Expanding the neuroimaging findings of guanidinoacetate methyltransferase deficiency in an Iranian girl with a homozygous frameshift variant in the GAMT.

Guanidinoacetate methyltransferase deficiency (GAMTD) is a treatable neurodevelopmental disorder with normal or nonspecific imaging findings. Here, we reported a 14-month-old girl with GAMTD and novel findings on brain magnetic resonance imaging (MRI).A 14-||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||month-old female patient was referred to Myelin Disorders Clinic due to onset of seizures and developmental regression following routine vaccination at 4 months of age. Brain MRI, prior to initiation of treatment, showed high signal intensity in T2-weighted imaging in bilateral thalami, globus pallidus, subthalamic nuclei, substantia nigra, dentate nuclei, central tegmental tracts in the brainstem, and posterior periventricular white matter which was masquerading for mitochondrial leukodystrophy. Basic metabolic tests were normal except for low urine creatinine; however, exome sequencing identified a homozygous frameshift deletion variant [NM_000156: c.491del; (p.Gly164AlafsTer14)] in the GAMT. Biallelic pathogenic or likely pathogenic variants cause GAMTD. We confirmed the homozygous state for this variant in the proband, as well as the heterozygote state in the parents by Sanger sequencing.MRI features in GAMTD can mimic mitochondrial leukodystrophy. Pediatric neurologists should be aware of variable MRI findings in GAMTD since they would be misleading to other diagnoses.

High genetic heterogeneity of leukodystrophies in Iranian children: the first report of Iranian Leukodystrophy Registry.

Leukodystrophies (LDs) are a heterogeneous group of progressive neurological disorders and characterized by primary involvement of white matter of the central nervous system (CNS). This is the first report of the Iranian LD Registry database to describe the clinical, radiological, and genomic data of Persian patients with leukodystrophies. From 2016 to 2019, patients suspicious of LDs were examined followed by a brain magnetic resonance imaging (MRI). A single gene testing or whole-exome sequencing (WES) was used depending on the neuroradiologic phenotypes. In a few cases, the diagnosis was made by metabolic studies. Based on the MRI pattern, diagnosed patients were divided into cohorts A (hypomyelinating LDs) versus cohort B (Other LDs). The most recent LD classification was utilized for classification of diagnosed patients. For novel variants, in silico analyses were performed to verify their pathogenicity. Out of 680 registered patients, 342 completed the diagnostic evaluations. In total, 245 patients met a diagnosis which in turn 24.5% were categorized in cohort A and the remaining in cohort B. Genetic tests revealed causal variants in 228 patients consisting of 213 variants in 110 genes with 78 novel variants. WES and single gene testing identified a causal variant in 65.5% and 34.5% cases, respectively. The total diagnostic rate of WES was 60.7%. Lysosomal disorders (27.3%; GM2-gangliosidosis-9.8%, MLD-6.1%, KD-4.5%), amino and organic acid disorders (17.15%; Canavan disease-4.5%, L-2-HGA-3.6%), mitochondrial leukodystrophies (12.6%), ion and water homeostasis disorders (7.3%; MLC-4.5%), peroxisomal disorders (6.5%; X-ALD-3.6%), and myelin protein disorders (3.6%; PMLD-3.6%) were the most commonly diagnosed disorders. Thirty-seven percent of cases had a pathogenic variant in nine genes (ARSA, HEXA, ASPA, MLC1, GALC, GJC2, ABCD1, L2HGDH, GCDH). This study highlights the most common types as well as the genetic heterogeneity of LDs in Iranian children.

Expanding phenotype heterogeneity of NARS2 by presenting subdural hematoma and parenchymal hemorrhage.

