Evaluation of the effects of a team-based systematic prevention and management program for postoperative orthopedic older patients: A retrospective cohort study.

Aim: This study aimed to evaluate a team-based systematic prevention and management program for delirium (a multicomponent intervention addressing potentially modifiable risk factors based on the DELirium Team Approach [DELTA]) in older patients undergoing orthopedic surgery within a real-world clinical setting. The DELTA program was initiated at our hospital in January 2019. Methods: A retrospective before-after study was conducted during a preintervention period (January 1, 2017 to December 31, 2018) and a postintervention period (January 1, 2020 to December 31, 2021) at orthopedic wards of an advanced acute care hospital in Japan. A total of 787 inpatients were evaluated before the preintervention period, and 833 inpatients were evaluated after the postintervention period. Results: After the DELTA program's implementation, a significant decrease in benzodiazepine receptor agonist prescriptions (odds ratio [OR], 0.39; 95% confidence interval [CI], 0.29-0.53) and an increase in prescriptions of either melatonin receptor agonists or dual orexin receptor antagonists (OR, 3.83; 95% CI, 2.49-5.88) were observed. However, no significant difference was observed in the incidence of falls, self-extubation, or required level of medical and nursing care, including risky behavior and inability to follow medical or care instructions following the intervention, despite a reduction in the length of hospital stay and institutionalization. Conclusion: Implementing the DELTA program for older patients undergoing orthopedic surgery contributed to optimizing the prescription of hypnotics; however, the impact on other patient outcomes, such as falls, self-extubation, and required level of medical and nursing care was limited.

An autopsy case of an adult woman with Rapid-Onset Obesity with Hypoventilation, Hypothalamic, Autonomic Dysregulation, and Neuroendocrine Tumors (ROHHAD(NET)) syndrome developing nonalcoholic steatohepatitis and hepatocellular carcinoma: A case report.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is an important etiology of hepatocellular carcinoma (HCC), and there is no established therapy for this syndrome. Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, autonomic dysregulation, and neural crest tumor (ROHHAD(NET)) is an extremely rare syndrome considered to be life-threatening, with death occurring around 10 years of age. We present the oldest known autopsy case of this syndrome that developed HCC. This case provided important information on not only improving the course of this syndrome, but also understanding the natural history and therapeutic modalities of NASH and HCC. METHODS: The patient was diagnosed with ROHHAD(NET) syndrome in childhood, and liver cirrhosis due to NASH was diagnosed at age 17. HCC was detected at age 20, and embolization and irradiation were performed. At age 21, she died from accidental acute pancreatitis and subsequent liver failure and pulmonary hemorrhage. RESULTS: Rapid onset of obesity, hypoventilation, and hypothalamic disturbance appeared in childhood and was diagnosed as this syndrome. At age 17, liver cirrhosis due to NASH was diagnosed by liver biopsy, and at age 20, HCC was diagnosed by imaging. Transarterial chemoembolization and irradiation were performed, and the HCC was well controlled for a year. CONCLUSION: At age 21, she died from accidental acute pancreatitis, subsequent liver failure and pulmonary hemorrhage. Autopsy revealed that the HCC was mostly necrotized. This case was valuable not only for other ROHHAD(NET) syndrome cases, but also in improving our understanding of the natural history of NASH and HCC.

A novel variant of IGSF1 in siblings with congenital central hypothyroidism whose diagnosis was prompted by school health checkups.

Following the partial revision of the enforcement regulations of the School Health and Safety Act, school health checkups incorporated growth evaluation of schoolchildren in April 2016 using growth charts. We report cases of congenital central hypothyroidism (C-CH) in siblings with a novel nonsense variant in the immunoglobulin superfamily member 1 gene (IGSF1); their diagnoses were prompted by school health checkups. School checkups revealed that the older brother was overweight and had a reduced growth rate at the age of 11 yr, whereas the younger brother was overweight and had short stature at the age of 8 yr. They were diagnosed with C-CH because of normal thyroid-stimulating hormone (TSH) levels despite a low free thyroxine level and low TSH response in the thyrotropin-releasing hormone stress test. Only the older brother had prolactin deficiency and testicular growth without elevated testosterone levels. The siblings harbored a novel nonsense variant in exon 16 of IGSF1 (NM_001555.5: c.3056G>A: p.Trp1019Ter) and were diagnosed with IGSF1 deficiency. In Japan, C-CH may be overlooked because TSH-based newborn screening alone is usually performed for patients with congenital hypothyroidism. The implementation of growth monitoring using growth charts in school health checkups may prompt new C-CH diagnoses.

