A female case of L1 syndrome that may have developed due to skewed X inactivation.

BACKGROUND: Heterozygous L1CAM variants cause L1 syndrome with hydrocephalus and aplasia/hypoplasia of the corpus callosum. L1 syndrome usually has an X-linked recessive inheritance pattern; however, we report a rare case occurring in a female child. CASE PRESENTATION: The patient's family history was unremarkable. Fetal ultrasonography revealed enlarged bilateral ventricles of the brain and hypoplasia of the corpus callosum. The patient was born at 38 weeks and 4 days of gestation. Brain MRI performed on the 8th day of life revealed enlargement of the brain ventricles, marked in the lateral and third ventricles with irregular margins, and hypoplasia of the corpus callosum. Exome sequencing at the age of 2 years and 3 months revealed a de novo heterozygous L1CAM variant (NM_000425.5: c.2934_2935delp. (His978Glnfs * 25). X-chromosome inactivation using the human androgen receptor assay revealed that the pattern of X-chromosome inactivation in the patients was highly skewed (96.6 %). The patient is now 4 years and 11 months old and has a mild developmental delay (developmental quotient, 56) without significant progression of hydrocephalus. CONCLUSION: In this case, we hypothesized that the dominant expression of the variant allele arising from skewed X inactivation likely caused L1 syndrome. Symptomatic female carriers may challenge the current policies of prenatal and preimplantation diagnoses.

A case of epilepsy with myoclonic atonic seizures caused by SLC6A1 gene mutation due to balanced chromosomal translocation.

INTRODUCTION: Epilepsy with myoclonic atonic seizures (EMAtS) was previously thought to occur in normally developing children. We report a female case of EMAtS and mild developmental delay before onset. Importantly, a de novo balanced chromosomal translocation was recognized in the patient. CASE PRESENTATION: The patient was a 4-year-old girl. Mild developmental delay was observed during infancy. At the age of one and a half years, she developed atonic seizures once a month. At 4 years of age, her seizures increased to more than 10 times per hour. An ictal electroencephalogram (EEG) showed a 3-4-Hz spike-and-wave complex, which was consistent with atonic and myoclonic seizures of the trunk, eyelids, and lips. Therefore, EMAtS was diagnosed based on the symptoms and EEG findings. After administration of valproic acid (VPA), the epileptic seizures disappeared immediately. At the age of 5 years and 2 months, the seizures recurred but disappeared again when the dose of VPA was increased. Subsequently, no recurrence was observed until 6 years and 3 months of age on VPA and lamotrigine. Chromosome analysis of the patient disclosed 46,XX,t(3;11)(p25;q13.1)dn. Long-read sequencing of the the patient's genomic DNA revealed that the 3p25.3 translocation breakpoint disrupted the intron 7 of the SLC6A1 gene. CONCLUSION: The SLC6A1 disruption by chromosome translocation well explains the clinical features of this patient. Long-read sequencing is a powerful technique to determine genomic abnormality at the nucleotide level for disease-associated chromosomal abnormality.

Brain abnormalities in children with attention-deficit/hyperactivity disorder assessed by multi-delay arterial spin labeling perfusion and voxel-based morphometry.

PURPOSE: To obtain an understanding of the correlation between hemodynamic differences and morphological changes as well as potential sex differences in children with ADHD using multi-delay pseudo-continuous arterial spin labeling (pCASL) imaging and voxel-based morphometry (VBM), especially given that previous findings are limited for girls. MATERIALS AND METHODS: We recruited 23 children with ADHD (mean age, 8.3 years; 19 boys; 4 girls) and 24 children without ADHD (mean age, 9.1 years; 13 boys; 11 girls) as controls. All participants underwent 3D multi-delay pCASL and T1-weighted imaging. The voxel-based statistical parameter mapping (SPM) method was used for group-wise comparisons. RESULTS: Compared with controls, children with ADHD exhibited decreased regional cerebral blood flow (rCBF) and gray matter volume (GMV) in the left middle frontal gyrus and left postcentral gyrus. Analysis by sex revealed reduced rCBF and GMV in the left lingual gyrus and left inferior occipital gyrus in boys with ADHD versus controls and increased rCBF and GMV in the left superior frontal gyrus in girls with ADHD. CONCLUSION: Although our results are preliminary because of small sample sizes, several brain regions exhibit changes in both cerebral perfusion and GMV in the same direction in patients with ADHD, with boys with ADHD showing decreased activity and girls with ADHD displaying increased activity in the fronto-parietal cortices.

