Okayama University Medical SchoolActa Medica Okayama0386-300X8022026Revisiting Adrenal Crisis Triggered by Influenza Infection: Lessons from Two Fatal Cases153157ENYoshiyukiUedaDepartment of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTetsuyaYumotoDepartment of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakashiHongoDepartment of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakafumiObaraDepartment of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTsuyoshiNojimaDepartment of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKoheiTsukaharaDepartment of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKoseiHasegawaDepartment of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNatsukoFutagawaDepartment of Pediatrics, Okayama University HospitalHiromichiNaitoDepartment of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityAtsunoriNakaoDepartment of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityCase Report10.18926/AMO/70458Adrenal crisis is a life-threatening endocrine emergency that can progress within hours despite a prior diagnosis and maintenance therapy. We describe a fatal influenza-triggered adrenal crisis in two patients: a child with panhypopituitarism and an adult with prior pituitary surgery, both presenting in cardiac arrest. Despite resuscitation and intravenous hydrocortisone, a fatal hypoxic-ischemic injury or multiorgan failure occurred. These cases highlight the fulminant course of an adrenal crisis and underscore the importance of early recognition, clinician awareness, prompt parenteral hydrocortisone administration, and reinforcement of education for patients, caregivers, and healthcare providers to improve preparedness and prevent avoidable deaths.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama2950-2217322025Erythromelalgia presenting with posterior reversible encephalopathy syndrome: A pediatric case report100078ENKengoSuzukiDepartment of Pediatrics, Okayama University HospitalKazuhiroUdaDepartment of Pediatrics, Okayama University HospitalMitsuruTsugeDepartment of Pediatric Acute Diseases, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKyosukeArakawaDepartment of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenjiShigeharaDepartment of Pediatrics, Okayama University HospitalTakafumiObaraDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKoseiHasegawaDepartment of Pediatrics, Okayama University HospitalHirokazuTsukaharaDepartment of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground: Erythromelalgia is a rare disorder characterized by erythema, warmth, and burning pain in the extremities. We report a pediatric case of erythromelalgia in a patient who developed posterior reversible encephalopathy syndrome (PRES), without any cutaneous signs.<br>
Case presentation: A previously healthy 12-year-old girl presented to our pediatric clinic with burning extremity pain that had persisted for 6 weeks. The patient was treated with analgesics; however, the pain was refractory to these agents. Seven days after the first visit, she developed afebrile seizures and was transferred to our hospital. Her initial blood pressure was 139/105 mmHg (+2.0 SD), and brain magnetic resonance imaging revealed high intensity areas in the bilateral parietal and occipital lobes, leading to a diagnosis of PRES. Her blood pressure was difficult to control with anti-hypertensive agents. Burning pain in her extremities was relieved by cooling and worsened by warming. Although erythema was not observed in her hands or legs, erythromelalgia was suspected based on the characteristic nature of her pain. Intravenous lidocaine was administered for diagnosis, which was dramatically effective. After initiating mexiletine, the burning pain in her extremities disappeared, and hypertension improved. A final diagnosis of erythromelalgia with PRES was made.<br>
Conclusion: A history of temperature-dependent pain relief and deterioration are important indicators of disease diagnosis, even if patients indicate a lack of erythema or warmth. Physicians should be aware that persistent pain due to erythromelalgia can lead to refractory hypertension and development of PRES.No potential conflict of interest relevant to this article was reported.Japanese Society for Pediatric EndocrinologyActa Medica Okayama0918-57393432025Osteogenesis imperfecta: pathogenesis, classification, and treatment152161ENKoseiHasegawaDepartment of Pediatrics, Okayama University HospitalOsteogenesis 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 gdyadic approachh 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 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.No potential conflict of interest relevant to this article was reported.Japanese Society for Pediatric EndocrinologyActa