Knowns and unknowns about congenital hypothyroidism: 2022 update.

Several excellent guidelines and expert opinions on congenital hypothyroidism (CH) are currently available. Nonetheless, these guidelines do not address several issues related to CH in detail. In this review, the authors chose the following seven clinical issues that they felt were especially deserving of closer scrutiny in the hope that drawing attention to them through discussion would help pediatric endocrinologists and promote further interest in the treatment of CH. 1. How high should the levothyroxine (L-T4) dose be for initial treatment of severe and permanent CH? 2. What is the optimal method for monitoring treatment of severe CH? 3. At what level does maternal iodine intake during pregnancy affect fetal and neonatal thyroid function? 4. Does serum thyroglobulin differ between patients with a dual oxidase 2 (DUOX2) variants and those with excess iodine? 5. Who qualifies for a genetic diagnosis? 6. What is the best index for distinguishing transient and permanent CH? 7. Is there any cancer risk associated with CH? The authors discussed these topics and jointly edited the manuscript to improve the understanding of CH and related issues.

Goiter in a 6-year-old patient with novel thyroglobulin gene variant (Gly145Glu) causing intracellular thyroglobulin transport disorder: Correlation between goiter size and the free T3 to free T4 ratio.

Thyroglobulin gene abnormalities cause thyroid dyshormonogenesis. A 6-yr-old boy of consanguineous parents presented with a large goiter and mild hypothyroidism (thyroid-stimulating hormone [TSH] 7.2 µIU/mL, free T3 [FT3] 3.4 pg/mL, free T4 [FT4] 0.6 ng/dL). Despite levothyroxine (LT4) administration and normal TSH levels, the goiter progressed slowly and increased rapidly in size at the onset of puberty. Thyroid scintigraphy revealed a remarkably high 123I uptake of 75.2%, with a serum thyroglobulin level of 13 ng/ml, which was disproportionately low for the goiter size. DNA sequencing revealed a novel homozygous missense variant, c.434G>A [p.Gly145Glu], in the thyroglobulin gene. Goiter growth was suppressed by increasing the LT4 dose. Thyroidectomy was performed at 17-yr-of-age. Thyroglobulin analysis of the thyroid tissue detected mutant thyroglobulin present in the endoplasmic reticulum, demonstrating that thyroglobulin transport from the endoplasmic reticulum to the Golgi apparatus was impaired by the Gly145Glu variant. During the clinical course, an elevated FT3/FT4 ratio was observed along with thyroid enlargement. A high FT3/FT4 ratio and goiter seemed to be compensatory responses to impaired hormone synthesis. Thyroglobulin defects with goiter should be treated with LT4, even if TSH levels are normal.

Psychosocial interventions for community-dwelling individuals with schizophrenia: study protocol for a systematic review and meta-analysis.

INTRODUCTION: Despite the recent global mental health movement of the transition from hospital-centred to integrated community-based services, comprehensive evidence of psychosocial interventions focusing on community-dwelling individuals with schizophrenia is still lacking. To overcome this gap in the current knowledge, we will conduct a systematic review and meta-analysis to assess the efficacy of all types of psychosocial interventions for community-dwelling (non-hospitalised) individuals with schizophrenia when compared with non-active control conditions (eg, treatment as usual). METHODS AND ANALYSIS: This study protocol has been developed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. By March 2022, the following sources will have been searched, without restrictions for language or publication period: Embase, PubMed, PsycINFO, CINAHL, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform. We will also try to identify other potentially eligible studies by searching the reference lists of included studies, other relevant systematic reviews and grey literature. All relevant randomised controlled trials from both high-income and low-income to middle-income countries will be allowed. Two independent reviewers will conduct the selection/screening of studies, data extraction and methodological quality assessment of included studies. The primary outcomes are quality of life and psychiatric hospital admission. Standard pairwise meta-analyses with a random-effects model will be conducted. Subgroup and sensitivity analyses will be performed to assess the robustness of the findings. Risk of bias will be assessed with the Revised Cochrane Risk-of-Bias Tool for Randomised Trials. The Grades of Recommendation Assessment, Development and Evaluation approach will be used to assess the quality of evidence. ETHICS AND DISSEMINATION: Ethics approval is not required for this study. The study findings will be disseminated through conference presentations as well as peer-reviewed publications. PROSPERO REGISTRATION NUMBER: CRD42021266187.

Novel TRPV6 mutations in the spectrum of transient neonatal hyperparathyroidism.

