Effects of Multidisciplinary Health Promotion Program Among Children in Community Childcare Center.

In this study, the effects of a 12-month multidisciplinary education program on the health status, dietary quality, and eating habits of children and adolescents attending community childcare centers were investigated. A total of 88 participants aged 7 to 17 years from 7 community childcare centers in Gyeonggi-do were enrolled. The intervention consisted of 12 multidisciplinary education sessions covering topics such as nutrition, exercise, and psychological education. All participants received the same education, and the effectiveness of the program was evaluated by categorizing them into a high participation group (HPG) and a low participation group (LPG) based on their participation rates. After intervention, in physical activities, moderate-intensity exercise was significantly reduced in the LPG, and there was no significant difference in psychological parameters. However, notable differences were observed in nutritional data. After intervention, intakes of calorie, carbohydrate, protein, and fat were significantly increased in both groups, and in particular, the change was found to be greater in HPG. Additionally, dietary fiber intake compared to the 2015 Korean Dietary Reference Intakes was increased in both groups. Daily food intake also increased dietary fiber intake in HPG, and meat and fruit intake was increased in LPG. In the nutrition quotient, there was a significant difference in HPG's pre- and post-scores in the diversity category, and in nutrient adequacy ratio (NAR), the NAR of phosphorus was increased in both groups. The findings of this study suggest that multidisciplinary education implemented at community childcare centers primarily enhanced nutrition-related factors rather than physical activity or psychological aspects. Trial Registration: Clinical Research Information Service Identifier: KCT0002718.

Which obesity index is the most useful marker for predicting hepatic steatosis in children and adolescents with obesity? A cross-sectional study using quantitative magnetic resonance imaging.

INTRODUCTION: We aimed to evaluate the relationships between hepatic steatosis and various indices of obesity, and to identify the most useful index for the prediction of hepatic steatosis in children and adolescents with obesity. METHODS: A total of 226 children and adolescents with a mean body mass index (BMI) z-score of 2.65 and a mean age of 11.4 years were subjected to anthropometric and body composition measurements, laboratory testing, abdominal fat mass assessment, and hepatic fat accumulation by magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF). The participants were divided into quartiles according to the severity of their hepatic steatosis, and the presence of hepatic steatosis was defined using an MRI-PDFF ≥ 5%. RESULTS: The multivariate ordinal regression analysis showed that the severity of hepatic steatosis was positively associated with BMI, waist circumference, waist-to-hip ratio, waist-to-height ratio, fat mass, fat-free mass, visceral adiposity, and abdominal subcutaneous adiposity. Higher activities of liver enzymes and higher concentrations of triglyceride, C-reactive protein, fasting insulin, and leptin were associated with more severe hepatic steatosis, whereas high-density lipoprotein-cholesterol and adiponectin were negatively associated with hepatic steatosis. The indices of obesity with areas under the receiver operating characteristic curves (AUCs) > 0.8 for the prediction of hepatic steatosis were liver enzymes, visceral adipose tissue area, waist-to-hip ratio, and waist-to-height ratio. CONCLUSION: The severity of hepatic steatosis significantly correlated with various indices of obesity and cardiometabolic markers in children and adolescents with obesity. The indices of abdominal obesity would be the most useful for the prediction of hepatic steatosis.

Clinical and genetic analyses of patients with lateralized overgrowth.

BACKGROUND: The genetic features and treatment strategies of lateralized overgrowth have been elusive. We performed this study to analyze the genetic characteristics and treatment results of propranolol- or alpelisib-treated patients with lateralized overgrowth. METHODS: Fifteen patients with lateralized overgrowth were involved. Clinical characteristics and whole-body magnetic resonance imaging (WB-MRI) findings were evaluated. Targeted exome sequencing with a gene panel of affected tissue and peripheral white blood cells was performed. Propranolol was administered and treatment results were evaluated. The PIK3CA inhibitor alpelisib was prescribed via a managed access program. RESULTS: The identified mutations were PIK3CA (n = 7), KRAS (n = 2), PTEN (n = 1), MAP2K3 (n = 1), GNAQ (n = 1), TBC1D4 (n = 1), and TEK (n = 1). Propranolol was prescribed in 12 patients, and 7 experienced mild improvement of symptoms. Alpelisib was prescribed in two patients with a PIK3CA mutation, and the reduction of proliferated masses after 1 year of treatment was proved by WB-MRI. CONCLUSIONS: Targeted exome sequencing identified various genetic features of lateralized overgrowth. Propranolol could be applied as an adjuvant therapy for reducing vascular symptoms, but a PIK3CA inhibitor would be the primary therapeutic strategy for PIK3CA-related overgrowth syndrome.