Advanced Abdominal Pregnancy (AAP) after 20 Weeks of Gestation in Japan: A Retrospective Review.

BACKGROUND: An advanced abdominal pregnancy (AAP) rarely continues to a live birth, but sometimes, a live birth may occur. In developed countries, women with AAP who have not been diagnosed preoperatively are expected to be diagnosed quickly, and the pregnant woman and the fetus will be saved. After careful examination of the past cases, we sought to derive what is the best diagnosis and treatment choice in the current medical environment. MATERIALS AND METHODS: We retrospectively studied AAP cases in Japan. We examined diagnosis of AAP before fetal delivery and placental treatment at the time of delivery. AAP was well documented in 10 cases. We contacted the AAP authors, who reported 10 AAP cases in Japan, directly to confirm any unclear points. RESULTS: Two cases were diagnosed with AAP before laparotomy, one was diagnosed after IUFD, and seven were diagnosed at the time of laparotomy. The two most recent cases were diagnosed with AAP preoperatively by ultrasound and MRI. Six cases were described for preoperative diagnosis. There were two cases of placenta previa, one of a bicornuate uterus, one of breech presentation, one of a combination of uterine cervical fibroids and placenta previa, and one of a combination of presentation and placental abnormality with uterine fibroids. In five cases, the placenta was removed at the time of laparotomy. Simultaneous removal of the placenta during laparotomy could not be performed because of intra-amniotic infection with a macerated fetus in an IUFD case. Among eight cases, excluding 20-week and 21-week gestation with no expectation of viable newborns, there were one male and seven female fetuses. The birth weight ranged from 1765 to 3520 g, with a median birth weight of 2241 g. Combined malformations were described in six of the seven live births. Clubfoot, torticollis, joint contracture, and bone deformity were transient because intrauterine compression quickly improved. CONCLUSION: In recent cases, AAP has been diagnosed by MRI and ultrasound. MRI should be performed if abdominal pregnancy is suspected. Postoperative infections may occur if the placenta is not removed at the time of delivery. We recommend placental resection with the help of an anesthesiologist, a gynecologist, a urologist, and a surgeon in the current medical environment.

Usefulness of Near-Infrared Spectroscopy (NIRS) for evaluating drug effects and improvements in medication adherence in children with Attention Deficit Hyperactivity Disorder (ADHD).

The symptoms of attention deficit hyperactivity disorder (ADHD) are inattention, hyperactivity, and impulsiveness. Physicians often prescribe methylphenidate (MPH) for children with ADHD for long periods of time. The purpose of the present study was to investigate the usefulness of near-infrared spectroscopy (NIRS) for evaluating drug effects and improvements in medication adherence in children with ADHD. Subjects were 10 male children diagnosed with ADHD : average age, 9.3 years, and 10 boys with typical development : average age 9.5 years. Children with intellectual disability, autism, and obvious depressive symptoms were excluded. The present study revealed that in the ADHD group, oxy-Hb concentrations in the left and right lateral prefrontal cortex significantly increased during the execution of the Stroop color-word test in both channels when taking MPH. This method was considered to be useful for assessing drug effects on ADHD because NIRS is an objective indicator for evaluating ADHD executive dysfunction and visualizes the activation of frontal lobe function by MPH. A pediatric neurologist explained the results of NIRS while presenting images to the ADHD group, and medication adherence and the drug-taking ratio both markedly improved. Therefore, this therapeutic explanation is an effective strategy for improving medication compliance and adherence among patients. J. Med. Invest. 68 : 53--58, February, 2021.

Next-generation sequencing for the diagnosis of patients with congenital multiple anomalies and†/†or intellectual disabilities.

