[Show abstract][Hide abstract] ABSTRACT: It has been established that enhanced computed tomography (CT) and 99mTc-dimercaptosuccinic acid renal scintigraphy (99mTc-DMSA scintigraphy) used in conjunction with single-photon emission CT is a useful tool for the diagnosis of acute pyelonephritis (APN). The utility of non-enhanced magnetic resonance imaging (MRI), however, has not been investigated extensively for the diagnosis of APN or renal abscess in children. We describe the case of a 23-month-old boy with suspected APN who received non-enhanced MRI. Whole body diffusion-weighted imaging (DWI) was used, and a background body-signal suppression sequence was applied. High-intensity focal lesions were identified on DWI and low-intensity lesions on the apparent diffusion coefficient map in the acute phase. This case suggested that non-enhanced MRI could be a useful tool for the diagnosis of APN in children, because it can avoid the risks of not only radiation exposure but also nephrogenic systemic fibrosis associated with gadolinium-based contrast agents, especially in infants.
Pediatrics International 06/2014; 56(3). · 0.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Various humoral factors have been proposed as causal agents of idiopathic steroid-sensitive nephrotic syndrome (ISSNS), resulting in varying data. We used mass spectrometry (MS) to analyze serum proteins in a search for proteins that might be involved in ISSNS pathophysiology.
Serial serum samples were obtained from 33 children with ISSNS. Samples were collected during Phase A1 [the acute phase prior to steroid treatment (STx)], Phase A2 (remission with STx), and Phase A3 (remission without any medication). We also included age- and sex-matched two control groups comprising children with normal urinalysis (Group B) and children with a nephrotic syndrome other than ISSNS (Group C). The urinary protein/urinary creatinine (UP/UCr) ratios were not statistically different between Phase A1 and Group C. Samples were analyzed using surface-enhanced laser desorption/ionization time of flight MS.
A total of 207 peptide ion peaks were detected in the range of m/z 2000-10000. Four peptide ions (m/z 6444, 6626, 8695, and 8915) were detected at significant elevation during Phase A1 compared with Phase A2, Phase A3, and Group C. The intensities of m/z 6444 and 8695 were higher in Phase A3 than in Group B. There were significant correlations between the intensities of m/z 6626, 8695, and 8915 and UP/UCr levels. The m/z 8695 was identified as apolipoprotein AII.
Apolipoprotein AII was detected as a protein associated with the UP/UCr levels in pediatric ISSNS. Our findings present an interesting starting point for further investigation into the pathophysiology of ISSNS.
Clinical and Experimental Nephrology 03/2014; · 1.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We report the case of a 5-year-old Japanese girl who initially had acute disseminated encephalomyelitis (ADEM) and was positive for the myelin oligodendrocyte glycoprotein (MOG) antibodies and developed unilateral optic neuritis (ON) 71 days after ADEM onset. The patient's serum was positive for the anti-MOG antibodies from the onset of ADEM to the development of ON. This phenotype has been reported in only two previous articles, and the specific mechanism of action of the anti-MOG antibodies is not yet understood. Our case suggests that the anti-MOG antibody can be associated with the pathogenesis of ADEM followed by ON. Thus, patients with ADEM who test positive for the anti-MOG antibody may be at risk of developing subsequent ON.
[Show abstract][Hide abstract] ABSTRACT: Interstitial deletion of 12q21 has been reported in four cases, which share several common clinical features, including intellectual disability (ID), low-set ears, and minor cardiac abnormalities. Comparative genomic hybridization (CGH) analysis using the Agilent Human Genome CGH 180K array was performed with the genomic DNA from a two-year-old Japanese boy with these symptoms, as well as hypoplasia of the corpus callosum. Consequently, a 14 Mb deletion at 12q21.2-q21.33 (nt. 77 203 574-91 264 613 bp), which includes 72 genes, was detected. Of these, we focused on LIN7A, which encodes a scaffold protein that is important for synaptic function, as a possible responsible gene for ID, and we analyzed its role in cerebral cortex development. Western blotting analyses revealed that Lin-7A is expressed on embryonic day (E) 13.5, and gradually increases in the mouse brain during the embryonic stage. Biochemical fractionation resulted in the enrichment of Lin-7A in the presynaptic fraction. Suppression of Lin-7A expression by RNAi, using in utero electroporation on E14.5, delayed neuronal migration on postnatal day (P) 2, and Lin-7A-deficient neurons remained in the lower zone of the cortical plate and the intermediate zone. In addition, when Lin-7A was silenced in cortical neurons in one hemisphere, axonal growth in the contralateral hemisphere was delayed; development of these neurons was disrupted such that one half did not extend into the contralateral hemisphere after leaving the corpus callosum. Taken together, LIN7A is a candidate gene responsible for 12q21-deletion syndrome, and abnormal neuronal migration and interhemispheric axon development may contribute to ID and corpus callosum hypoplasia, respectively.
