eventually required hematopoietic stem cell transplantation 1 year after the onset of MAS. It is likely that MAS develops in patients with CGD colitis independent of microbial infections.

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Radical copolymerizability of 6-methyl-2-vinyl-3-pyridazinone (I) has been reinvestigated in acetic acid and also in the presence of polyacrylic acid (PAA). Copolymerization of styrene with I was carried out in a few solvents. A positive e2 value was obtained in acetic acid while negative ez values were obtained in benzene and DMF. I was allowed to copolymerize with a few monomers such as styrene, methyl methacrylate, and acrolein in the presence of PAA to give block-type copolymers. All these observations indicate that polymerizability of I is controlled by the hydrogen bonding interaction between the carbonyl group of I and the hydroxyl group of the additive.

Groove pancreatitis is a type of pancreatitis where inflammation occurs in the “groove area” which is the narrow space surrounded by the duodenum, head of the pancreas and common bile duct, where lymph nodes, blood vessels and pancreatic duct exist. Groove area inflammation causes duodenal stenosis/obstruction, narrowing of the extrahepatic biliary tree and sometimes pancreatitis. The exact etiology of the disease is not well understood but Santorini duct obstruction (congenital or acquired) may be associated with inflammation of the groove area, which is partly caused by excessive alcoholic intake or gastric/duodenal peptic ulcer in adults.

Eosinophilic gastritis (EG) is clinicopathologically characterized by both marked gastric eosinophilia and clinical symptoms. The endoscopic findings in EG vary among patients, leading to clinical confusion. However, little is known about the relationship between precise endoscopic findings and the pathophysiological process responsible for EG.