Maternal-fetal calcium (Ca2+) transport in the placenta plays a critical role in maintaining fetal bone mineralization. Mutations in the gene encoding the transient receptor potential cation channel, subfamily V, member 6 (TRPV6) have been identified as causative mutations of transient neonatal hyperparathyroidism due to insufficient maternal-fetal Ca2+ transport in the placenta. In this study, we found two novel mutations in subjects that have transient neonatal hyperparathyroidism. TRPV6 carrying the mutation p.Arg390His that localizes to the outer edge of the first transmembrane domain (S1) showed impaired trafficking to the plasma membrane, whereas TRPV6 having the mutation p.Gly291Ser in the sixth ankyrin repeat (AR) domain had channel properties that were comparable those of WT channels, although the increases in steady-state intracellular Ca2+ concentration could have led to Ca2+ overload and subsequent death of cells expressing this mutant channel. These results indicate that the AR6 domain contributes to TRPV6-mediated maintenance of intracellular Ca2+ concentrations, and that this region could play a novel role in regulating the activity of TRPV6 Ca2+-selective channels.

Newborn screening for Fabry disease in the western region of Japan.

Newborn screening (NBS) for Fabry disease (FD) is the best way to detect FD early prior to presentation of symptoms and is currently implemented in Taiwan and several states such as Illinois, Missouri, and Tennessee in the United States of America. In this report, we provide data from the first large-scale NBS program for FD in Japan. From August 2006 to December 2018, 599,711 newborns were screened; 26 variants, including 15 pathogenic variants and 11 variants of uncertain significance (VOUS; including eight novel variants), were detected in 57 newborns. Twenty-six male and 11 female newborns with pathogenic variants were diagnosed as hemizygous and heterozygous patients, respectively. Thirteen male and seven female newborns with VOUS were diagnosed as potential hemizygous and potential heterozygous patients, respectively. At the most recent follow up, three of 26 hemizygous patients had manifested symptoms and were receiving enzyme replacement therapy. The other patients were being followed up by clinicians. The frequency of FD (pathogenic variants + VOUS) in this study was estimated to be 1:7683, whereas that of patients with pathogenic variants was 1:11,854. In the future, the NBS system for FD may contribute to the detection of newborns not presenting manifestations related to FD and adults who have or have not developed manifestations related to FD.

Levothyroxine Dosage as Predictor of Permanent and Transient Congenital Hypothyroidism: A Multicenter Retrospective Study in Japan.

BACKGROUND: Congenital hypothyroidism (CH) can be divided into 2 types, transient CH (T-CH) and permanent CH (P-CH), depending on the requirement of levothyroxine (LT4) for life-long treatment. Several studies have recently reported that the LT4 dosage is useful for predicting the LT4 requirement, but none of the studies followed their patients to puberty. OBJECTIVE: To determine the cutoff value for the LT4 dosage as a predictor of the LT4 requirement after puberty in patients with CH. METHODS: The LT4 dosage and clinical data on 99 patients with CH who were followed at the participating hospitals from the neonatal period to 15 years of age or older were retrospectively analyzed. Based on their LT4 requirement at their last hospital visit, the participants were divided into the P-CH group (n = 75), who were treated with LT4, and the T-CH group (n = 24), who were not. RESULTS: At age 1 year, a higher LT4 dosage was required for the P-CH group (median 3.75 vs. 2.88 µg/kg/day; p < 0.001). When the LT4 dosage cutoff value at age 1 year was set at 4.79 and 1.74 µg/kg/day, the specificity of P-CH and T-CH (for denying T-CH and P-CH, respectively) was 100 and 97%, respectively. CONCLUSIONS: An LT4 dosage above 4.7 µg/kg/day and below 1.8 µg/kg/day at age 1 year may help predict P-CH and T-CH, respectively.

TRPV6 Gene Mutation in a Dizygous Twin With Transient Neonatal Hyperparathyroidism.