Evaluation of users' level of satisfaction for an artificial intelligence-based diagnostic program in pediatric rare genetic diseases.

The artificial intelligence (AI)-based genetic diagnostic program has been applied to genome sequencing to facilitate the diagnostic process. The objective of the current study was to evaluate the experience and level of satisfaction of participants using an AI-based diagnostic program for rare pediatric genetic diseases. The patients with neurodevelopmental disorders or hearing impairments, their guardians, and their physicians from 16 tertiary general hospitals were enrolled. The study period was from April 2020 to March 2021. A survey was designed to assess their experience and level of satisfaction. A total of 30 physicians and 243 patients and guardians (199 neurodevelopmental disorders and 44 hearing impairments) completed the survey. DNA samples of the subjects were collected through buccal swabs or blood collection: 211 subjects (86.8%) through buccal swab and 29 subjects (11.9%) through blood collection. Average turnaround time for result receipt was 57.54 ± 32.42 days. For the sampling method, 193 patients and guardians (81.1%) and 28 physicians (93.3%) preferred buccal swab. The level of satisfaction of the 2 groups participating in the AI-based diagnostic program was 8.31 ± 1.71 out of 10 in the patient and guardian group and 8.42 ± 1.23 in the physician group. Clinicians, patients, and guardians are satisfied with the AI-based diagnostic program in general. With an increase in AI-based precision medicine solutions, the evaluation of the user's satisfaction with appropriate provision will help improve personal health care.

Vascular Alterations Preceding Arterial Wall Thickening in Overweight and Obese Children.

BACKGROUND: Childhood obesity is linked to adverse cardiovascular outcomes in adulthood. This study aimed to assess the impact of childhood obesity on the vasculature and to investigate whether vascular alteration precedes arterial wall thickening in childhood. METHODS: A total of 295 overweight (body mass index [BMI] 85th to 95th percentile, n = 30) and obese (BMI ≥ 95th percentile, n = 234) children aged 7-17 years and 31 normal-weight controls with similar age and gender were prospectively recruited. We assessed anthropometric data and laboratory findings, and measured the carotid intima-media thickness (IMT), carotid artery (CA) diameter, M-mode-derived arterial stiffness indices, and velocity vector imaging parameters, including the CA area, fractional area change, circumferential strain, and circumferential strain rate (SR). RESULTS: The mean ± standard deviation age of the participants was 10.8 ± 2.1 years; 172 (58%) children were male. Regarding structural properties, there was no difference in the IMT between the three groups. The CA diameter was significantly increased in obese children, whereas the CA area showed a significant increase beginning in the overweight stage. Regarding functional properties, contrary to ß stiffness and Young's elastic modulus, which were not different between the three groups, the circumferential SR showed a significant decrease beginning in the overweight stage and was independently associated with BMI z-scores after adjusting for covariates. CONCLUSION: We have demonstrated that arterial stiffening and arterial enlargement precede arterial wall thickening, and that these vascular alterations begin at the overweight stage in middle childhood or early adolescence.

Clinical and genetic features of four patients with Pearson syndrome: An observational study.

ABSTRACT: Pearson syndrome (PS) is a multisystem mitochondrial cytopathy arising from deletions in mitochondrial DNA. Pearson syndrome is a sporadic disease that affects the hematopoietic system, pancreas, eyes, liver, and heart and the prognosis is poor. Causes of morbidity include metabolic crisis, bone marrow dysfunction, sepsis, and liver failure in early infancy or childhood. Early diagnosis may minimize complications, but suspicion of the disease is difficult and only mitochondrial DNA gene testing can identify mutations. There is no specific treatment for PS, which remains supportive care according to symptoms; however, hematopoietic stem cell transplantation may be considered in cases of bone marrow failure.We herein describe the clinical and genetic characteristics of four patients with PS. One patient presented with hypoglycemia, two developed pancytopenia, and the final patient had hypoglycemia and acute hepatitis as the primary manifestation. All patients had lactic acidosis. Additionally, all patients showed a variety of clinical features including coagulation disorder, pancreatic, adrenal, and renal tubular insufficiencies. Two patients with pancytopenia died in their early childhood. Our experience expands the phenotypic spectrum associated with PS and its clinical understanding.

