Sonoko Kondo

Glycogen storage disease type IV (Andersen disease) is caused by a deficiency of the glycogen branching enzyme. We report a case in which liver biopsy played a key role in establishing the diagnosis. A 2-year-old girl presented to our hospital with hepatomegaly. Despite extensive testing, no definitive diagnosis was made, prompting a liver biopsy. The biopsy tissue revealed characteristic cytoplasmic inclusions. Genetic analysis identified a mutation in the GBE1 gene, confirming the diagnosis of glycogen storage disease type IV. Various special stains were helpful in characterizing the accumulated substances.

Inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn’s disease, are chronic disorders relating to gut microbiota dysbiosis. Despite severe pancolitis being more prevalent in pediatric UC than in adults, alterations in the colon mucosa-associated microbiota (MAM) and their association with disease severity remain to be elucidated. The present study aimed to compare the gut microbiota in colon lavage fluids (CLFs) and fecal samples from 19 pediatric UC and 19 non-IBD patients. The community structure of MAM inferred by 16S metagenomic analysis was similar throughout the colon regardless of disease type. Bacterial compositions between MAM and feces were significantly different in non-IBD, while no difference was observed in pediatric UC, indicating a compromised mucous layer that could not sufficiently separate the MAM and luminal microbiota in UC. In pediatric UC, homogenous distribution of MAM was gradually disordered with increases in disease activity or mucosal inflammation, and bacterial groups of upper digestive tract or environmental origin were more abundant in MAM. Monitoring key bacterial markers in MAM, which include Lactobacillus and Enterococcus or Faecalibacterium and Blautia as increased or reduced members in pediatric UC, respectively, might be useful for evaluation of patient prognosis.

Heterozygous familial hypercholesterolemia (HeFH) strongly predisposes individuals to atherosclerosis, including coronary artery disease, leading to death from cardiovascular diseases in > 60% of untreated cases. Appropriate intervention from childhood is necessary. In Japan, only pitavastatin is approved for pediatric FH. A poor response to statins makes treatment challenging; optimal intervention may require combination therapy.

Background: Achilles tendon (AT) thickening reflects cumulative low-density lipoprotein cholesterol (LDL-C) exposure. The Japan Atherosclerosis Society (JAS) explicitly includes AT thickness as a diagnostic criterion for familial hypercholesterolemia (FH) in adults, whereas internationally, it is not a standard diagnostic measure. However, the clinical significance of AT thickening in pediatric populations remains unclear. Methods: We conducted a single-center, retrospective, observational study involving pediatric patients (11–18 years old) with suspected FH through standardized universal lipid screening across Kagawa Prefecture, Japan. Genetic testing confirmed FH through pathogenic variants in the LDLR, PCSK9, or APOB genes. The AT thickness was measured using a standardized ultrasonography protocol. We assessed associations between the FH status, cumulative LDL-C levels, and AT thickness. Results: In the pediatric patients, no significant difference in the AT thickness was observed between the FH and non-FH groups (median 4.4 vs. 4.5 mm; p = 0.570). Cumulative LDL-C was higher in the FH group, while no clear association between cumulative LDL-C and AT thickness was apparent in either group. Conclusions: In this single-center, retrospective study of pediatric patients identified through standardized universal lipid screening, no significant differences were found in AT thickness between FH and non-FH groups although cumulative LDL-C levels were higher in the FH group. Given methodological limitations (small sample size, selection bias, and residual confounding related to statin therapy and growth), these findings should be interpreted as exploratory rather than confirmatory. Regardless of genotype, early risk management may be warranted.

Ulcerative colitis (UC) is caused by an excessive immune response to gut microbiota. A recent study reported that the population of IgG-coated gut microbes increases with disease severity in patients with UC, but the role of these IgG-coated microbes in UC pathology is unclear. Serum, feces and colonoscopic lavage fluids (CLFs) were collected from pediatric UC (n = 13) and non-inflammatory bowel disease (IBD) patients (n = 15). Gut microbes were isolated from feces. Serum IgG reactivity to microbial cells and CLF-derived proteins was evaluated by Western blotting. Complement activation by the bacteria–IgG complexes was also assessed. Serum IgG reactivity to gut microbial extracts was highly variable in patients with active UC and increased with mucosal inflammation. IgG reactivity and clinical condition were inversely associated depending on disease activity. Non-IBD patients showed a similar degree of serum IgG response as that seen for patients whose UC was in remission. Lactobacillaceae bound higher amounts of IgG than other gut microbes tested and absorbed IgG to other bacteria. Lacticaseibacillus paracasei suppressed complement activation by Escherichia coli—IgG immune complexes. Appropriate IgG responses to luminal microbes might play a key role in gut microbiota stability by reducing excessive mucosal inflammation.

BACKGROUND Heterozygous familial hypobetalipoproteinemia (FHBL) is a semi-autosomal disorder that is caused mainly by an APOB variant. It is usually asymptomatic and rarely leads to non-alcoholic steatohepatitis (NASH). CASE SUMMARY A 12-year-old boy was referred to our hospital after prolonged elevation of liver enzymes was observed during health checkups in Kagawa Prefecture. Abdominal ultrasound showed a bright liver, and laboratory investigations revealed low low-density lipoprotein cholesterol and apolipoprotein B protein levels. His family history included fatty liver and hypolipidemia in his father, which led to a clinical diagnosis of FHBL. A liver biopsy was performed on suspicion of liver fibrosis based on biomarkers. The liver tissue showed fatty steatosis, inflammation, hepatocyte ballooning, and fibrosis, indicating NASH. Genetic testing detected the APOB variant, and the patient was treated successfully with vitamin E. CONCLUSION It is important to assess family history and liver dysfunction severity in non-obese patients with hypolipidemia and fatty liver.