BACKGROUND: NARS2 encodes mitochondrial Asparaginyl-tRNA Synthetase 2, which catalyzes the aminoacylation of tRNA-Asn in the mitochondria. To date, 24 variants have been reported in NARS2 gene in 35 patients. The phenotypic variability of NARS2-associated disorder is broad, ranging from neurodevelopmental disorders to hearing loss. In this study, we report some novel imaging findings in an Iranian patient suffering from epileptic encephalopathy, caused by a previously reported variant, c.500A > G; p.(His167Arg), in NARS2. METHODS: The spectrum of clinical manifestations of two Iranian patients was investigated and genetic analysis was performed by Whole-exome sequencing (WES). Additionally, we also reviewed the literature and summarized the phenotypes of previously reported patients with variants in the NARS2 gene. RESULTS: Here, we present the phenotypic and genetic features of 2 unrelated Iranian infants presented with neurodevelopmental delay, seizures, hearing impairment, feeding problems, elevated serum lactate levels in addition to subdural hematoma and cerebral parenchymal hemorrhage in the brain magnetic resonance imaging (MRI) of one of the patients. Genetic analysis revealed a biallelic missense variant in NARS2: c.500A > G; p.(His167Arg). We described the subdural hematoma and cerebral parenchymal hemorrhage of the brain for the first time. CONCLUSIONS: Our study provides new clinical findings, subdural hematoma, and parenchymal hemorrhage, in NARS2-related disorders. Our findings along with previous studies provide more evidence of the clinical presentation of the disease caused by pathogenic variants in NARS2. Expanding the clinical spectrum increases the diagnostic rate of molecular testing and improves the quality of counseling for at-risk couples.

An atypical imaging characteristic of calvarial metastasis of neuroblastoma as multiple multi-loculated cystic masses with internal blood-fluid levels: a case report.

BACKGROUND: As the third most common malignancy of childhood, Neuroblastoma has a great propensity to metastasize to multiple organs. The most common site of metastasis is the bone and bone marrow. Concerning the central nervous system, neuroblastoma usually involves the calvarium and the external dural surface. The skull metastases may show different appearances, including: multiple lytic bone lesions, bone thickening, hair-on-end periosteal reaction, irregular suture widening and/or plaque like epidural deposits. Here we present a case of metastatic neuroblastoma, appearing as multiple multi-loculated cystic epidural masses with internal blood-fluid levels as a rare imaging manifestation of calvarial metastasis. CASE PRESENTATION: An 8-year-old boy with known history of autism, presented to the emergency department with a 3-month history of intermittent fever, malaise and myalgia and headache along with significant weight loss. Laboratory examination revealed elevated ESR and CRP and anemia. On Abdomino-Pelvic imaging a well-defined, 45*30*24 mm, solid-cystic mass was observed, replacing the normal left adrenal gland. On brain MRI, multiple multi-loculated cystic, lentiform masses were observed on the external surface of cerebral hemispheric dura. Multiple fluid-fluid levels were noted in the locules in some of which the dependent fluid was hyperintense on T1w and FLAIR and hypointense on T2w sequences, compatible with blood, representing blood-fluid level. The wall and septa of the masses, enhanced after contrast administration. Associated abnormal marrow signal and aggressive type periosteal reactions were identified in the overlying bone. All of the lesions had increased uptake in MIBG scan. Bone marrow biopsy revealed small round cells, diagnostic for neuroblastoma. The patient underwent chemotherapy treatment. All calvarial/epidural metastatic lesions resolved after chemotherapy and residual adrenal tumor was resected. CONCLUSION: Cystic epidural lesions, especially when associated with adjacent abnormal bone marrow signal, or periosteal reaction and containing blood-fluid level should raise the suspicion of a calvarial metastasis.

The safety and efficacy of umbilical cord blood mononuclear cells in individuals with spastic cerebral palsy: a randomized double-blind sham-controlled clinical trial.