Background : In clinical practice, a large proportion of patients with multiple congenital anomalies and/or intellectual disabilities (MCA / ID) lacks a specific diagnosis. Recently, next-generation sequencing (NGS) has become an efficient strategy for genetic diagnosis of patients with MCA/ID. OBJECTIVE: To review the utility of NGS for the diagnosis of patients with MCA / ID. METHOD: Patients with MCA/ID were recruited between 2013 and 2017. Molecular diagnosis was performed using NGS-based targeted panel sequencing for 4,813 genes. Promising causative variants underwent confirmation by Sanger sequencing or chromosomal microarray. RESULTS: Eighteen patients with MCA/ID were enrolled in this study. Of them, 8 cases (44%) were diagnosed by targeted panel sequencing. Most of diagnosed patients were able to receive better counseling and more appropriate medical management. CONCLUSION: NGS-based targeted panel sequencing seems to be an effective testing strategy for diagnosis of patients with MCA/ID. J. Med. Invest. 67 : 246-249, August, 2020.

Bucillamine-induced gigantomastia with galactorrhea and hyperprolactinaemia.

Gigantomastia is characterised by excessive breast growth and can occur as a rare, drug-induced adverse event. D-penicillamine is the most frequent cause of drug-induced gigantomastia. Only one case of gigantomastia due to bucillamine, an analogue of D-penicillamine, has been reported so far. We herein report a case of bucillamine-induced gigantomastia presenting with acute enlargement of the bilateral breasts and accessory breast tissue in the axillae 7 months after the start of bucillamine therapy. Awareness about this rare adverse event is important since bucillamine is still widely used in Japan and Korea.

Synergistic Effect of Additive and Solvent Vapor Annealing on the Enhancement of MAPbI3 Perovskite Solar Cells Fabricated in Ambient Air.

To date, most high-performance perovskite solar cells (PSCs) are fabricated in an inert or vacuum condition to circumvent the moisture effect, which is one of the leading causes of sparse crystal nucleation and nonuniform morphology. Therefore, it is crucial to develop a simple approach to deposit a uniform and homogeneous perovskite on a planar substrate in ambient air for the mass production of PSCs. Herein, we investigated the synergistic effect of additive 1,8-diiodooctane (DIO) and solvent vapor annealing (SVA) treatments on the performance of PSCs fabricated in ambient air. It was found that the addition of 1 vol % DIO together with SVA treatment results in the enhancement of the perovskite film's crystallinity, grain size, and photophysical properties. PSCs containing 1 vol % DIO additive and SVA treatment exhibited a power conversion of efficiency (PCE) of 17.04%, which is markedly higher than the control device with a PCE of 10.61%. The results indicate that the additive DIO and SVA can work together to significantly improve the performance of PSCs fabricated in ambient air. This work provides a promising route for developing high-performance PSCs in the ambient environment.

Molecular diagnosis of an infant with TSC2/PKD1 contiguous gene syndrome.

A 1-month-old Japanese infant with cardiac rhabdomyoma was diagnosed with TSC2/PKD1 contiguous gene syndrome by targeted panel sequencing with subsequent quantitative polymerase chain reaction that revealed gross monoallelic deletion, including parts of two genes: exons 19-42 of TSC2 and exons 2-46 of PKD1. Early molecular diagnosis can help to detect bilateral renal cyst formation and multidisciplinary follow-up of this multisystem disease.

Survey of patients with spinal muscular atrophy on the island of Shikoku, Japan.