PLoS ONE 01/2014; 9(3):e92695. · 3.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: An objective biomarker is a compelling need for the early diagnosis of attention deficit hyperactivity disorder (ADHD), as well as for the monitoring of pharmacological treatment effectiveness. The advent of fNIRS, which is relatively robust to the body movements of ADHD children, raised the possibility of introducing functional neuroimaging diagnosis in younger ADHD children. Using fNIRS, we monitored the oxy-hemoglobin signal changes of 16 ADHD children (6 to 13 years old) performing a go/no-go task before and 1.5 h after MPH or placebo administration, in a randomized, double-blind, placebo-controlled, crossover design. 16 age-and gender-matched normal controls without MPH administration were also monitored. Relative to control sub-jects, unmedicated ADHD children exhibited reduced activation in the right inferior frontal gyrus (IFG) and middle frontal gyrus (MFG) during go/no-go tasks. The reduced right IFG/MFG activation was acutely nor-malized after MPH administration, but not after placebo administration. The MPH-induced right IFG/MFG activation was significantly larger than the placebo-induced activation. Post-scan exclusion rate was 0% among 16 right-handed ADHD children with IQ > 70. We revealed that the right IFG/MFG activation could serve as a neuro-functional biomarker for monitoring the acute effects of methylphenidate in ADHD children. fNIRS-based examinations were applicable to ADHD children as young as 6 years old, and thus would con-tribute to early clinical diagnosis and treatment of ADHD children.
[Show abstract][Hide abstract] ABSTRACT: The ribosomal protein S6 kinase, 90 kb, polypeptide 3 gene (RPS6KA3) is responsible for Coffin-Lowry syndrome (CLS), which is characterized by intellectual disability (ID) and facial and bony abnormalities. This gene also affects nonsyndromic X-linked ID and nonsyndromic X-linked ID without bony abnormalities. Two families have been previously reported to have genetic microduplication including RPS6KA3. In the present study, we used array-comparative genomic hybridization (CGH) analysis with Agilent Human genome CGH 180K and detected a 584-kb microduplication spanning 19.92-20.50 Mb of Xp22.12 (including RPS6KA3) in the members of one family, including three brothers, two sisters, and their mother. The 15-year-old male proband and one of his brothers had mild ID and localization-related epilepsy, whereas his other brother presented borderline intelligence quotient (IQ) and attention-deficit-hyperactivity disorder (ADHD). One sister presented pervasive development disorder (PDD). Analysis of this family suggests that RPS6KA3 duplication is responsible for mild ID, ADHD, and localization-related epilepsy, and possibly for PDD.Journal of Human Genetics advance online publication, 29 August 2013; doi:10.1038/jhg.2013.88.
Journal of Human Genetics 08/2013; · 2.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Williams-Beuren syndrome (WBS) is a multisystemic genetic disorder caused by a contiguous gene deletion at 7q11.23. We report a severely affected WBS patient with cerebral and cerebellar dysplasia as well as hypertrophic cardiomyopathy. Microarray comparative genomic hybridization (aCGH) detected a deletion on 7q11.23 expanding from RP11-614D7 to RP11-137E8, which is a typical deletion in WBS. To the best of our knowledge, this is the first case report of a WBS patient with severe congenital central nervous system anomaly and progressive hypertrophic cardiomyopathy. The relationship between the genes deleted in WBS and a CNS anomaly plus hypertrophic cardiomyopathy requires further analysis.
[Show abstract][Hide abstract] ABSTRACT: A patient with acute lymphoblastic leukemia who was hypersensitive to native Escherichia coli L-asparaginase (L-asp) underwent readministration of the L-asp without serious adverse effects for 11 doses using a desensitization protocol every time. Monitoring of anti-L-asp antibody and L-asp activity levels revealed that the serum L-asp activity was below the effective levels during the administration of first 6 to 7 doses because of extremely high levels of anti-L-asp IgG. Sustained L-asp activity was attained since the eighth dose was administered, when the antibody levels were <5 U/mL. L-asp activity levels in patients with L-asp hypersensitivity should be monitored during the desensitization courses to ensure a sufficient L-asp activity.