Medica Okayama0918-57393422025Effect of calcium supplementation on bone deformity and histopathological findings of skin papules in a pediatric patient with vitamin D–dependent rickets type 2A: A case report131136ENKoseiHasegawaDepartment of Pediatrics, Okayama University HospitalTomokoMiyakeDepartment of Dermatology, Okayama University HospitalMinaKobashiDepartment of Dermatology, Okayama University HospitalTomonoriTetsunagaDepartment of Dermatology, Okayama University HospitalYukoAgoDepartment of Pediatrics, Okayama University HospitalNatsukoFutagawaDepartment of Pediatrics, Okayama University HospitalHiroyukiMiyaharaDepartment of Pediatrics, Okayama University HospitalYousukeHiguchiDepartment of Pediatrics, Okayama University HospitalShinMorizaneDepartment of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHirokazuTsukaharaDepartment of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesVitamin D–dependent rickets type 2A (VDDR2A) is an autosomal recessive disease caused by pathogenic variants of the vitamin D receptor (VDR) gene. VDDR2A rickets are usually resistant to native or active vitamin D treatment because of impaired active calcium absorption against the calcium concentration gradient, which is a ligand-dependent VDR action in the small intestine. Alopecia due to an impaired skin follicular cycle is occasionally observed in patients with VDDR2A. Among the pathogenic VDR variants, most in the DNA-binding domain and some in the ligand-binding domain, which affect the dimerization of VDR with the retinoic X receptor, are associated with alopecia. Herein, we report a case of VDDR2A caused by compound heterozygous pathogenic variants of the DNA-binding domain of VDR. Active vitamin D treatment did not ameliorate genu varum, rachitic changes in the roentgenogram, or abnormal laboratory findings. However, oral administration of calcium lactate dramatically improved these findings. The patient also experienced hair loss at two months of age and multiple papules on the skin at two yr of age, which did not improve with vitamin D or calcium supplementation. We also report the histopathological findings of skin papules in this patient.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama1661-65962662025Involvement of a Novel Variant of FGFR1 Detected in an Adult Patient with Kallmann Syndrome in Regulation of Gonadal Steroidogenesis2713ENYoshiakiSoejimaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukiOtsukaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMarinaKawaguchiDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKoheiOguniDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKoichiroYamamotoDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasuhiroNakanoDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMihoYasudaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazukiTokumasuDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKeigoUedaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKoseiHasegawaDepartment of Pediatrics, Okayama University HospitalNahokoIwataDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesFumioOtsukaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesFibroblast growth factor receptor 1 (FGFR1), also known as KAL2, is a tyrosine kinase receptor, and variants of FGFR1 have been detected in patients with Kallmann syndrome (KS), which is a congenital developmental disorder characterized by central hypogonadism and anosmia. Herein, we report an adult case of KS with a novel variant of FGFR1. A middle-aged male was referred for a compression fracture of a lumbar vertebra. It was shown that he had severe osteoporosis, anosmia, gynecomastia, and a past history of operations for cryptorchidism. Endocrine workup using pituitary and gonadal stimulation tests revealed the presence of both primary and central hypogonadism. Genetic testing revealed a novel variant of FGFR1 (c.2197_2199dup, p.Met733dup). To identify the pathogenicity of the novel variant and the clinical significance for the gonads, we investigated the effects of the FGFR1 variant on the downstream signaling of FGFR1 and gonadal steroidogenesis by using human steroidogenic granulosa cells. It was revealed that the transfection of the variant gene significantly impaired FGFR1 signaling, detected through the downregulation of SPRY2, compared with that of the case of the forced expression of wild-type FGFR1, and that the existence of the variant gene apparently altered the expression of key steroidogenic factors, including StAR and aromatase, in the gonad. The results suggested that the novel variant of FGFR1 detected in the patient with KS was linked to the impairment of FGFR1 signaling, as well as the alteration of gonadal steroidogenesis, leading to the pathogenesis of latent primary hypogonadism.