Additive Effects of Exercise or Nutrition Intervention in a 24-Month Multidisciplinary Treatment with a Booster Intervention for Children and Adolescents with Overweight or Obesity: The ICAAN Study.

This study compared the effects of a real-world multidisciplinary intervention with additional exercise or nutritional elements and investigated the effectiveness of a booster intervention after weight regain. A total of 242 children and adolescents (age- and sex-specific body mass index [BMI] ≥ 85th percentile, mean age: 10.82 years, 60% male) were allocated to three groups: usual care, exercise, or nutrition. Six-month active treatment with 1:1 session and a maintenance stage with group activities were repeated twice to comprise a 24-month intervention. The primary outcome was change % of the BMI z-score (zBMI). A total of 110 (45.4%) participants completed the 24-month intervention. A mixed-effects model analysis indicated no significant interaction effect of the intervention group and treatment phase on the zBMI change % (p = 0.976). However, there was a significant main effect of the treatment phase on zBMI change % at 6 months (ß = -2.98, [95% CI, -5.69-0.27]), 18 months (ß = -3.99, [95% CI, -6.76-1.22]), and 24 months (ß = -3.23, [95% CI, -5.94-0.52]; p = 0.042). The improvements in zBMI, body fat %, and cardiometabolic markers were observed only among males. Whereas the additive effect of intensive exercise or nutritional feedback was not detected in the long term, a booster intervention with 1:1 counseling was effective even after weight regain during the maintenance period. It may be useful to combine individualized counseling with a less intensive form of group care for long-term maintenance in a real-world setting.

Whole-body MRI evaluation in neurofibromatosis type 1 patients younger than 3 years old and the genetic contribution to disease progression.

BACKGROUND: Neurofibromatosis type 1 (NF1) is a common human genetic disease with age-dependent phenotype progression. The overview of clinical and radiological findings evaluated by whole-body magnetic resonance imaging (WBMRI) in NF1 patients < 3 years old assessed with a genetic contribution to disease progression is presented herein. METHODS: This study included 70 clinically or genetically diagnosed NF1 patients who received WBMRI before 3 years old. Clinical, genetic, and radiologic features were collected by retrospective chart review. In NF1+, widely spread diffuse cutaneous neurofibromas, developmental delay, autism, seizure, cardiac abnormalities, hearing defect, optic pathway glioma, severe plexiform neurofibromas (> 3 cm in diameter, disfigurement, accompanying pain, bony destruction, or located para-aortic area), brain tumors, nerve root tumors, malignant peripheral nerve sheath tumors, moyamoya disease, and bony dysplasia were included. RESULTS: The age at WBMRI was 1.6 ± 0.7 years old, and NF1 mutations were found in 66 patients (94.3%). Focal areas of signal intensity (FASI) were the most common WBMRI finding (66.1%), followed by optic pathway glioma (15.7%), spine dural ectasia (12.9%), and plexiform neurofibromas (10.0%). Plexiform neurofibromas and NF1+ were more prevalent in familial case (28.7% vs 5.7%, p = 0.030; 71.4% vs 30.2%, p = 0.011). Follow-up WBMRI was conducted in 42 patients (23 girls and 19 boys) after 1.21 ± 0.50 years. FASI and radiologic progression were more frequent in patients with mutations involving GTPase activating protein-related domain (77.8% vs 52.4%, p = 0.047; 46.2% vs 7.7%, p = 0.029). CONCLUSIONS: WBMRI provides important information for the clinical care for young pediatric NF1 patients. As NF1 progresses in even these young patients, and is related to family history and the affected NF1 domains, serial evaluation with WBMRI should be assessed based on the clinical and genetic features for the patients' best care.

Factors associated with dropout in a lifestyle modification program for weight management in children and adolescents.