BACKGROUND: Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder associated with spinal motor neuron loss and characterized by generalized muscle weakness. Only a few reports exist on SMA epidemiology in Japan. Additionally, nusinersen recently became available as a treatment for this condition. We estimated the prevalence of each type of SMA on Shikoku, Japan's fourth-largest major island. METHODS: We sent a questionnaire to all 131 hospitals in Shikoku that have pediatrics or neurology departments from March to September 2019, asking whether each hospital had SMA patients at that time. If so, we sent a second questionnaire to obtain more detailed information on the clinical data and treatment of each patient. RESULTS: A total of 117 hospitals (89.3%) responded to our first questionnaire, and 21 SMA patients were reported, 16 of whom had homozygous deletion of SMN1. Of the 21, nine had SMA type 1, five were type 2, five were type 3, one was type 4, and one was unidentified. The estimated prevalence for all instances of SMA and 5q-SMA was 0.56 and 0.43 per 100,000 people, respectively. Thirteen patients had received nusinersen therapy. Its outcomes varied from no obvious effects and being unable to sit to being able to sit independently. CONCLUSION: Our data showed the prevalence of SMA types 2 and 3 was relatively low on Shikoku compared with previous reports from other countries, suggesting delayed diagnosis may affect the results. Remaining motor function may be one predicting factor. Greater awareness of SMA among clinicians and patients seems necessary for more accurate epidemiological studies.

Association of Dermatomyositis Sine Dermatitis With Anti-Nuclear Matrix Protein 2 Autoantibodies.

Importance: Reports on dermatomyositis (DM) sine dermatitis (DMSD) are scarce, and the concept of the disease has not been widely accepted. Objective: To confirm the existence of DMSD, determine its prevalence, and characterize its serologic features. Design, Setting, and Participants: This is a cohort study that reviewed clinical information, laboratory data, and muscle pathology slides from January 2009 to August 2019. We further assessed the follow-up data of 14 patients with DMSD. The median (interquartile range) follow-up period was 34 (16-64) months. Muscle biopsy samples, along with clinical information and laboratory data, were sent to a referral center for muscle diseases in Japan for diagnosis. Of patients whose myopathologic diagnosis was made at the National Center of Neurology and Psychiatry between January 2009 and August 2019, 199 patients were eligible for inclusion. These patients underwent full investigation for DM-specific autoantibodies (against transcriptional intermediary factor γ, Mi-2, melanoma differentiation-associated gene 5, nuclear matrix protein 2 [NXP-2], and small ubiquitin-like modifier activating enzyme ); however, 17 patients were excluded because their muscle fibers did not express myxovirus resistance protein A, a sensitive and specific marker of DM muscle pathology. Main Outcomes and Measures: Diagnosis of DMSD was based on the absence of a skin rash at the time of muscle biopsy. Results: Of the 182 patients, 93 were women (51%) and 46 were children (25%) (<18 years). Fourteen patients (8%) had DMSD and none were clinically diagnosed with DM. Among the 14 patients with DMSD, 12 (86%) were positive for anti-NXP-2 autoantibodies, while the remaining 2 were positive for anti-transcriptional intermediary factor γ and anti-Mi-2 autoantibodies, respectively. Only 28% of patients (47 of 168) with a skin rash were positive for anti-NXP-2 autoantibodies, indicating a significant association between anti-NXP-2 autoantibodies and DMSD (86% [12 of 14] vs 28% [47 of 168]; P < .001). This association was also supported by multivariable models adjusted for disease duration (odds ratio, 126.47; 95% CI, 11.42-1400.64; P < .001). Conclusions and Relevance: Dermatomyositis sine dermatitis does exist and accounts for 8% of patients with DM confirmed with muscle biopsy. Dermatomyositis sine dermatitis is significantly associated with anti-NXP-2 autoantibodies, which contrasts with anti-MDA5 DM, which is typically clinically amyopathic in presentation. It is essential to distinguish DMSD from other types of myositis because DM-specific therapies that are currently under development, including Janus kinase inhibitors, may be effective for DMSD.

Improvement of epilepsy with lacosamide in a patient with ring chromosome 20 syndrome.