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0167-594X17222025Identification of factors related to functional prognoses in craniopharyngiomas471479ENTsuyoshiUmedaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshihiroOtaniDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKentaroFujiiDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJojiIshidaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShuichiroHiranoDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasukiSurugaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNaoyaKemmotsuDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyojiImotoDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasuhitoKegoyaRyoMizutaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoheiInoueDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMadokaHokamaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSeiichiroMakiharaDepartment of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKoseiHasegawaDepartment of Pediatrics, Okayama University HospitalKenichiInagakiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesFumioOtsukaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakaoYasuharaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShotaTanakaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesPurpose Craniopharyngiomas are histologically benign tumors, but their proximity to vital neurovascular structures can significantly deteriorate functional prognoses and severely restrict patientsf social interaction and activity. We retrospectively identified risk factors related to the functional prognoses in patients with craniopharyngioma treated at our center.<br>
Methods A retrospective analysis was conducted on 40 patients who underwent surgery for craniopharyngioma and follow-up at our institution between 2003 and 2022. Functional prognoses were evaluated in terms of obesity (body mass index [BMI] ≥ 25 for adults, BMI-Z ≥ 1.65 for children), visual function, endocrine function, and social participation. We investigated whether patient characteristics, tumor size, tumor location, hypothalamic involvement, surgical hypothalamic damage, extent of resection, and recurrence rate correlated with these functional prognostic factors.<br>
Results The median age at diagnosis was 28.0 years, with a median follow-up of 80.5 months. Postoperative obesity was present in 22 patients, and those with postoperative obesity had a significantly higher preoperative BMI or BMI-Z (preoperative BMI for adults: p = 0.074; preoperative BMI-Z for children: p = 0.020) and were significantly correlated with preoperative hypothalamic involvement grade 2 (p = 0.012) and surgical hypothalamic damage grade II (p = 0.0001). Deterioration in social participation was significantly associated with a larger tumor size (p = 0.023) and tumor recurrence (p = 0.0047).<br>
Conclusions Patients with higher preoperative BMI or BMI-Z and hypothalamic involvement have a greater risk of postoperative obesity, and larger tumor size and recurrence can significantly deteriorate the rate of patientsf social participation.No potential conflict of interest relevant to this article was reported.Frontiers MediaActa Medica Okayama2296-2360122024Trabecular bone scores in children with osteogenesis imperfecta respond differently to bisphosphonate treatment depending on disease severity1500023ENNatsukoFutagawaDepartment of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKoseiHasegawaDepartment of Pediatrics, Okayama University HospitalHiroyukiMiyaharaDepartment of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroyukiTanakaDepartment of Pediatrics, Okayama Saiseikai General HospitalHirokazuTsukaharaDepartment of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesIntroduction: Osteogenesis imperfecta (OI) is a congenital skeletal disorder characterized by bone fragility. Bisphosphonates (BISs) have become the mainstream treatment in children with OI. However, an optimal treatment protocol has not yet been established, while BIS treatment tends to be administered to normalize bone mineral density (BMD). Bone quality is an important component of bone strength. The trabecular bone score (TBS) is a quantitative measure of the microstructure that affects bone quality. This study investigated the TBS during BIS treatment in children with OI. Materials and methods: Twenty-nine children with OI were enrolled and classified into two groups: mild (type 1) and moderate to severe (types 3 and 4). Dual-energy x-ray absorptiometry images were retrospectively analyzed for TBS calculation. The relationship between the areal BMD (aBMD), its Z-score, height-adjusted BMD (BMDHAZ) Z-score, TBS, and TBS Z-score with the treatment duration was assessed for each