Maternal-fetal transport of calcium (Ca2+) is important for bone mineralization in fetal development. Insufficient Ca2+ transport causes transient neonatal hyperparathyroidism (TNHP). Transient receptor potential cation channel, subfamily V, member 6 (TRPV6), has been found to play an important role in the active transport of Ca2+ through the placenta. Recently, TRPV6 gene was found to be the gene responsible for TNHP with severe skeletal undermineralization. To date, only seven cases of TNHP caused by TRPV6 recessive mutations have been reported. We present a case of TNHP caused by TRPV6 gene mutations. A female newborn was hospitalized because of respiratory distress. Marked undermineralization of the skeleton was observed in X-ray imaging. Laboratory examination revealed markedly high PTH and absence of hypercalcemia along with vitamin D deficiency. Her twin brother presented with almost no symptoms. Maternal laboratory findings indicated normocalcemia, but vitamin D deficiency with a high PTH level for the lactation period was observed. We initially diagnosed the patient as having secondary hyperparathyroidism because of maternal vitamin D deficiency. Nevertheless, the reasons underlying the discordant clinical manifestations between the twin siblings remained unclear. Our analysis of TRPV6 gene clarified that the patient had compound heterozygote mutations, which were reported previously (p.Ile223Thr and p.Gly428Arg). Pathologic mutations in TRPV6 gene were not detected in the other sibling. The clinical symptoms in the patient were transient: they resolved during infancy. TNHP caused by TRPV6 gene mutations is a unique disease in terms of its transient pathology in utero and relief after birth.

TRPV6 Variants Interfere with Maternal-Fetal Calcium Transport through the Placenta and Cause Transient Neonatal Hyperparathyroidism.

Transient neonatal hyperparathyroidism (TNHP) is etiologically a heterogeneous condition. One of the etiologies is an insufficient maternal-fetal calcium transport through the placenta. We report six subjects with homozygous and/or compound-heterozygous mutations in the gene encoding the transient receptor potential cation channel, subfamily V, member 6 (TRPV6), an epithelial Ca2+-selective channel associated with this condition. Exome sequencing on two neonates with skeletal findings consistent with neonatal hyperparathyroidism identified homozygous frameshift mutations before the first transmembrane domain in a subject born to first-cousins parents of Pakistani descent as well as compound-heterozygous mutations (a combination of a frameshift mutation and an intronic mutation that alters mRNA splicing) in an individual born to a non-consanguineous couple of African descent. Subsequently, targeted mutation analysis of TRPV6 performed on four other individuals (born to non-consanguineous Japanese parents) with similar X-rays findings identified compound-heterozygous mutations. The skeletal findings improved or resolved in most subjects during the first few months of life. We identified three missense variants (at the outer edges of the second and third transmembrane domains) that alter the localization of the TRPV6: one recurrent variant at the S2-S3 loop and two recurrent variants (in the fourth ankyrin repeat domain) that impair TRPV6 stability. Compound heterozygous loss-of-function mutations for the pathogenic frameshift allele and the allele with an intronic c.607+5G>A mutation resulted in the most severe phenotype. These results suggest that TNHP is an autosomal-recessive disease caused by TRPV6 mutations that affect maternal-fetal calcium transport.

Incidence and Characteristics of Adrenal Crisis in Children Younger than 7 Years with 21-Hydroxylase Deficiency: A Nationwide Survey in Japan.

BACKGROUND/AIMS: We aimed to evaluate the incidence and characteristics of adrenal crisis in Japanese children with 21-hydroxylase deficiency (21-OHD). METHODS: We conducted a retrospective nationwide survey for the councilors of the Japanese Society for Pediatric Endocrinology (JSPE) regarding adrenal crisis in children under 7 years with 21-OHD, admitted to hospitals from 2011 through 2016. We defined adrenal crisis as the acute impairment of general health due to glucocorticoid deficiency with at least two of symptoms, signs, or biochemical abnormalities. RESULTS: The councilors of the JSPE in 83 institutions responded to this survey (response rate, 60.1%). Data analyses of 378 patients with 1,101.4 person-years (PYs) revealed that 67 patients (17.7%) experienced at least 1 episode of hospital admission for adrenal crisis at the median age of 2 years. The incidence of adrenal crisis was calculated as 10.9 per 100 PYs (95% confidence interval [CI] 9.6-12.2). Infections were the most common precipitating factors, while no factor was observed in 12.5%. Hypoglycemia occurred concomitantly in 27.4%. One patient died from severe hypoglycemia, resulting in a mortality rate of 0.09 per 100 PYs (95% CI 0.0-0.2). CONCLUSION: Adrenal crisis is not rare and can be accompanied by disastrous hypoglycemia in children with 21-OHD.

A hot-spot mutation in CDC42 (p.Tyr64Cys) and novel phenotypes in the third patient with Takenouchi-Kosaki syndrome.