BACKGROUND: Ring chromosome 20 syndrome is a rare chromosomal disorder characterized by refractory seizure, mental retardation, and behavioral problems. Although there are reports of the effective treatment of patients with antiepileptic drugs (AEDs), no study has reported the effects of lacosamide(LCM) in children with this syndrome. We report a 7-year-old boy with this syndrome whose refractory and behavioral abnormalities have been remarkably improved by treatment with LCM. CASE PRESENTATION: The patient was a 7-year-old boy with no medical or family history of epilepsy. He developed epilepsy with cessation of movement and derivation of the eyes followed by hyperkinetic seizures that made him squeak strangely and cling to his parents. The seizures lasted for less than a minute and were frequent (they occurred more than 30 times a day), particularly at night. Behavioral abnormalities such as hyperactivity also presented. Brain magnetic resonance imaging revealed no structural abnormalities, but an interictal electroencephalogram (EEG) indicated spikes and waves in the frontal lobe dominantly, and ictal single-photon emission computed tomography (SPECT) revealed a blood flow increase in the bilateral orbital frontal area in comparison to interictal SPECT. After chromosome examination, we diagnosed the patient with ring chromosome 20 syndrome (4/30 mosaic). Carbamazepine was ineffective, and seizures were exacerbated with levetiracetam (LEV). LCM was added to the treatment regimen with valproic acid (VPA) and lamotrigine (LTG); consequently, the seizures disappeared, and EEG results also improved. The patient's behavioral disorders, such as hyperactivity, were improved, and he was able to return to elementary school. CONCLUSION: Although VPA and LTG are generally effective for the treatment of ring chromosome 20 syndrome, they do not completely suppress seizures. LCM can be considered an effective option for seizure control in patients with this syndrome.

Multi-delay arterial spin labeling brain magnetic resonance imaging study for pediatric autism.

INTRODUCTION: Arterial spin labeling (ASL) is a non-invasive magnetic resonance imaging (MRI) technique that can measure regional cerebral blood flow (rCBF) without radiation exposure. This study aimed to evaluate rCBF in individuals with autism and their age-matched controls, globally and regionally. METHODS: We performed ASL MRI (3 T, pulsed-continuous ASL, 3 delayed ASL imaging sequences) for 33 patients with autism spectrum disorder (ASD) (average age: 7.3 years, range: 2-14 years). Nineteen children (average age: 8.6 years, range: 3-15 years) without ASD and intellectual delay were included as controls. Patients with morphological abnormalities detected on MRI were excluded. Objective analysis was performed with automatic region of interest analysis of the ASL results. The Mann-Whitney U test was used to compare the rCBF results between the groups. RESULTS: Compared to the controls, patients with ASD showed a statistically significant decrease in rCBF, respectively, in the insula [left, rCBF 51.8 ±â€¯9.5 mL/100 g/min (mean ±â€¯SD) versus 59.9 ±â€¯9.8, p = 0.0017; right, 51.2 ±â€¯10.1 versus 57.8 ±â€¯8.8, p = 0.0354], superior parietal lobule (left, 44.6 ±â€¯8.4 versus 52.0 ±â€¯7.8, p = 0.003), superior temporal gyrus (left, 50.0 ±â€¯8.6 versus 56.9 ±â€¯8.6, p = 0.007; right, 49.5 ±â€¯8.4 versus 56.4 ±â€¯7.7, p = 0.0058), and inferior frontal gyrus (left, 53.0 ±â€¯9.8 versus 59.3 ±â€¯9.9, p = 0.0279), which are associated with the mirror neuron system. CONCLUSIONS: We concluded that patients with ASD showed a statistically significant decline in CBF in regions associated with the mirror neuron system. The advantages of ASL MRI include low invasiveness (no radiation exposure) and short imaging time (approximately 5 min). Studies with larger sample sizes are required to establish the diagnostic value of ASL MRI for ASD.

Multiple atypical thymic carcinoids with paraneoplastic giant cell arteritis.

Multiple thymic carcinoids are rare, and giant cell arteritis (GCA) is one of the less recognized paraneoplastic diseases. The co-occurrence of these two diseases is therefore extremely rare. We report herein a patient with multiple atypical thymic carcinoids and asymptomatic paraneoplastic GCA. All the thymic carcinoids were diagnosed histopathologically as atypical thymic carcinoids with an intrathymic metastasis. Treatment consisted of a complete tumor resection followed by observation of the GCA without any adjuvant therapy. Subsequent positron emission tomography revealed a decrease in F-fludeoxyglucose accumulation in the systemic arteries. Based on these findings, paraneoplastic GCA was diagnosed. Thymic carcinoids rarely involve intrathymic metastasis or cause neopleonastic GCA. However, when they do, a complete tumor resection is the best option for management.