group. Results: In the mild group, the aBMD, its Z-score, and BMDHAZ Z-score showed a significant positive correlation with treatment duration (r = 0.68, 0.68, 0.72, respectively, p < 0.01). The TBS Z-score tended to increase with treatment duration, albeit without reaching significance. In the moderate to severe group, the TBS Z-score showed a significant positive correlation with treatment duration (r = 0.48, p < 0.01), in contrast to the aBMD Z-score, which did not increase. Finally, the BMDHAZ Z-score only showed a weak positive correlation with treatment duration (r = 0.37, p < 0.01). Conclusion: Because BIS affect the BMD and TBS differently based on the severity of OI, treatment goals may need to be stratified by disease severity.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1758-81031422023Trends in childhood obesity in Japan: A nationwide observational study from 2012 to 2021e12636ENShintaroFujiwaraDepartment of Pediatrics, NHO Okayama Medical CenterKoHaradaDepartment of Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai Beth IsraelHideharuHagiyaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshihiroKoyamaDepartment of Pharmaceutical Biomedicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKoseiHasegawaDepartment of Pediatrics, Okayama University HospitalHirokazuTsukaharaDepartment of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesFumioOtsukaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesThe persistent ascension of childhood obesity on a global scale constitutes a significant quandary. The prevalence of childhood obesity in Japan peaked in the early 2000s and has been reported to have declined since then, but recent data and its trend including the novel coronavirus disease 2019 (COVID-19) pandemic era are not available. Moreover, there is a dearth of studies examining the correlation between the trend in childhood obesity and exercise habits over the past decade. This study aims to examine the changes in the prevalence of obesity, physical fitness, and exercise habits over the past 10 years in Japanese children. We investigated the prevalence of childhood obesity in Japan, using the School Health Statistics Survey data from 2012 to 2021. The dataset has a sample size representative of children nationwide and includes variables for obesity, such as height, weight, and age. Data were classified into groups by sex and age (6–8, 9–11, and 12–14 years age). Children weighing 20% or more of the standard body weight are classified as obese. The annual percentage changes and average annual percentage changes were estimated using the joinpoint regression model. We also examined the trends in the physical fitness test score and exercise time. Average annual percentage changes of boys increased, especially in the 6- to 8-year age group (3.4%–4.6%). For girls, average annual percentage changes had increased in 6- to 8-year (2.5%–4.0%) and 9- to 11-year (0.9%–2.2%) age groups. Since the late 2010s, significantly increasing annual percentage changes were observed in 12- to 14-year age boys (6.7%–8.9%) and girls of many age groups (2.6%–8.6%). The physical fitness test score and exercise time showed decreasing trends since the late 2010s. Childhood obesity may have generally risen in Japan, in the last decade. Encouraging healthy eating and physical activity through school policies and curricula is necessary.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1552-482519452023Radiological characteristics of skeletal growth in neonates and infants with achondroplasiae63525ENDaisukeMiyaharaDepartment of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKoseiHasegawaDepartment of Pediatrics, Okayama University HospitalYukoAgoDepartment of Pediatrics, Okayama University HospitalNatsukoFutagawaDepartment of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroyukiMiyaharaDepartment of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYousukeHiguchiDepartment of Pediatrics, Okayama University HospitalKazukiYamadaDepartment of Orthopedics, Okayama University HospitalTomonoriTetsunagaDepartment of Orthopedics, Okayama University HospitalTadashiMoriwakeDepartment of Pediatrics, Iwakuni Clinical Center, National Hospital OrganizationHiroyukiTanakaDepartment of Pediatrics, Okayama Saiseikai General HospitalHirokazuTsukaharaDepartment of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAchondroplasia (ACH) is the most common form of skeletal dysplasia characterized by a rhizomelic short stature. Radiological skeletal findings in pediatric and adult patients with ACH include short long bones, a relatively longer fibula compared to the tibia, a narrow lumbar interpedicular distance, and a hypoplastic iliac wing. Nonetheless, the characteristics of skeletal growth during the neonatal