BACKGROUND: Significant dropout rates remain a serious concern in pediatric weight control program, but few studies have identified predictors of dropout. AIMS: The objective of the study is to identify factors associated with dropout from a pediatric lifestyle modification weight control program at different phases. METHODS: Data on overweight and obese participants (n = 242) aged 11-18 years in the Intervention for Childhood and Adolescent Obesity via Activity and Nutrition (ICAAN) study were collected at baseline, 6-months, and 24-months through self-report and a laboratory test. Logistic regression analysis was performed for those who dropped out during the first 6-months, and multivariate generalized estimating equation analysis identified longitudinal factors associated with those who dropped out after 24 months. RESULTS: Lower family functioning (OR = 2.30, 95% CI [1.18-4.46]), exercise group (OR = 0.36, 95% CI [0.15-0.86]), lower initial attendance rate (OR = 6.09, 95% CI [2.94-12.6]), and non-self -referral pathways (OR = 2.35, 95% CI [1.05-5.27]) were significantly associated with 6-month dropouts. For late dropout, lower family functioning (OR = 1.71, 95% CI [1.06-2.77]) and lower initial attendance rates (OR = 2.06, 95% CI [1.12-3.81]) remained significant. CONCLUSION: Family function and initial attendance rate were associated with lower dropout rates. Developing a supportive family environment and focusing on the early-stage factors at the intervention's outset may reduce overall dropout rates in obesity prevention intervention.

Phenotype categorization of neurofibromatosis type I and correlation to NF1 mutation types.

Neurofibromatosis type 1 (NF1) is caused by heterozygous mutation in the NF1 gene. NF1 is one of the most common human genetic diseases. However, the overall genotype-phenotype correlation has not been known, due to a wide spectrum of genotypic and phenotypic heterogeneity. Here we describe the detailed clinical and genetic features of 427 Korean NF1 patients from 389 unrelated families. Long range PCR and sequencing of genomic DNA with multiplex ligation-dependent probe amplification analysis identified 250 different NF1 mutations in 363 families (93%), including 94 novel mutations. With an emphasis on phenotypes requiring medical attention (classified and termed: NF1+), we investigated the correlation of NF1+ and mutation types. NF1+ was more prevalent in patients with truncating/splicing mutations and large deletions than in those with missense mutations (59.6%, 64.3% vs. 36.6%, p = 0.001). This difference was especially significant in the patients younger than age 19 years. The number of items in NF1+ was a higher in the former groups (0.95 ± 0.06, 1.18 ± 0.20 vs. 0.56 ± 0.10, p = 0.002). These results suggest that mutation types are associated not only with higher prevalence of severe phenotypes in NF1 but also with their earlier onset.

Pharmacologic properties of high-dose ambroxol in four patients with Gaucher disease and myoclonic epilepsy.

BACKGROUND: Ambroxol (ABX) has been suggested as an augmentative pharmacological agent for neuronopathic Gaucher disease (nGD). This study assessed the long-term safety and efficacy of combined therapy with high-dose ABX and enzyme replacement therapy (ERT) in nGD. METHODS: ABX+ERT therapy was administered for 4.5 years in four patients with nGD. ABX was initiated at a dose of 1.5 mg/kg/day, and the dose was escalated up to 27 mg/kg/day. The target plasma level was 10 µmol/L or less. The changes in glucocerebrosidase activity, biochemical, safety and neurocognitive findings were assessed. RESULTS: Enhanced residual GCcase activity was observed in all patients, as evidenced in both in vitro and in vivo studies. During the first 2 years of study with ABX (up to 21 mg/kg/day), mean seizure frequencies and neurocognitive function worsened. After ABX dosage was increased up to 27 mg/kg/day of ABX, its trough plasma concentration was 3.2-8.8 µmol/L. Drug-to-drug interaction, especially with antiepileptic drug significantly affected the pharmacokinetic parameters of ABX. Importantly, at 27 mg/kg/day of ABX, the seizure frequencies markedly decreased from the baseline, and the neurocognitive function was improved. In addition, Lyso-Gb1, a biomarker for the severity and progression of GD, was normalised in all patients. High-dose ABX was well-tolerated with no severe adverse events. CONCLUSIONS: Long-term treatment with high-dose ABX+ERT was safe and might help to arrest the progression of the neurological manifestations in GD.

Evidence-based Nutritional Intervention Protocol for Korean Moderate-Severe Obese Children and Adolescents.