A 16q22.2-q23.1 deletion identified in a male infant with West syndrome.

In partial monosomy of the distal part of chromosome 16q, abnormal facial features, intellectual disability (ID), and feeding dysfunction are often reported. However, seizures are not typical and the majority of them were seizure-free. Here we present the case of a 16q22.2-q23.1 interstitial deletion identified in a male patient with severe ID, facial anomalies including forehead protrusions and flat nose bridge, patent ductus arteriosus, bilateral vocal cord atresia treated by tracheotomy, and West syndrome, which were developed 10 months after birth. Although phenobarbital, sodium valproate (VPA), and zonisamide were not effective as monotherapies or combination therapies, the patient's epileptic seizures and electroencephalogram anomalies disappeared following combined therapy with lamotrigine and VPA. Although WW Domain Containing Oxidoreductase (WWOX), which is known as a cause of autosomal recessive epileptic encephalopathy, was included within the 6.8-Mb deleted region which identified by targeted panel sequencing and validated by chromosomal microarray analysis, no pathogenic variants were detected in the other allele of WWOX. Therefore, it is possible that other genes within or outside of the long deleted region or their interactions may cause West syndrome in this patient.

Photoelectric Properties of OLEDs With and Without Fluorinated Self-Assembled Monolayer and by Varying Thickness of α-NPD.

In this study, we investigated the photoelectric effect and optimization of an organic light-emitting diode (OLED) depending on the presence or absence of a fluorinated self-assembled monolayer (FLSAM) and by varying the thickness of N,N'-Di (1-naphthyl)-N,N'-diphenyl-(1,1'-biphenyl)-4,4'-diamine (α-NPD) from 0 nm to 50 nm. The large distinction in electronegativity between the carbon and the fluorine replacing hydrogen in the alkyl chain of FLSAM generates a strong dipole moment to elevate the vacuum level, resulting in a change of the work function. This eliminates the injection barrier between the work function of the ITO modified by FLSAM and the highest occupied molecular orbital (HOMO) level of the hole-transport layer, thus leading to excellent driving voltage characteristics. Devices without FLSAM had a driving voltage more than twice that of devices using with FLSAM. The introduction of α-NPD as the hole-transport layer enhanced the electrical conductivity by facilitating the transport of holes. However, due to the inherent insulating film properties of α-NPD, the increase in its thickness resulted in a decrease in current density.

A rare male patient with classic Rett syndrome caused by MeCP2_e1 mutation.

Rett syndrome (RTT) is a severe neurodevelopmental disorder typically affecting females. It is mainly caused by loss-of-function mutations that affect the coding sequence of exon 3 or 4 of methyl-CpG-binding protein 2 (MECP2). Severe neonatal encephalopathy resulting in death before the age of 2 years is the most common phenotype observed in males affected by a pathogenic MECP2 variant. Mutations in MECP2 exon 1 affecting the MeCP2_e1 isoform are relatively rare causes of RTT in females, and only one case of a male patient with MECP2-related severe neonatal encephalopathy caused by a mutation in MECP2 exon 1 has been reported. This is the first reported case of a male with classic RTT caused by a 5-bp duplication in the open-reading frame of MECP2 exon 1 (NM_001110792.1:c.23_27dup) that introduced a premature stop codon [p.(Ser10Argfs*36)] in the MeCP2_e1 isoform, which has been reported in one female patient with classic RTT. Therefore, both males and females displaying at least some type of MeCP2_e1 mutation may exhibit the classic RTT phenotype.

A Proton Magnetic Resonance Spectroscopic Study in Autism Spectrum Disorder Using a 3-Tesla Clinical Magnetic Resonance Imaging (MRI) System: The Anterior Cingulate Cortex and the Left Cerebellum.