and infantile periods have scarcely been explored. Therefore, this retrospective study aimed to analyze the radiological skeletal growth during the neonatal and infantile periods in 41 Japanese patients with genetically confirmed ACH. The length of long bones in the upper and lower limbs and the lumbar interpedicular distances at L1 and L4 were measured. These parameters showed significant positive correlations with age. The upper segment-to-lower segment ratio in the lower limbs resembled the data of healthy controls from previous reports. The L1/L4 and fibula/tibia ratios increased with age, suggesting that some representative skeletal phenotypes of ACH were less distinct during the neonatal and infantile periods. In conclusion, for the first time, this study radiologically characterized skeletal growth during the neonatal and infantile periods of patients with genetically confirmed ACH.No potential conflict of interest relevant to this article was reported.Japanese Society for Pediatric EndocrinologyActa Medica Okayama0918-57393242023Novel and recurrent COMP gene variants in five Japanese patients with pseudoachondroplasia: skeletal changes from the neonatal to infantile periods221227ENKoseiHasegawaDepartment of Pediatrics, Okayama University HospitalNatsukoFutagawaDepartment of Pediatrics, Okayama University HospitalYukoAgoDepartment of Pediatrics, Okayama University HospitalHiroyukiMiyaharaDepartment of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesDaisukeHaradaDepartment of Pediatrics, JCHO Osaka HospitalMariMiyazawaDepartment of Pediatrics, Kochi Health Sciences CenterJunkoYoshimotoDepartment of Pediatrics, Okayama University HospitalKenjiBabaDepartment of Pediatrics, Okayama University HospitalTadashiMoriwakeDepartment of Pediatrics, Iwakuni Clinical Center, National Hospital OrganizationHiroyukiTanakaDepartment of Pediatrics, Okayama Saiseikai General HospitalHirokazuTsukaharaDepartment of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesPseudoachondroplasia (PSACH) is an autosomal dominant skeletal dysplasia caused by pathogenic variants of cartilage oligomeric matrix protein (COMP). Clinical symptoms of PSACH are characterized by growth disturbances after the first year of life. These disturbances lead to severe short stature with short limbs, brachydactyly, scoliosis, joint laxity, joint pain since childhood, and a normal face. Epimetaphyseal dysplasia, shortened long bones, and short metacarpals and phalanges are common findings on radiological examination. Additionally, anterior tonguing of the vertebral bodies in the lateral view is an important finding in childhood because it is specific to PSACH and normalizes with age. Here, we report five Japanese patients with PSACH, with one recurrent (p.Cys351Tyr) and four novel heterozygous pathogenic COMP variants (p.Asp437Tyr, p.Asp446Gly, p.Asp507Tyr, and p.Asp518Val). These five pathogenic variants were located in the calcium-binding type 3 (T3) repeats. In four of the novel variants, the affected amino acid was aspartic acid, which is abundant in each of the eight T3 repeats. We describe the radiological findings of these five patients. We also retrospectively analyzed the sequential changes in the vertebral body and epimetaphysis of the long bones from the neonatal to infantile periods in a patient with PSACH and congenital heart disease.No potential conflict of interest relevant to this article was reported.RwActa Medica Okayama0030-155813432022`176179ENKoseiHasegawaDepartment of Pediatrics, Okayama University HospitalNatsukoFutagawaDepartment of Pediatrics, Okayama University HospitalHiroyukiMiyaharaDepartment of Pediatrics, Okayama University HospitalHirokazuTsukaharaDepartment of Pediatrics, Okayama University HospitalNo potential conflict of interest relevant to this article was reported.Nature PortfolioActa Medica Okayama2045-23221212022Thioredoxin interacting protein protects mice from fasting induced liver steatosis by activating ER stress and its downstream signaling pathways4819ENHiroyukiMiyaharaDepartment of Pediatrics, Okayama University HospitalKoseiHasegawaDepartment of Pediatrics, Okayama University HospitalMasatoYashiroDepartment of Pediatrics, Okayama University HospitalToshiakiOharaDepartment of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasayoshiFujisawaDepartment of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTeizoYoshimuraDepartment of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAkihiroMatsukawaDepartment of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHirokazuTsukaharaDepartment of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesUnder normal conditions, fasting results in decreased protein disulfide isomerase (PDI) activity and accumulation of unfolded proteins, leading