INTRODUCTION: The current multi-center, randomized, double-blind study was conducted among children with cerebral palsy (CP) to assess the safety and efficacy of umbilical cord blood mononuclear cell (UCB-MNC). We performed the diffusion tensor imaging to assess the changes in the white matter structure. METHODS: Males and females aged 4 to 14 years old with spastic CP were included. Eligible participants were allocated in 4:1 ratio to be in the experimental or control groups; respectively. Individuals who were assigned in UCB-MNC group were tested for human leukocyte antigen (HLA) and fully-matched individuals were treated with UCB-MNCs. A single dose (5 × 106 /kg) UCB-MNCs were administered via intrathecal route in experimental group. The changes in gross motor function measure (GMFM)-66 from baseline to one year after treatment were the primary endpoints. The mean changes in modified Ashworth scale (MAS), pediatric evaluation of disability inventory (PEDI), and CP quality of life (CP-QoL) were also evaluated and compared between groups. The mean changes in fractional anisotropy (FA) and mean diffusivity (MD) of corticospinal tract (CST) and posterior thalamic radiation (PTR) were the secondary endpoints. Adverse events were safety endpoint. RESULTS: There were 72 included individuals (36 cases in each group). The mean GMFM-66 scores increased in experimental group; compared to baseline (+ 9.62; 95%CI: 6.75, 12.49) and control arm (ß: 7.10; 95%CI: 2.08, 12.76; Cohen's d: 0.62) and mean MAS reduced in individuals treated with UCB-MNCs compared to the baseline (-0.87; 95%CI: -1.2, -0.54) and control group (ß: -0.58; 95%CI: -1.18, -0.11; Cohen's d: 0.36). The mean PEDI scores and mean CP-QoL scores in two domains were higher in the experimental group compared to the control. The imaging data indicated that mean FA increased and MD decreased in participants of UCB-MNC group indicating improvements in white matter structure. Lower back pain, headaches, and irritability were the most common adverse events within 24 h of treatment that were related to lumbar puncture. No side effects were observed during follow-up. CONCLUSIONS: This trial showed that intrathecal injection of UCB-MNCs were safe and effective in children with CP. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov ( NCT03795974 ).

COVID-19 Pandemic Experiences in Pediatric Intensive Care Unit: An Iranian Referral Hospital-Based Study.

Introduction: In late February 2020, after we had informed about the presence of some cases of COVID-19 in Iran and its rapid spread throughout the country, we decided to make the necessary arrangements for patients with critical conditions in Pediatric Intensive Care Unit (PICU) at Children's Medical Center. There are a little data on critically ill children with COVID-19 infection with ICU requirements. The aim of this study was to describe clinical characteristics, laboratory parameters, treatment, and outcomes of the pediatrics population infected by SARS-CoV-2 admitted to PICU. Materials and Methods: This study was performed between February 2020 and May 2020 in the COVID PICU of the Children's Medical Center Hospital in Tehran, Iran. Patients were evaluated in terms of demographic categories, primary symptoms and signs at presentation, underlying disease, SARS-CoV-2 RT-PCR test result, laboratory findings at PICU admission, chest X-ray (CXR) and lung CT findings, and treatment. Moreover, the need to noninvasive ventilation (NIV) or mechanical ventilation, the length of hospital stay in the PICU, and outcomes were assessed. Results: In total, 99 patients were admitted to COVID PICU, 42.4% (42 patients) were males, and 66 patients had positive SARS-CoV-2 real-time reverse transcriptase-polymerase chain reaction (RT-PCR). There was no statistically significant difference in the frequency of clinical signs and symptoms (except for fever) among patients with positive SARS-CoV-2 RT-PCR and negative ones. Among all admitted patients, the presence of underlying diseases was noticed in 81 (82%) patients. Of 99 patients, 34 patients were treated with NIV during their admission. Furthermore, 35 patients were intubated and treated with mechanical ventilation. Unfortunately, 11 out of 35 mechanically ventilated patients (31%) passed away. Conclusion: No laboratory and radiological findings in children infected with COVID-19 were diagnostic in cases with COVID-19 admitted to PICU. There are higher risks of severe COVID-19, PICU admission, and mortality in children with comorbidities.

Cholecysto-hepatic duct serving as the only drainage pathway of bile from the intrahepatic to the extrahepatic biliary system in an infant: a case report.

BACKGROUND: Cholecystohepatic duct is a rare anomaly of the biliary system which involves drainage of bile into the gallbladder which may be associated with agenesis of the common hepatic duct or common bile duct. CASE PRESENTATION: A 2.5-month-old infant presented to our emergency department with icterus. He had a history of esophageal atresia and imperforate anus which had been treated surgically by thoracotomy, esophagostomy, gastrostomy and colostomy placement. Following imaging studies by ultrasound and MRCP, the diagnosis of common hepatic duct agenesis was made. Cholecystohepatic duct was present as the solitary drainage pathway of bile from the intrahepatic to extrahepatic biliary system. CONCLUSIONS: Cholecystohepatic ducts need a high index of suspicion to be diagnosed on preoperative hepatobiliary imaging. As they may be asymptomatic, they are predisposed to iatrogenic injury during hepatobiliary surgeries.