The pathophysiology of autism spectrum disorder (ASD) is not fully understood. We used proton magnetic resonance spectroscopy to investigate metabolite concentration ratios in the anterior cingulate cortex and left cerebellum in ASD. In the ACC and left cerebellum studies, the ASD group and intelligence quotient- and age-matched control group consisted of 112 and 114 subjects and 65 and 45 subjects, respectively. In the ASD group, γ-aminobutyric acid (GABA)+/ creatine/phosphocreatine (Cr) was significantly decreased in the anterior cingulate cortex, and glutamate (Glu)/Cr was significantly increased and GABA+/Cr was significantly decreased in the left cerebellum compared to those in the control group. In addition, both groups showed negative correlations between Glu/Cr and GABA+/Cr in the left cerebellum, and positive correlations between GABA+/Cr in the anterior cingulate cortex and left cerebellum. ASD subjects have hypoGABAergic alterations in the anterior cingulate cortex and hyperglutamatergic/hypoGABAergic alterations in the left cerebellum.

Assessment of Anterior Cingulate Cortex (ACC) and Left Cerebellar Metabolism in Asperger's Syndrome with Proton Magnetic Resonance Spectroscopy (MRS).

PURPOSE: Proton magnetic resonance spectroscopy (1H MRS) is a noninvasive neuroimaging method to quantify biochemical metabolites in vivo and it can serve as a powerful tool to monitor neurobiochemical profiles in the brain. Asperger's syndrome (AS) is a type of autism spectrum disorder, which is characterized by impaired social skills and restrictive, repetitive patterns of interest and activities, while intellectual levels and language skills are relatively preserved. Despite clinical aspects have been well-characterized, neurometabolic profiling in the brain of AS remains to be clear. The present study used proton magnetic resonance spectroscopy (1H MRS) to investigate whether pediatric AS is associated with measurable neurometabolic abnormalities that can contribute new information on the neurobiological underpinnings of the disorder. METHODS: Study participants consisted of 34 children with AS (2-12 years old; mean age 5.2 (±2.0); 28 boys) and 19 typically developed children (2-11 years old; mean age 5.6 (±2.6); 12 boys) who served as the normal control group. The 1H MRS data were obtained from two regions of interest: the anterior cingulate cortex (ACC) and left cerebellum. RESULTS: In the ACC, levels of N-acetylaspartate (NAA), total creatine (tCr), total choline-containing compounds (tCho) and myo-Inositol (mI) were significantly decreased in children with AS compared to controls. On the other hand, no significant group differences in any of the metabolites were found in the left cerebellum. Neither age nor sex accounted for the metabolic findings in the regions. CONCLUSION: The finding of decreased levels of NAA, tCr, tCho, and mI in the ACC but not in left cerebellar voxels in the AS, suggests a lower ACC neuronal density in the present AS cohort compared to controls.

A case of early onset epileptic encephalopathy with de novo mutation in SLC35A2: Clinical features and treatment for epilepsy.

INTRODUCTION: Mutations of SLC35A2 that encodes Golgi-localized Uridine diphosphate (UDP)-galactose transporter at Xp11.23 lead to congenital disorders of glycosylation (CDG). Although patients with CDG generally have diverse systemic symptoms, patients with a SLC35A2 mutation manifest predominantly disorders of the central nervous system (CNS). CASE REPORT: A female infant aged 12months was referred to our center because of intractable seizures. The patient was born with birth weight of 3228g after 40weeks of unremarkable gestation. At the age of 2months, she had partial seizures evolving to epileptic spasms. Her electroencephalogram showed hypsarrhythmia. Her seizures were refractory to antiepileptic drugs. At referral to our center at 12months, she had developmental delay (no head control), widely spaced inverted nipples, external strabismus, and bilateral heterochromia of irises. Blood examinations were normal. Brain magnetic resonance imaging findings included cerebral and cerebellar atrophy, thinning of the corpus callosum, and arachnoid pouch. Whole-exome sequencing detected a de novo frameshift mutation c.950delG (p.Gly317Alafs*32) at exon 4 in SLC35A2. Seizures subsided after the second adrenocorticotropic hormones (ACTH) therapy at 18months. At the age of 36months, although she had intellectual disability with no meaningful words, she was seizure-free and was able to sit without support and showed smiling face a lot. CONCLUSION: This report reviewed the clinical features of patients with a SLC35A2 mutation. ACTH therapy may be effective for refractory epilepsy in these patients.