to the subsequent activation of the unfolded protein response (UPR)/autophagy signaling pathway to eliminate damaged mitochondria. Fasting also induces upregulation of thioredoxin-interacting protein (TXNIP) expression and mice deficient of this protein (TXNIP-KO mice) was shown to develop severe hypoglycemia, hyperlipidemia and liver steatosis (LS). In the present study, we aimed to determine the role of TXNIP in fasting-induced LS by using male TXNIP-KO mice that developed LS without severe hypoglycemia. In TXNIP-KO mice, fasting induced severe microvesicular LS. Examinations by transmission electron microscopy revealed mitochondria with smaller size and deformities and the presence of few autophagosomes. The expression of beta-oxidation-associated genes remained at the same level and the level of LC3-II was low. PDI activity level stayed at the original level and the levels of p-IRE1 and X-box binding protein 1 spliced form (sXBP1) were lower. Interestingly, treatment of TXNIP-KO mice with bacitracin, a PDI inhibitor, restored the level of LC3-II after fasting. These results suggest that TXNIP regulates PDI activity and subsequent activation of the UPR/autophagy pathway and plays a protective role in fasting-induced LS.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1552-4825188A2021A novel pathogenic variant p.Asp797Val in IFIH1 in a Japanese boy with overlapping Singleton-Merten syndrome and Aicardi-Goutieres syndrome249252ENKoseiHasegawaDepartment of Pediatrics, Okayama University HospitalHiroyukiTanakaDepartment of Pediatrics, Okayama University Hospital NatsukoFutagawaDepartment of Pediatrics, Okayama University Hospital HiroyukiMiyaharaDepartment of Pediatrics, Okayama University HospitalYousukeHiguchiDepartment of Pediatrics, Okayama University HospitalHirokazuTsukaharaDepartment of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesPathogenic-activating variants of interferon induced with Helicase C domain 1 (IFIH1) cause Singleton-Merten (S-M) syndrome, which accompanies acro-osteolysis, loss of permanent teeth, and aortic calcification, as well as causing Aicardi-Goutières (A-G) syndrome, which shows progressive encephalopathy, spastic paraplegia, and calcification of basal ganglia. Recently, patients with overlapping syndromes presenting with features of S-M syndrome and A-G syndrome were reported. However, progression of clinical features of this condition has not been fully understood. We report a Japanese boy with a novel pathogenic IFIH1 variant who presented with clinical features of S-M syndrome and A-G syndrome.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2324-92692021Genetic analysis in Japanese patients with osteogenesis imperfecta: Genotype and phenotype spectra in 96 probandse1675ENYousukeHiguchiDepartment of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKoseiHasegawaDepartment of Pediatrics, Okayama University HospitalNatsukoFutagawaDepartment of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMihoYamashitaFaculty of Human Life Sciences, Notre Dame Seishin UniversityHiroyukiTanakaDepartment of Pediatrics, Okayama Saiseikai General HospitalHirokazuTsukaharaDepartment of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground Osteogenesis imperfecta (OI) is a rare connective-tissue disorder characterized by bone fragility. Approximately 90% of all OI cases are caused by variants in COL1A1 or COL1A2. Additionally, IFITM5 variants are responsible for the unique OI type 5. We previously analyzed COL1A1/2 variants in 22 Japanese families with OI through denaturing high-performance liquid chromatography screening, but our detection rate was low (41%). Methods To expand the genotype-phenotype correlations, we performed a genetic analysis of COL1A1/2 and IFITM5 in 96 non-consanguineous Japanese OI probands by Sanger sequencing. Results Of these individuals, 54, 41, and 1 had type 1 (mild), type 2-4 (moderate-to-severe), and type 5 phenotypes, respectively. In the mild group, COL1A1 nonsense and splice-site variants were prevalent (n = 30 and 20, respectively), but there were also COL1A1 and COL1A2 triple-helical glycine substitutions (n = 2 and 1, respectively). In the moderate-to-severe group, although COL1A1 and COL1A2 glycine substitutions were common (n = 14 and 18, respectively), other variants were also detected. The single case of type 5 had the characteristic c.-14C>T variant in IFITM5. Conclusion These results increase our previous detection rate for COL1A1/2 variants to 99% and provide insight into the genotype-phenotype correlations in OI.