Diet-related behavioral modification for healthy eating and lifestyle is required to improve childhood obesity. The present study aimed to develop customized nutritional intervention protocol and education program to find barriers to adhere healthy diet and lifestyle for moderate to severe obese children and adolescents and their families. Theoretical framework approaches can be used to change behavior and achieve goals. Previous studies that described the relationship between behavioral modification and nutrition education theory were reviewed. The social cognitive theory and transtheoretical model were employed with behavioral changes to target a healthful diet and lifestyle. The nutrition care process (NCP) model was adopted to customize nutrition care for the participants. Customized nutritional intervention protocol was developed following as the four steps of the NCP. Firstly, nutrition status of the participants was assessed by the nutrition expert. Nutrition problems were described as "inadequate energy intake," "overweight/obesity," or "food and nutrition-related knowledge deficit." All nutrition sessions were designed for nutrition intervention to give nutritional knowledge and a practical mission in real life for individual goal setting and self-control. Meal planning, portion control, healthy snack selection and cooking with fruits and vegetables were consisted of five components of the nutrition education session. During each session, the participants and their families were interviewed by a nutrition expert for monitoring and evaluating diet-related goal setting and achievement. A theoretical and evidence-based nutritional intervention was developed for the secondary to tertiary prevention of childhood obesity. This nutrition intervention protocol and program might be helpful for the further research on childhood obesity. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0002111.

Association between Physical Fitness and Cardiometabolic Risk of Children and Adolescents in Korea.

BACKGROUND: This study aimed to investigate the association between physical fitness and cardiometabolic health of Korean children and adolescents. METHODS: In total, 168 participants (89 boys and 79 girls) aged 10-16 years were recruited for the Intervention for Childhood and Adolescent Obesity via Activity and Nutrition Study in 2016. The subjects were categorized into two groups using the definition of metabolic syndrome by the International Diabetes Federation: metabolically unhealthy (with at least two of the five criteria) and healthy groups (with less than one criterion). Correlation analysis of the participants' general characteristics was performed. Odds ratios (ORs) of physical fitness for cardiometabolic risk were evaluated via logistic regression. RESULTS: Metabolically unhealthy children showed greater weight, height, and body mass index, higher Children's Depression Inventory score, and longer screen time than did the metabolically healthy children. Metabolically healthy children showed greater upper and lower extremity muscular strength than did the metabolically unhealthy children (P=0.04 and P<0.001, respectively). In the multiple logistic regression analysis, lower extremity muscle strength was inversely related to the clustered cardiometabolic risk of the children and adolescents with or without adjustment for confounders (OR, 4.32; 95% confidence interval [CI], 1.87-9.97; OR, 7.64; 95% CI, 1.55- 37.74, respectively). CONCLUSION: Physical fitness, especially lower extremity muscle strength, is significantly inversely associated with individual and clustered cardiometabolic risks in Korean children and adolescents.

Pubertal outcomes and sex of rearing of patients with ovotesticular disorder of sex development and mixed gonadal dysgenesis.

PURPOSE: Patients with ovotesticular disorder of sex development (DSD) and mixed gonadal dysgenesis (MGD) usually present with asymmetric gonads and have wide phenotypic variations in internal and external genitalia. The differential diagnosis of these conditions is based on karyotype and pathological findings of the gonads. This study investigated the clinical features at presentation, karyotype, sex of rearing, and pubertal outcomes of patients with ovotesticular DSD and MGD. METHODS: The study comprised 23 patients with DSD who presented with asymmetric gonads. The presenting features, karyotype, sex of rearing, and pubertal outcomes were reviewed retrospectively. RESULTS: All 23 patients presented with ambiguous genitalia at a median age of 1 month (range, 1 day-1.6 years). Müllerian duct remnants were identified in 15 of 23 patients (65.2%). Fourteen patients were diagnosed with ovotesticular DSD, whereas the other 9 were diagnosed with MGD. Eight of 14 patients (57.1%) with ovotesticular DSD were raised as males, while 7 of 9 patients with MGD (77.8%) were assigned as males. One male-assigned patient with ovotesticular DSD changed to female sex at age 20 years. CONCLUSION: Patients with ovotesticular DSD and MGD manifest overlapping clinical presentations and hormonal profiles. It is difficult to determine the sex of rearing and predict long-term pubertal outcomes. Therefore, long-term follow-up is required to monitor spontaneous puberty, sex outcome, and urological and gynecological complications.

Low prevalence of argininosuccinate lyase deficiency among inherited urea cycle disorders in Korea.