Journal of Pediatric Hematology/Oncology 05/2013; · 0.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Deletion of the monoamine oxidase (MAO)-A and MAO-B was detected in two male siblings and in their mother. The approximately 800-kb deletion, extending from about 43.0MB to 43.8MB, was detected by array comparative genomic hybridization analysis. The MAOA and MAOB genes were included in the deletion, but the adjacent Norrie disease gene, NDP, was not deleted. The boys had short stature, hypotonia, severe developmental delays, episodes of sudden loss of muscle tone, exiting behavior, lip-smacking and autistic features. The serotonin levels in their cerebrospinal fluid were extremely elevated. Another set of siblings with this deletion was reported previously. We propose recognition of MAOA/B deletion syndrome as a distinct disorder.
[Show abstract][Hide abstract] ABSTRACT: Contiguous ABCD1 DXS1357E deletion syndrome (CADDS) is a contiguous deletion syndrome involving the ABCD1 and DXS1357E/BAP31 genes on Xq28. Although ABCD1 is responsible for X-linked adrenoleukodystrophy (X-ALD), its phenotype differs from that of CADDS, which manifests with many features of Zellweger syndrome (ZS), including severe growth and developmental retardation, liver dysfunction, cholestasis and early infantile death. We report here the fourth case of CADDS, in which a boy had dysmorphic features, including a flat orbital edge, hypoplastic nose, micrognathia, inguinal hernia, micropenis, cryptorchidism and club feet, all of which are shared by ZS. The patient achieved no developmental milestones and died of pneumonia at 8 months. Biochemical studies demonstrated abnormal metabolism of very long chain fatty acids, which was higher than that seen in X-ALD. Immunocytochemistry and Western blot showed the absence of ALD protein (ALDP) despite the presence of other peroxisomal proteins. Pathological studies disclosed a small brain with hypomyelination and secondary hypoxic-ischemic changes. Neuronal heterotopia in the white matter and leptomeningeal glioneuronal heterotopia indicated a neuronal migration disorder. The liver showed fibrosis and cholestasis. The thymus and adrenal glands were hypoplastic. Array comparative genomic hybridization (CGH) analysis suggested that the deletion was a genomic rearrangement in the 90-kb span starting in DXS1357E/BACP31 exon 4 and included ABCD1, PLXNB3, SRPK3, IDH3G and SSR4, ending in PDZD4 exon 8. Thus, the absence of ALDP, when combined with defects in the B-cell antigen receptor associated protein 31 (BAP31) and other factors, severely affects VLCFA metabolism on peroxisomal functions and produces ZS-like pathology.
[Show abstract][Hide abstract] ABSTRACT: Mutations in the synaptic adhesion protein CADM1 (RA175/SynCAM1) are associated with autism spectrum disorder (ASD), a neurodevelopmental disorder of uncertain molecular origin. Cadm1-knock out (KO) mice exhibit smaller cerebella with decreased number of synapse of Purkinje cells and some ASD-like symptoms, including impaired ultrasonic vocalization. In this study, we examined the alteration of the Cadm1 synaptic complex in the mouse cerebellum at post-natal stages. The C-terminal peptide of Cadm1 associated with Mupp1 at PSD-95/Dlg/ZO-1 (PDZ)(1-5), a scaffold protein containing 13 PDZ domains, which interacted with gamma-aminobutyric acid type B receptor (GABBR)2 at PDZ13, but not with PSD-95. The GABBR2 was detected in a set of proteins interacting with Cadm1 C-terminal. Cadm1 colocalized with Mupp1 and GABBR2 on the dendrites of Purkinje cells in the molecular layers of the developing cerebellum and on the dendrites of hippocampal neurons cultured in vitro. These observations suggest that the Cadm1 synaptic receptor complex, including Mupp1-GABBR2, is located on the dendrites of Purkinje cells. The amount of GABBR2 protein, but not mRNA, was increased in the cerebella of Cadm1 KO mice, suggesting that lack of Cadm1 does not affect transcription of GABBR2, but may stabilize the Mupp1-GABBR2 complex; the Mupp1-GABBR2 interaction may be stabilized by conformational change in Mupp1 or association with other adhesion molecules and by anchorage to the post-synaptic membrane. Up-regulation of GABBR2 in the cerebellum in the absence of CADM1 may be associated with ASD pathogenesis.