Takenouchi-Kosaki syndrome (TKS) is a congenital malformation syndrome characterized by severe developmental delay, macrothrombocytopenia, camptodactyly, sensorineural hearing loss, and dysmorphic facial features. Recently, a heterozygous de novo mutation (p.Tyr64Cys) in the CDC42 gene, which encodes a key small GTP-binding protein of the Rho-subfamily, was identified in two unrelated patients with TKS. We herein report a third patient with TKS who had the same heterozygous CDC42 mutation. The phenotype of the patient was very similar to those of the two previously reported patients with TKS; however, she also demonstrated novel clinical manifestations, such as congenital hypothyroidism and immunological disturbance. Thus, despite the heterozygous mutation of CDC42 (p.Tyr64Cys) likely being a hot-spot mutation for TKS, its phenotype may be variable. Further studies and the accumulation of patients with CDC42 mutations are needed to clarify the phenotype in patients with TKS and the pathophysiological roles of the CDC42 mutation.

Clinical characteristics of septo-optic dysplasia accompanied by congenital central hypothyroidism in Japan.

Septo-optic dysplasia (SOD) is a congenital anomaly in which agenesis of the septum pellucidum and optic nerve hypoplasia are accompanied by hypopituitarism. Typically, the symptoms develop in 3 organs, the brain, eyes, and pituitary, and approximately one third of the patients present with all of the three cardinal features. The diagnostic criteria for SOD were established in Japan in 2015. The purpose of this study is to review clinical features regarding SOD patients with hypopituitarism in Japan. In this study, 21 patients with SOD were identified by a questionnaire survey for congenital central hypothyroidism. All 3 symptoms of SOD, agenesis of the septum pellucidum, optic nerve hypoplasia, and endocrine abnormalities, were noted in 8 of the 21 patients. Various combinations of pituitary hormone deficiencies were observed in patients with SOD, although SOD is a rare, heterogeneous, and phenotypically variable disorder, some patients develop hypoglycemia and convulsions after birth, and early intervention with hormone replacement is necessary in severe cases. In addition, 14 cases were complicated by both developmental delay and epilepsy, and 16 cases involved eye abnormalities. Therefore, in addition to an early endocrinological diagnosis and hormone replacement, consultation with both pediatric neurologists and pediatric ophthalmologists is necessary.

Molecular and clinical features of KATP -channel neonatal diabetes mellitus in Japan.

BACKGROUND: There are few reports pertaining to Asian patients with neonatal diabetes mellitus (NDM) caused by activating mutations in the ATP-sensitive potassium channel genes (KATP-NDM). OBJECTIVES: To elucidate the characteristics of Japanese patients with KATP-NDM. METHODS: By the amplification and direct sequencing of all exons and exon-intron boundaries of the KCNJ11 and ABCC8 genes, 25 patients with KATP-NDM were identified from a total of 70 patients with NDM. Clinical data were collected from the medical charts. RESULTS: Sixteen patients had mutations in KCNJ11 and nine in ABCC8. Eight novel mutations were identified; two in KCNJ11 (V64M, R201G) and six in ABCC8 (R216C, G832C, F1176L, A1263V, I196N, T229N). Interestingly, V64M caused DEND (developmental delay, epilepsy, neonatal diabetes) syndrome in our patient, while mutation of the same residue (V64G) had been reported to cause congenital hyperinsulinism. Mutations in ABCC8 were associated with TNDM (4/9) or isolated PNDM (5/9), whereas those in KCNJ11 were associated with more severe phenotypes, including DEND (3/16), iDEND (intermediate DEND, 4/16), or isolated PNDM (6/16). Switching from insulin to glibenclamide monotherapy was successful in 87.5% of the patients. Neurological improvement was observed in two patients, one with DEND (T293N) and one with iDEND (R50P) syndrome. Three others with iDEND mutations (R201C, G53D, and V59M) remained neurologically normal at 5, 1, and 4 years of age, respectively, with early introduction of sulfonylurea. CONCLUSION: Overall, clinical presentation of KATP-NDM in Japanese patients was similar to those of other populations. Early introduction of sulfonylurea appeared beneficial in ameliorating neurological symptoms.

Development of a novel ultrasensitive enzyme immunoassay for human glutamic acid decarboxylase 65 antibody.