Argininosuccinic aciduria (ASA), which is considered to be the second most common urea cycle disorder (UCD), is caused by an argininosuccinate lyase deficiency and is biochemically characterized by elevation of argininosuccinic acid and arginine deficiency. In addition to hyperammonemia, other characteristic features of ASA include hepatic fibrosis, hypertension, neurocognitive deficiencies, and trichorrhexis nodosa. Herein, we retrospectively reviewed the clinical findings, biochemical profiles, and genotypic characteristics of five Korean patients with ASA, who showed typical phenotypes and biochemical findings of the disease. Molecular analysis of these patients revealed six novel ASL mutations. Next, we investigated the prevalence of all types of UCDs in Korea. Of note, over a two decade periods, ASA was only detected in 6.3% of patients with a UCD, which made it the fourth most common UCD in Korea. In comparison with Caucasians, in whom ASA is the second most common UCD, ASA is comparatively rare in East Asian populations, including Japanese and Koreans. These findings suggest the possibility of geographic variation in UCDs among ethnic groups.

The phenotypic heterogeneity of patients with Marfan-related disorders and their variant spectrums.

Marfan syndrome (MFS) and Loeys-Dietz syndrome (LDS) are the connective tissue disorders characterized by aortic root aneurysm and/or dissection and various additional features. We evaluated the correlation of these mutations with the phenotypes and determined the clinical applicability of the revised Ghent criteria.The mutation spectrum and phenotypic heterogeneities of the 83 and 5 Korean patients with suspected MFS and LDS were investigated as a retrospective manner. In patients with suspected MFS patients, genetic testing was conducted in half of 44 patients who met the revised Ghent criteria clinically and half of 39 patients who did not meet these criteria.Fibrillin1 gene (FBN1) variants were detected in all the 22 patients (100%) who met the revised Ghent criteria and in 14 patients (77.8%) who did not meet the revised Ghent criteria (P = .0205). Patients with mutations in exons 24-32 were diagnosed at a younger age than those with mutations in other exons. Ectopia lentis was more common in patients with missense mutations than in patients with other mutations. Aortic diameter was greater in patients with missense mutations in cysteine residues than in patients with missense mutations in noncysteine residues. Five LDS patients had either TGFBR1 or TGFBR2 variants, of which 1 patient identified TGFBR1 variant uncertain significance.The revised Ghent criteria had very high clinical applicability for detecting FBN1 variants in patients with MFS and might help in selecting patients with suspected MFS for genetic testing.

Biochemical and molecular characterisation of neurological Wilson disease.

BACKGROUND: To identify biochemical and genetic features that characterise neurological Wilson disease as a distinct disease subgroup. METHODS: Detailed biochemical profiles and genotypic characteristics of neurological (86 patients) and hepatic subgroups (233 patients) from 368 unrelated Korean families were analysed. RESULTS: Compared with patients in the hepatic subgroup, patients in the neurological subgroup had a later age at onset, a higher proportion with Kayser-Fleischer rings and higher serum creatinine levels, and a lower proportion with favourable outcome (62% vs 80%, P<0.016). At diagnosis, the neurological subgroup had lower serum ceruloplasmin (3.1±2.1 mg/dL vs 4.2±3.2 mg/dL, P<0.001), total copper (26.4±13.8 µg/dL vs 35.8±42.4 µg/dL, P=0.005), free copper (17.2±12.5 µg/dL vs 23.5±38.2 µg/dL, P=0.038) and urinary copper (280.9±162.9 µg/day vs 611.1±1124.2 µg/day, P<0.001) levels. Serum aspartate aminotransferase, alanine aminotransferase, gamma glutamyltransferase and total bilirubin levels, as well as prothrombin time, were also lower in the neurological subgroup. Liver cirrhosis was more common but mostly compensated in the neurological subgroup. Frameshift, nonsense or splice-site ATP7B mutations and mutations in transduction or ATP hinge domains (2.4% vs 23.1%, P=0.006) were less common in the neurological subgroup. CONCLUSION: The neurological subgroup had distinct clinical, biochemical and genetic profiles. Further studies are required to identify the factors, with or without association with copper metabolism, underlying the neurological presentation for which treatment needs to be targeted to improve the clinical outcome of this subgroup.

Clinical characteristics and treatment outcomes in Camurati-Engelmann disease: A case series.