Symptomatic care of late-onset Alexander disease presenting with area postrema-like syndrome with prednisolone; a case report.

BACKGROUND: Alexander disease (AxD) is classified into AxD type I (infantile) and AxD type II (juvenile and adult form). We aimed to determine the potential genetic cause(s) contributing to the AxD type II manifestations in a 9-year-old male who presented area postrema-like syndrome and his vomiting and weight loss improved after taking prednisolone. CASE PRESENTATION: A normal cognitive 9-year-old boy with persistent nausea, vomiting, and a significant weight loss at the age of 6 years was noticed. He also experienced an episode of status epilepticus with generalized atonic seizures. He showed non-febrile infrequent multifocal motor seizures at the age of 40 days which were treated with phenobarbital. He exhibited normal physical growth and neurologic developmental milestones by the age of six. Occasionally vomiting unrelated to feeding was reported. Upon examination at 9 years, a weak gag reflex, prominent drooling, exaggerated knee-deep tendon reflexes (3+), and nasal tone speech was detected. All gastroenterological, biochemical, and metabolic assessments were normal. Brain magnetic resonance imaging (MRI) revealed bifrontal confluent deep and periventricular white matter signal changes, fine symmetric frontal white matter and bilateral caudate nucleus involvements with garland changes, and a hyperintense tumefactive-like lesion in the brain stem around the floor of the fourth ventricle and area postrema with contrast uptake in post-contrast T1-W images. Latter MRI at the age of 8 years showed enlarged area postrema lesion and bilateral middle cerebellar peduncles and dentate nuclei involvements. Due to clinical and genetic heterogeneities, whole-exome sequencing was performed and the candidate variant was confirmed by Sanger sequencing. A de novo heterozygous mutation, NM_001242376.1:c.262 C > T;R88C in exon 1 of the GFAP (OMIM: 137,780) was verified. Because of persistent vomiting and weight loss of 6.0 kg, prednisolone was prescribed which brought about ceasing vomiting and led to weight gaining of 3.0 kg over the next 3 months after treatment. Occasional attempts to discontinue prednisolone had been resulting in the reappearance of vomiting. CONCLUSIONS: This study broadens the spectrum of symptomatic treatment in leukodystrophies and also shows that R88C mutation may lead to a broad range of phenotypes in AxD type II patients.

Fetal corpus callosum abnormalities: Ultrasound and magnetic resonance imaging role.

The corpus callosum (CC) is the major interhemispheric commissure and its abnormalities include agenesis, hypoplasia, and hyperplasia. The CC anomalies are typically related to other central nervous system (CNS) or extra-CNS malformations. The antenatal diagnosis of complete CC agenesis is easy after mid-trimester by ultrasound (US) even in the axial plane. The non-visualization of cavum septum pellucidum and colpocephaly are critical signs in the axial view. More subtle findings (i.e., hypoplasia and partial agenesis) might also be recognized antenatally. In this review, the focus was given on the prenatal diagnosis of CC abnormalities in US and magnetic resonance imaging.

The clinical significance of biliary findings in magnetic resonance enterography of patients with inflammatory bowel disease.