BACKGROUND: We developed a novel, ultrasensitive enzyme immunoassay (immune complex transfer enzyme immunoassay) for determination of glutamic acid decarboxylase autoantibody concentrations in serum samples from patients with type 2 diabetes. METHODS: We developed an immune complex transfer enzyme immunoassay for glutamic acid decarboxylase autoantibody and measured glutamic acid decarboxylase autoantibody from 22 patients with type 1 diabetes, 29 patients with type 2 diabetes, and 32 healthy controls. RESULTS: A conventional ELISA kit identified 10 patients with type 1 diabetes and one patient with type 2 diabetes as glutamic acid decarboxylase autoantibody positive, whereas 15 patients with type 1 diabetes and six patients with type 2 diabetes were identified as glutamic acid decarboxylase autoantibody positive using immune complex transfer enzyme immunoassay. CONCLUSIONS: Immune complex transfer enzyme immunoassay is a highly sensitive and specific assay for glutamic acid decarboxylase autoantibody and might be clinically useful for diabetic onset prediction and early diagnosis.

Living donor liver transplantation from a heterozygous parent for classical maple syrup urine disease.

MSUD is a hereditary metabolic disorder that is characterized by impaired activity of the BCKADC. Liver transplantation has been approved as a treatment for some MSUD cases in which the control of BCAAs is insufficient. Although there have been several reports about DDLT for MSUD, few LDLT cases have been reported. Because either of parents who are heterozygote of this disease usually applies to be a candidate of donor in LDLT, the impairment of BCKADC activity of graft liver should be concerned. We performed LDLT for 10 month-old girl with a left lateral segment graft from her father. BCKADC activities of the patient and her parents were measured using lysates of lymphocytes isolated from peripheral blood specimen before the transplant. As a consequence, the activity of BCKADC of father was not inferior to a normal range. The patient tolerated the operation well. Postoperative course was uneventful and mixed milk was started at 8th POD. The serum BCAAs levels have remained within normal range. It should be necessary to follow the physical growth and mental development of the recipient in the future.

Infantile Cases of Sitosterolaemia with Novel Mutations in the ABCG5 Gene: Extreme Hypercholesterolaemia is Exacerbated by Breastfeeding.

Few data exists regarding the clinical impact of breastfeeding in infantile sitosterolaemic cases. We report four Japanese infantile cases of sitosterolaemia, an extremely rare inherited disease characterised by increased serum levels of plant sitosterol, presenting with severe hypercholesterolaemia and systemic xanthomas exacerbated by breastfeeding. In these four cases, genetic analyses were performed for low-density lipoprotein (LDL) receptor, proprotein convertase subtilisin/kexin type 9 (PCSK9), LDL receptor adaptor protein 1 and ATP-binding cassette (ABC) subfamily G member 5 and 8 (ABCG5 and ABCG8) genes. We assessed their clinical manifestations, including responsiveness to a variety of treatments, especially to weaning from breastfeeding and use of ezetimibe. Two pairs of mutations in the ABCG5 gene in each case, including two novel mutations (c.130C>T or p.Ser44Ala and c.1813_1817delCTTTT or p.Pro558GlufsX14) and two known mutations (c.1306G>A or p.Arg389His and c.1336C>T or p.Arg446X), were identified. Significant reductions in cholesterol levels were obtained by means of weaning from breastfeeding alone. Substantial reductions in sitosterol levels, without any apparent side effects, were observed with ezetimibe. In conclusion, we have identified infantile Japanese sitosterolaemic subjects with extreme hypercholesterolaemia exacerbated by breastfeeding. Their unique response to weaning from breastfeeding, as well as to use of ezetimibe, could provide insights into the metabolic basis of sterols in humans.

Nephrotic syndrome complicated by idiopathic central diabetes insipidus.

BACKGROUND: There is ongoing discussion regarding the mechanisms underlying edema formation in nephrotic syndrome (NS). Many studies published in the last decade reported that primary renal sodium retention was a major factor in edema formation. However, many of the factors influencing edema formation in NS remain unclear, including the role of arginine vasopressin (AVP). CASE-DIAGNOSIS/TREATMENT: We report a 12-year-old boy with steroid-dependent NS complicated by idiopathic central diabetes insipidus (CDI). He did not develop edema during his first relapse of NS after developing CDI, despite having hypoalbuminemia. He had polydipsia, polyuria, low urine osmolality, and a low serum arginine AVP level. His fractional excretion of sodium was only slightly low. Endocrinological testing and magnetic resonance imaging revealed idiopathic CDI. After starting desmopressin therapy, he developed edema when his NS relapsed. CONCLUSIONS: This is the first known reported case of NS in a patient with CDI. The findings suggest that appropriate AVP secretion in response to an increase in serum osmolality caused by renal sodium retention is necessary for excess extracellular fluid accumulation in NS. Further investigation is needed to more fully understand the role of AVP in edema formation in NS.