Journal of Neurochemistry 09/2012; · 3.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We report the case of a boy with myoclonic epilepsy with ragged-red fibers (MERRF) who had astatic seizures since 2years of age and later developed ataxia, absence seizures, and myoclonus. Almost homoplasmic A8344G mutation of mitochondrial DNA (m.8344A>G mutation) was detected in lymphocytes. He developed late-onset Leigh syndrome (LS) when he contracted pneumonia at 6years. He developed bulbar palsy and deep coma. MRI demonstrated lesions in the brainstem, basal ganglia, and cerebral cortex. Three similar cases have been reported; two carried the almost-homoplasmic m.8344A>G mutation in muscle tissue. These suggested that almost homoplastic m.8344A>G mutation developed clinical phenotype of MERRF in the early stage and late-onset Leigh syndrome in the late course of the disease.
[Show abstract][Hide abstract] ABSTRACT: Subtelomeric deletions of 1q44 cause mental retardation, developmental delay and brain anomalies, including abnormalities of the corpus callosum (ACC) and microcephaly in most patients. We report the cases of six patients with 1q44 deletions; two patients with interstitial deletions of 1q44; and four patients with terminal deletions of 1q. One of the patients showed an unbalanced translocation between chromosome 5. All the deletion regions overlapped with previously reported critical regions for ACC, microcephaly and seizures, indicating the recurrent nature of the core phenotypic features of 1q44 deletions. The four patients with terminal deletions of 1q exhibited severe volume loss in the brain as compared with patients who harbored interstitial deletions of 1q44. This indicated that telomeric regions have a role in severe volume loss of the brain. In addition, two patients with terminal deletions of 1q43, beyond the critical region for 1q44 deletion syndrome exhibited delayed myelination. As the deletion regions identified in these patients extended toward centromere, we conclude that the genes responsible for delayed myelination may be located in the neighboring region of 1q43.
Journal of Human Genetics 06/2012; 57(9):593-600. · 2.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Various agents have been suggested as causal or associated factors in the pathogenesis of Kawasaki disease (KD); however, the underlying factors of KD remain unknown. Plasma exchange is one of the most effective treatments for the acute phase of KD. This indicates that plasma may contain factors associated with the pathogenesis of KD. To search for proteins that may be involved in KD pathogenesis, we analyzed serum proteins with surface-enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF MS). Serum samples were obtained from 17 KD patients. Serum from six of the patients was collected during acute phase before acetylsalicylic acid (ASA) and intravenous immunoglobulin administration (phase A1), during remission with ASA (phase A2), and during remission without any medication (phase A3). Serum from the remaining 11 patients was collected for phases A1 and A2 only. There were two age- and sex-matched control groups comprising 8 afebrile healthy children (group B) and 8 febrile children with several infectious diseases (group C). There were no statistical differences in laboratory examination between phase A1 and group C except for albumin level, alanine aminotransferase, or sodium level. Serum samples were analyzed by SELDI-TOF MS after purification. We detected five peaks, i.e., those were specifically increased or decreased during phase A1, and identified 1 of these as α1-antitrypsin (α1-AT). α1-AT can inhibit neutrophil elastase activity. This elastase is thought to play a role in coronary artery damage. Our findings present an interesting starting point for further investigations into the pathophysiology of KD.
[Show abstract][Hide abstract] ABSTRACT: Patients with hemophilia and high titers of inhibitors are hard to treat during bleeding events and consequently are more likely to incur high treatment costs and to experience deterioration in quality of life. We report here the case of a boy with hemophilia A and high titers of inhibitors who responded well to prophylactic activated prothrombin complex concentrate (APCC) treatment. Previously, he had to be hospitalized frequently because of painful bleeding of target joints of the knee and ankle. At the age of 4 years and 3 months, APCC prophylaxis at a dose of 60 U/kg, three times a week, was initiated together with on-demand therapy with recombinant factor VIIa. This reduced the frequency and severity of bleeding and ended the need for hospitalization. This, together with a decreased requirement for bypass agents, APCC treatment significantly reduced the cost of treatment for this patient.
Blood coagulation & fibrinolysis: an international journal in haemostasis and thrombosis 02/2012; 23(3):235-7. · 1.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A 10-year-old Japanese boy developed acute hepatitis with high levels of serum Torque teno virus DNA and marked lymphocytopenia, especially CD4 T-lymphocytopenia. Although the total lymphocyte counts rose as the patient recovered from hepatitis, this was largely because of a marked rise in CD8 cells. In contrast, CD4 cells recovered poorly, resulting in a further striking fall in the CD4/8 ratio. Two months later, the patient developed hepatitis-associated aplastic anemia. He was successfully treated with immunosuppressive therapy, which normalized the lymphocyte subset proportions. T-cell subsets analysis at the onset of hepatitis might be useful for predicting development of hepatitis-associated aplastic anemia.
Journal of Pediatric Hematology/Oncology 01/2012; 34(5):375-7. · 0.97 Impact Factor