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0887-89941132020Pyridoxal in the Cerebrospinal Fluid May Be a Better Indicator of Vitamin B6–dependent Epilepsy Than Pyridoxal 5-Phosphate3341ENTomoyukiAkiyamaDepartment of Child Neurology, Okayama University HospitalYukiHyodoDepartment of Child Neurology, Okayama University HospitalKoseiHasegawaDepartment of Pediatrics, Okayama University HospitalTaikanOboshiDepartment of Pediatric Neurology, Osaka Womenfs and Childrenfs HospitalKatsumiImaiDepartment of Pediatrics, NHO Shizuoka Institute of Epilepsy and Neurological DisordersNaokoIshiharaDepartment of Pediatrics, Fujita Health University School of MedicineYuriDowaDepartment of Neurology, Gunma Childrenfs Medical CenterTakayoshiKoikeDepartment of Pediatrics, NHO Shizuoka Institute of Epilepsy and Neurological DisordersToshiyukiYamamotoInstitute of Clinical Genomics, Tokyo Womenfs Medical UniversityJunShibasakiDepartment of Neonatology, Kanagawa Childrenfs Medical CenterHirokoShimboClinical Institute, Kanagawa Childrenfs Medical CenterTetsuhiroFukuyamaDepartment of Pediatrics, Shinshu UniversityKyokoTakanoCenter for Medical Genetics, Shinshu University HospitalHiroshiShirakuDepartment of Pediatrics, JA Toride Medical CenterSaokoTakeshitaDepartment of Pediatrics, Yokohama City University Medical CenterTohruOkanishiDepartment of Child Neurology, Comprehensive Epilepsy Center, Seirei Hamamatsu General HospitalShimpeiBabaDepartment of Child Neurology, Comprehensive Epilepsy Center, Seirei Hamamatsu General HospitalMasayaKubotaDivision of Neurology, National Center for Child Health and DevelopmentShin-ichiroHamanoDivision of Neurology, Saitama Childrenfs Medical CenterKatsuhiroKobayashiDepartment of Child Neurology, Okayama University HospitalBackground</br>
We aimed to demonstrate the biochemical characteristics of vitamin B6–dependent epilepsy, with a particular focus on pyridoxal 5-phosphate and pyridoxal in the cerebrospinal fluid.</br>
Methods</br>
Using our laboratory database, we identified patients with vitamin B6–dependent epilepsy and extracted their data on the concentrations of pyridoxal 5-phosphate, pyridoxal, pipecolic acid, -aminoadipic semialdehyde, and monoamine neurotransmitters. We compared the biochemical characteristics of these patients with those of other epilepsy patients with low pyridoxal 5-phosphate concentrations.</br>
Results</br>
We identified seven patients with pyridoxine-dependent epilepsy caused by an ALDH7A1 gene abnormality, two patients with pyridoxal 5-phosphate homeostasis protein deficiency, and 28 patients with other epilepsies with low cerebrospinal fluid pyridoxal 5-phosphate concentrations. Cerebrospinal fluid pyridoxal and pyridoxal 5-phosphate concentrations were low in patients with vitamin B6–dependent epilepsy but cerebrospinal fluid pyridoxal concentrations were not reduced in most patients with other epilepsies with low cerebrospinal fluid pyridoxal 5-phosphate concentrations. Increase in 3-O-methyldopa and 5-hydroxytryptophan was demonstrated in some patients with vitamin B6–dependent epilepsy, suggestive of pyridoxal 5-phosphate deficiency in the brain.</br>
Conclusions</br>
Low cerebrospinal fluid pyridoxal concentrations may be a better indicator of pyridoxal 5-phosphate deficiency in the brain in vitamin B6–dependent epilepsy than low cerebrospinal fluid pyridoxal 5-phosphate concentrations. This finding is especially helpful in individuals with suspected pyridoxal 5-phosphate homeostasis protein deficiency, which does not have known biomarkers.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1328-80676252020Laboratory changes during adrenocorticotropic hormone therapy associated with renal calcified lesions587592ENHiroyukiMiyaharaDepartment of Pediatrics, Okayama University HospitalTomoyukiAkiyamaDepartment of Child Neurology, Okayama University HospitalKoseiHasegawaDepartment of Pediatrics, Okayama University HospitalMariAkiyamaDepartment of Child Neurology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineMakioOkaDepartment of Child Neurology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineKatsuhiroKobayashiDepartment of Child Neurology, Okayama University HospitalHirokazuTsukaharaDepartment of Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineBackground</br>
Renal calcified lesions are known as one of the complications during adrenocorticotropic hormone (ACTH) therapy for intractable epilepsy. However, laboratory changes during the therapy or laboratory features of high]risk cases with renal calcified lesions are yet to be clarified.</br>
Methods</br>
In this study, 43 patients with West syndrome aged ≤2 years were included. We retrospectively reviewed age and body mass index at the beginning of ACTH therapy, as well as the amount of fluid intake, daily urinary volume, and laboratory data during therapy. In addition, we studied the urinary sediment of the cases with renal calcified lesions diagnosed by computed tomography.
