Osteogenesis imperfecta (OI) is a congenital skeletal disorder characterized by varying degrees of bone fragility and deformities. Extraskeletal manifestations, such as blue sclera, dentinogenesis imperfecta, growth disturbance, hearing impairment, and muscle weakness, occasionally accompany OI. Many genes have been identified as causative of OI, such as the type I collagen gene and genes involved in the folding, processing, and crosslinking of type I collagen molecules, osteoblast differentiation, and bone mineralization. According to the discovery of the causative gene of OI, nosology and classifications have also been revised and the “dyadic approach” based nomenclature according to the severity and each causative gene of OI was recently adopted. Intravenous or oral bisphosphonates have been administered to treat bone fragility in children with OI and a reduction in the frequency of bone fractures has been reported. However, despite the increase of bone mineral density, evidence of bone fracture prevention is limited. Recently, excessive transforming growth factor β signaling pathway and excessive endoplasmic reticulum stress have been reported as the pathogenesis of OI, and treatment strategies based on these pathogeneses have been developed. This review summarizes the molecular basis, transition of nosology and classification, status of bisphosphonate therapy, and development of treatment strategies.

Advanced glycation end-products (AGEs) formed by non-enzymatic glycation reactions between sugars and proteins have been implicated in various age-related disorders. Skin autofluorescence (SAF) is a noninvasive method for estimating the accumulated AGEs levels in the human body. However, the SAF values in healthy children have not yet been reported. This study aimed to determine reference values and factors affecting SAF values in apparently healthy schoolchildren. The study included 426 children (aged 8.9 ± 1.7 yr), including 224 boys and 202 girls from one public elementary school. SAF values were measured using an AGE reader. Data on the perinatal history, eating and exercise habits, lifestyle, family background, and medical history of the participants and their family medical history were collected using a questionnaire. The mean SAF value of the participants was 1.06 ± 0.19 AU, lower than that of healthy adults, and did not increase with calendar age. Moreover, a family history of diabetes within second-degree relatives was the sole significant factor associated with SAF values (p = 0.045), and it exhibited no association with life environmental factors. In conclusion, genetically defined susceptibility to glycation may be the most important factor in AGE accumulation in schoolchildren.

Rapid genetic diagnosis of differences/disorders of sex development (DSD) through minimally invasive testing is desirable. In this study, we performed PCR amplicon-based next-generation sequencing (NGS) targeting AR and SRD5A2 using dried blood spots from 22 patients with 46,XY DSD. We compared the results with those of an outsourced capture-based NGS using venous blood-derived DNA. We successfully extracted DNA from the dried blood spots and obtained analysis results for 19 of the 22 cases within a minimum of seven days. The DNA quantity required was significantly lower for amplicon-based NGS using dried blood spots than for capture-based NGS using venous blood (median 8.7 ng vs. 1434.8 ng). We identified four single-nucleotide substitutions in SRD5A2 in 16 of the 19 cases. The results were consistent between the two NGS analyses and Sanger sequencing using venous blood, except for case 1. In this case, amplicon-based NGS using dried blood spots incorrectly identified a heterozygous SRD5A2 variant as homozygous, presumably due to allelic dropout. In conclusion, we demonstrated that amplicon-based NGS using dried blood spots allowed for rapid and minimally invasive genetic testing in patients with 46,XY DSD. However, optimizing DNA extraction from dried blood spots and validating detected variants using Sanger sequencing are necessary.

Globally, the incidence of precocious puberty increases with a decline in age of pubertal onset. Simultaneously, the rate of hospital referrals for children in early puberty has increased. This study is the first survey of Japanese parents of children who visited a hospital for referral about early puberty to clarify their parents’ concerns. We conducted a survey using an initial medical questionnaire between April 2019 and May 2023. In total, 230 parents completed the questionnaire during their first visit. Over half of the parents were concerned about puberty and desired aggressive treatment. The most common concerns were children’s height prognosis and early menarche in girls. Psychological problems were relatively infrequent. Only 20% of children had indications for treatment. Our survey showed that many children were referred to our department preceded by their parents’ excessive anxiety and quest for treatment. Psychological issues may not be a major determinant of an indication for therapy with central precocious puberty. Providing sufficient explanations and correct information on puberty is important to alleviate parental anxiety and reduce unnecessary referrals.

Congenital hyperinsulinism (CHI) is characterized by hypoglycemia caused by excessive insulin secretion. CHI is classified into two types: transient CHI, which resolves within 3–4 mo of birth, and persistent CHI, which persists beyond this period. Diazoxide, the first-line treatment for CHI, may cause pulmonary hypertension (PH) as a side effect. Here, we report the case of a 2-mo-old girl with CHI and an atrial septal defect who initially responded well to diazoxide but developed dose-dependent PH. Diazoxide was discontinued, and treatment was switched to octreotide, glycogen storage disease milk, and glucagon. However, maintaining stable blood glucose levels remained challenging. Surgical intervention is typically required when medical management is ineffective; however, such procedures are limited to specialized facilities. Additionally, pancreatic resection carries a high risk of postoperative diabetes. To enable the safe reintroduction of diazoxide, we surgically closed the atrial septal defect with a left-to-right shunt and combined diazoxide therapy with anti-PH medication. This approach successfully controlled PH and achieved good glycemic control.

Latent autoimmune diabetes in the young (LADY), also known as slowly progressive insulin-dependent diabetes mellitus (SPIDDM), is a slowly progressive form of type 1 diabetes (T1D) characterized by positive islet-related autoantibodies and, typically, an initial type 2 diabetes (T2D) phenotype. Although approximately 10% of children with T2D have positive islet-related autoantibodies, reports on the clinical course of patients with LADY are limited. We present the case of a 17-yr-old female initially diagnosed with T2D based on a body mass index (BMI) of 27 kg/m², obesity, and preserved endogenous insulin secretion. Notably, the glutamic acid decarboxylase antibody (GADA) test results fluctuated between weakly positive and negative. She developed diabetic ketosis 9 mo later, with a weak GADA titer and a high zinc transporter-8 antibody (Zn-T8A) titer, confirming autoimmune β-cell destruction consistent with T1D. Subsequent human leukocyte antigen (HLA) testing revealed the presence of the DRB1*15:02-DQB1*06:01 haplotype, which is considered protective against T1D. This case report details the clinical course of LADY, emphasizes close follow-up and re-evaluation of multiple islet-related autoantibodies in patients to distinguish LADY from T2D, and suggests that a protective HLA haplotype may have contributed to the slow onset despite high-titer Zn-T8A.