Purpose: Given the association of inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC), we aimed to investigate the clinical relevance of abnormal hepatobiliary findings on magnetic resonance enterography (MRE) of IBD patients considering the risk of over- or underestimation of PSC at MRE. Material and methods: Using the MRE dataset of patients referring to a tertiary hospital and the National Registry of Crohn's and Colitis, 69 MREs, including 23 IBD-PSC, 23 IBD-without PSC, and 23 healthy controls (HC), were retrospectively reviewed by 2 experienced radiologists blinded to the clinical data, to evaluate hepatobiliary abnormalities. Sensitivity, specificity, and likelihood ratios were calculated. Results: Bile duct irregularities were the most common finding in the IBD-PSC group, with a frequency of 91%. Intra- and extrahepatic bile duct (IHBD and EHBD) irregularities were observed in 87% and 78% of PSC patients, respectively. Higher frequency of IHBD and EHBD wall thickening, bile duct dilation, EHBD stricture, and periportal oedema were observed in the IBD-PSC group. Peribiliary T2-weighted hyperintensities and contrast-enhancement were significantly more common in the IBD-PSC group than in the IBD and HC groups (48% and 35%, respectively) (p < 0.001). Detection of biliary irregularities on MRE had a specificity of 94% (95% CI: 82-99%), a sensitivity of 91% (95% CI: 72-99%), and a positive likelihood ratio of 14.0 (95% CI: 4.7-42.1) for the diagnosis of PSC. Conclusions: This study emphasizes the importance of assessing and reporting hepatobiliary abnormalities visible in the MRE of patients with IBD to avoid a delayed diagnosis of PSC.

Atypical neuroimaging characteristics of hemophagocytic lymphohistiocytosis in infants: a case series of hemorrhagic brain lesions in the deep grey matter.

Hemophagocytic lymphohistiocytosis (HLH) is a rare multisystem condition associated with uncontrolled overproduction and infiltration of lymphocytes and histiocytes predominantly in liver, lymph nodes, spleen, and central nervous system. Neuroimaging findings on MRI are fairly nonspecific and classically include periventricular white matter signal abnormalities and diffuse atrophy. Focal parenchymal lesions may demonstrate post contrast ring or nodular enhancement and calcification. However, the MR imaging characteristics can be highly variable. Here, we present two cases of HLH in infants with multiple hemorrhagic lesions mostly depicted in both thalami and basal ganglia regions. Thalamic, basal ganglia, and brain stem involvement with hemorrhagic changes in HLH are rarely described in literature. Early diagnosis of HLH may be lifesaving. Awareness of the disease is necessary to investigate its characteristic findings and avoiding a delay in diagnosis.

Fruits and vegetables intake and its subgroups are related to depression: a cross-sectional study from a developing country.

BACKGROUND: The association of fruits and vegetables (FV) specific subgroups consumption and depression has not been investigated in healthy adult populations. Therefore, the aim of our study was to determine the relationship between intake of FV as well as their subgroups and depression. METHODS: This cross-sectional study was conducted on 400 women attending healthcare centers. The scores of depression, anxiety, and stress were measured using the 21-item depression, anxiety and stress scales questionnaire. The participants' anthropometric and physical activity data were collected and the 147-item semi-quantitative FFQ was used for estimating the FV intake. RESULTS: After adjustment for confounding variables, the participants in the lower quartiles of total FV, total vegetables, total fruits, citrus, other fruits and green leafy vegetables intake were more likely to experience depression compared to those in the higher quartiles (p trend < 0.03). CONCLUSION: Our findings suggest that higher intake of total FV and some of its specific subgroups might be associated with depression.

Semi-automatic Methods for Airway and Adjacent Vessel Measurement in Bronchiectasis Patterns in Lung HRCT Images of Cystic Fibrosis Patients.

Airway and vessel characterization of bronchiectasis patterns in lung high-resolution computed tomography (HRCT) images of cystic fibrosis (CF) patients is very important to compute the score of disease severity. We propose a hybrid and evolutionary optimized threshold and model-based method for characterization of airway and vessel in lung HRCT images of CF patients. First, the initial model of airway and vessel is obtained using the enhanced threshold-based method. Then, the model is fitted to the actual image by optimizing its parameters using particle swarm optimization (PSO) evolutionary algorithm. The experimental results demonstrated the outperformance of the proposed method over its counterpart in R-squared, mean and variance of error, and run time. Moreover, the proposed method outperformed its counterpart for airway inner diameter/vessel diameter (AID/VD) and airway wall thickness/vessel diameter (AWT/VD) biomarkers in R-squared and slope of regression analysis.

Depression is related to dietary diversity score in women: a cross-sectional study from a developing country.