Results
After initiating ACTH treatment, urinary calcium (Ca)/creatinine ratio and urinary pH increased within 2 weeks. Urinary crystals and renal tubular epithelial cells (RTECs) in urinary sediment were frequently found in most cases. Urinary Ca levels, proteinuria or frequency of urinary crystals, and number of RTECs in the urinary sediment were significantly higher in patients with epithelial casts (ECs) or hematuria than in patients without these findings. Among the seven patients who underwent abdominal CT, ECs or hematuria were found only in those with renal calcified lesions. These findings suggested that patients with ECs or hematuria were more likely to have calcified lesions.</br>
Conclusions</br>
The risk of renal calcified lesions increased after 2 weeks of ACTH treatment. Abnormal findings in urinary sediments might be an early sign of renal calcification during ACTH therapy.No potential conflict of interest relevant to this article was reported.Japanese Society for Pediatric EndocrinologyActa Medica Okayama0918-57392842019Novel AVPR2 variant in a male infant with nephrogenic diabetes insipidus who showed delayed head control155158ENKoseiHasegawaDepartment of Pediatrics, Okayama University HospitalHiromiIhoriyaAdvanced Critical Care and Emergency Center, Okayama University HospitalNatsukoFutagawaDepartment of Pediatrics, Okayama University HospitalYousukeHiguchiDepartment of Pediatrics, Okayama University Hospital, Okayama, JapanHirokiTsuchiyaDepartment of Child Neurology, Okayama University HospitalTakashiShibataDepartment of Child Neurology, Okayama University HospitalYumikoHayashiDepartment of Child Neurology, Okayama University HospitalKatsuhiroKobayashiDepartment of Child Neurology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesHirokazuTsukaharaDepartment of Pediatrics, Okayama University Graduate School of Medicine Dentistry, and Pharmaceutical SciencesNo potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7062016Urinary Cross-linked N-terminal Telopeptide of Type I Collagen Levels of Infants with Osteogenesis Imperfecta and Healthy Infants435439ENMihoYamashitaDepartment of Pediatrics, Okayama University HospitalKoseiHasegawaDepartment of Pediatrics, Okayama University HospitalYousukeHiguchiDepartment of Pediatrics, Okayama University HospitalTakayukiMiyaiDepartment of Pediatrics, Okayama University HospitalAyumiOkadaOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroyukiTanakaDepartment of Pediatrics, Okayama Saiseikai General HospitalHirokazuTsukaharaOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOriginal Article10.18926/AMO/54805The urinary cross-linked N-terminal telopeptide of type I collagen (uNTx) levels in infantile osteogenesis imperfecta (OI) have not been well studied. Here we investigated the levels of uNTx in infants with OI and healthy infants. We collected spot urine samples from 30 infants with OI (male/female, 14/16; Sillence classification, I/II/III/IV: 15/3/6/6; age, 5.2}4.4 months) and 120 healthy infants (male/female, 75/45; age, 5.1}4.1 months) for the measurement of uNTx levels. The uNTx levels of the OI infants were significantly lower than those of the healthy infants (mean}SD, 1,363.7}530.1 vs. 2,622.2}1,202.6 nmol BCE/mmol Cr; p0.001). The uNTx levels of the infants with type I OI were significantly lower than those of the age-matched healthy infants, although an overlap was observed between the 2 groups. Among the 1-month-old infants, the uNTx levels of the infants with types I, III or IV OI were significantly lower than those of the healthy infants, without overlap (1,622.5}235.8 vs. 3,781.0}1,027.1 nmol BCE/mmol Cr; p0.001). These results indicate that uNTx levels are significantly lower in infants with OI than in healthy infants, and they suggest that uNTx might be useful as a reference for diagnosing OI.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2008Impaired Pyridinoline Cross-link Formation in Patients with@Osteogenesis ImperfectaENKoseiHasegawaNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2004A-KINASE ANCHORING PROTEIN 3 MESSENGER RNA EXPRESSION IN OVARIAN CANCER AND ITS IMPLICATION ON PROGNOSISENKoseiHasegawaNo potential conflict of interest relevant to this article was reported.