BACKGROUND: Camurati-Engelmann disease is an extremely rare disease characterized by hyperostosis of multiple long bones. This condition is caused by heterozygous mutations in the TGFB1 gene. METHODS: We describe the clinical and genetic characteristics of 4 Korean patients with this rare disease diagnosed at Asan Medical Center in Korea between June 2012 and May 2016, to increase awareness about this condition among general physicians and orthopedists. The presenting features, biochemical findings, radiographic and nuclear imaging findings, molecular analysis, and treatment outcomes of 4 patients were reviewed retrospectively. RESULTS: Two patients had sporadic disease, whereas the other 2 were familial cases. The average age at symptom onset was 8.8 ±â€Š5.5 (4-14) years. Symptoms included waddling gait or leg pain. Bone pain and easy fatigability were documented in all patients. Skeletal deformities such as osteoporosis, genu valgum, and severe scoliosis were observed. Visual and otologic manifestations presenting as exophthalmos, retinal detachment, and vestibulopathy were found in 3 patients. Skeletal survey showed diaphyseal expansion with diffuse cortical thickening of long bones in all patients. Bone scintigraphy images showed increased uptake of radioactive material in the calvarium and diaphysis of long bones. The mean erythrocyte sedimentation rate was 46.5 ±â€Š22.2 (20-72) mm/h. Sequence analysis of TGFB1 revealed the previously reported mutations p.Arg218His, p.Arg218Cys, and p.Glu169Lys. Corticosteroid was effective in relieving pain, and losartan was used as maintenance therapy. CONCLUSIONS: Our experience suggests that this rare condition can be suspected in patients with characteristic symptoms and skeletal findings. Considering the presence of effective medical treatment, efforts are needed to identify more cases.

Biochemical and molecular analyses of infantile sialic acid storage disease in a patient with nonimmune hydrops fetalis.

Nonimmune hydrops fetalis is the most severe clinical manifestation of lysosomal storage diseases (LSDs). Around 14 different LSDs have been accounted for as 1-15% of the cause of nonimmune hydrops fetalis. We report a Korean infant affected by an extremely rare but severe form of sialic acid storage disease. The patient presented with nonimmune hydrops fetalis, dysmorphic facial features, hepatosplenomegaly, and dysostosis multiplex and died at 39 days of age due to persistent pulmonary hypertension. LSD was suspected based on the presence of diffuse vacuolation of syncytiotrophoblast, villous stromal cells, and intermediate trophoblast in placental biopsy. Increased excretion of urinary free sialic acid was detected by liquid chromatography-tandem mass spectrometry. The patient was compound heterozygous of the c.908G>A (p.Trp303Ter) and the splicing mutation c.1259+5G>T (IVS9+5 G>T) in the SLC17A5 gene.

Hepatopulmonary syndrome caused by hypothalamic obesity and nonalcoholic fatty liver disease after surgery for craniopharyngioma: a case report.

Hypothalamic obesity is often complicated in patients with craniopharyngioma due to hypothalamic damage by the tumor itself, treatment modalities, and associated multiple pituitary hormone deficiency. Hypothalamic obesity causes secondary diseases such as nonalcoholic fatty liver disease (NAFLD) and diabetes mellitus (DM). We report a 19-year-old female who was diagnosed with craniopharyngioma, developed hypothalamic obesity after tumor resection, and progressed to hepatopulmonary syndrome. She manifested NAFLD 1 year after tumor resection. Two years later, the craniopharyngioma recurred, and she underwent a second resection. Three years after her second operation, she was diagnosed with type 2 DM, after which she did not visit the outpatient clinic for 2 years and then suddenly reappeared with a weight loss of 25.8 kg that had occurred over 21 months. One month later, she presented to the Emergency Department with dyspnea. Laboratory findings revealed liver dysfunction and hypoxia with increased alveolar artery oxygen gradient. Liver biopsy showed portal hypertension and micronodular cirrhosis. Echocardiography and a lung perfusion scan demonstrated a right to left shunt. She was finally diagnosed with hepatopulmonary syndrome and is currently awaiting a donor for liver transplantation. Patients surviving craniopharyngioma need to be followed up carefully to detect signs of hypothalamic obesity and monitored for the development of other comorbidities such as DM, NAFLD, and hepatopulmonary syndrome.