BACKGROUND: Substantial evidence provides support for the role of diet in the prevention and control of mental disorders. However, since there is no study regarding the relationship between dietary diversity and stress or depression, we aimed to determine the relationship between the dietary diversity score (DDS) and stress and depression in women. METHODS: This descriptive-analytical cross-sectional study was performed on 360 women aged 20-49 years attending health centers in the south of Tehran. The dietary intake and score of depression, anxiety, and stress were measured using a 24-h dietary recall and the 42-item depression, anxiety, stress scales questionnaire, respectively. The DDS was calculated based on the FAO 2013 guidelines. Data were analyzed using Chi-square, analysis of variance, Spearman correlation coefficient, and multivariable logistic regression tests. RESULTS: In total, 31.4 and 25.8% of the subjects suffered from depression and stress, respectively. After adjusting for confounders, a one-unit increase in DDS was associated with a 39% reduction in the risk of severe depression. The DDS was not significantly associated with mild or moderate depression, and no significant relationship was observed between the DDS and stress. CONCLUSIONS: The DDS could be inversely associated with depression in women. Since we observed no significant relationship between stress and DDS, further studies are needed in this regard.

Defining the surface anatomy of the central venous system in children.

Pediatric emergency physicians, pediatric critical care specialists, and pediatric surgeons perform central venous catheterization in many clinical settings. Complications of the procedure are not uncommon and can be fatal. Despite the frequency of application, the evidence-base describing the surface landmarks involved is missing. The aim of the current study was to critically investigate the surface markings of the central venous system in children. The superior vena cava/right atrial (SVC/RA) junction, superior vena cava (SVC) formation, and brachiocephalic vein (BCV) formation were examined independently by two investigators. Three hundred computed tomography (CT) scans collected across multiple centers were categorized by age group into: 0-3 years, 4-7 years, and 8-11 years. Scans with pathology that distorted or obscured the regional anatomy were excluded. The BCV formation was commonly found behind the ipsilateral medial clavicular head throughout childhood. This contrasts with the variable levels of SVC formation, SVC length, and SVC/RA junction. In the youngest group, SVC formation was most commonly at the second costal cartilage (CC), but moved to the first CC/first intercostal space (ICS) as the child grew. The SVC/RA junction was at the fourth CC in the youngest group and moved to the third CC/third ICS as the child grew. This study demonstrates the variable anatomy of SVC formation and the SVC/RA junction with respect to rib level. This variability underscores the unreliability of surface anatomical landmarks of the SVC/RA junction as a guide to catheter tip position.

A reappraisal of adult thoracic and abdominal surface anatomy in Iranians in vivo using computed tomography.

Surface anatomy is a core component of human anatomy in clinical practice. It allows clinicians to assess patients accurately and quickly; however, recent studies have revealed variability among individuals and ethnicities. The aim of this study is to investigate possible variations in adult thoracic and abdominal surface anatomy landmarks in an Iranian population. This study used 100 thoracoabdominal CT scans (mean age: 47 ± 17 years, age range: 20-77 years, 47% females), noted the most common locations of clinically relevant surface markings, and analyzed correlations between these variables and age or gender. While many common surface markings in Iranians were consistent with the evidence-based literature, there were some differences. In relation to the corresponding segments of the vertebral column, the superior vena cava formation and the lower border of the pleura adjacent to the vertebral column and right kidney tended to be at higher levels in adult Iranians than a Caucasian population. There were also discrepancies between the Iranian population and commonly-referenced medical textbooks and recent evidence-based literature concerning the vertebral levels of the diaphragmatic openings of the esophagus, aorta, and inferior vena cava. This study emphasizes the need to consider evidence-based reappraisals of surface anatomy to guide clinical practice. Much of our current knowledge of surface anatomy is based on older studies of cadavers rather than living people, and does not take ethnic and individual variations into consideration.

Radiologic resolution of malignant infantile osteopetrosis skeletal changes following hematopoietic stem cell transplantation.

INTRODUCTION: Hematopoietic stem cell transplantation (HSCT) is the only known curative treatment of malignant infantile osteopetrosis (MIOP). In this study, short-term serial bone surveys were used to assess radiologic evolution of skeletal changes after HSCT in MIOP. MATERIALS AND METHODS: Baseline whole-body bone survey was performed in all patients. HSCT was successful in 14 patients (11 with full chimerism, three with mixed chimerism) in whom follow-up bone surveys were carried out at 6 and 12 months after HSCT. RESULTS: Normal corticomedullary differentiation was evident in five (P = 0.06) and 12 (P < 0.005) patients at 6 and 12 months, respectively. Abnormal endobone appearance in long bones, present in 11 participants at baseline exam, disappeared in eight (P = 0.008) and all (P = 0.001) patients at 6 and 12 months, respectively. In 6-month follow-up, rachitic changes significantly disappeared (P < 0.01) in long bones; however, they were evident in ribs of 12 patients (P = 0.50). No patient had rickets in ribs or long bones after 12 months. CONCLUSION: We observed considerable resolution of MIOP skeletal changes after HSCT in all patients with either full or mixed chimerism. Rachitic changes in long bones, attenuated corticomedullary differentiation, and endobone appearance were the first to resolve. We propose using single long bone plain x-ray to demonstrate short-term skeletal response to HSCT.

Pediatric Inflammatory Myofibroblastic Tumor of Rectosigmoid Junction: A Case Report and Review of the Literature.

The occurrence of rectosigmoid junction inflammatory myofibroblastic tumor (IMT) is uncommon in children. This is a rare form of mesenchymal tumor, belonging to the category of soft tissue tumors, and can be found at any anatomical site from the central nervous system to the gastrointestinal tract. Our patient was a 10-year-old male subject complaining of lack of defecation and constipation. The patient had decreased the frequency of defecation and constipation about two weeks before his referral and had not improved despite the use of laxatives. The abdomen was completely distended and there was no tenderness or guarding in the examination. Several airfluid levels are shown on the abdominal X-ray. In the ultrasound, free fluid was reported in the interlobular and pelvic spaces. The patient was transferred into the operating room. A tumor of the rectosigmoid junction was detected. Histopathologic studies showed evidence of IMT. IMT is a rare neoplasm of unknown origin, which may occur in various sites of the body. Complete surgical removal is usually curative, but early detection of recurrence is required. Treatment options include chemotherapy, radiation therapy, and immunotherapy. Further investigations are needed to improve the understanding and management of this rare tumor.

A comprehensive study of mutation and phenotypic heterogeneity of childhood mitochondrial leukodystrophies.

OBJECTIVE: Mitochondrial leukodystrophies (MLs) are mainly caused by impairments of the mitochondrial respiratory chains. This study reports the mutation and phenotypic spectrum of a cohort of 41 pediatric patients from 39 distinct families with MLs among 320 patients with a molecular diagnosis of leukodystrophies. METHODS: This study summarizes the clinical, imaging, and molecular data of these patients for five years. RESULTS: The three most common symptoms were neurologic regression (58.5%), pyramidal signs (58.5%), and extrapyramidal signs (43.9%). Because nuclear DNA mutations are responsible for a high percentage of pediatric MLs, whole exome sequencing was performed on all patients. In total, 39 homozygous variants were detected. Additionally, two previously reported mtDNA variants were identified with different levels of heteroplasmy in two patients. Among 41 mutant alleles, 33 (80.4%) were missense, 4 (9.8%) were frameshift (including 3 deletions and one duplication), and 4 (9.8%) were splicing mutations. Oxidative phosphorylation in 27 cases (65.8%) and mtDNA maintenance pathways in 8 patients (19.5%) were the most commonly affected mitochondrial pathways. In total, 5 novel variants in PDSS1, NDUFB9, FXBL4, SURF1, and NDUSF1 were also detected. In silico analyses showed how each novel variant may contribute to ML pathogenesis. CONCLUSIONS: The findings of this study suggest whole-exome sequencing as a strong diagnostic genetic tool to identify the causative variants in pediatric MLs. In comparison between oxidative phosphorylation (OXPHOS) and mtDNA maintenance groups, brain stem and periaqueductal gray matter (PAGM) involvement were more commonly seen in OXPHOS group (P value of 0.002 and 0.009, respectively), and thinning of corpus callosum was observed more frequently in mtDNA maintenance group (P value of 0.042).