RESUMEN
BACKGROUND: Renal abscess in children is a rare and severe form of infectious kidney disease that is responsible for several serious complications. In this report, we describe a previously healthy 5-year-old girl with a renal abscess caused by extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli (E. coli), which led to bacteremia and renal scarring. CASE PRESENTATION: The patient presented to our department with high fever, headache, vomiting for 2 days and high inflammatory response. We diagnosed her with a urinary tract infection and initiated treatment with ampicillin and cefotaxime. Gram-negative bacilli bacteremia was noted on day 3. On day 4, her fever persisted, and a computed tomography (CT) scan revealed a renal abscess in the left kidney. After identifying the bacteria as ESBL-producing E. coli from the blood culture, we switched to the antibiotic meropenem and continued treatment for 3 weeks. The renal abscess was not drained. Although the renal abscess was successfully treated and it disappeared, a low-density area remained in same lesion on subsequent CT scans and a dimercaptosuccinic acid renal scan performed 4 months after onset revealed renal scarring. CONCLUSION: Given the increasing prevalence of ESBL-producing microorganisms, clinicians should be aware of the possibility of renal abscesses caused by community-acquired ESBL-producing organisms even in previously healthy children. Once a renal abscess is suspected, early diagnosis and management are important for reducing the risk of life-threating complications and renal scarring.
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Bacteriemia , Infecciones por Escherichia coli , Enfermedades Renales , Infecciones Urinarias , Absceso/diagnóstico , Absceso/tratamiento farmacológico , Antibacterianos/uso terapéutico , Bacteriemia/diagnóstico , Bacteriemia/tratamiento farmacológico , Niño , Preescolar , Escherichia coli , Infecciones por Escherichia coli/diagnóstico , Infecciones por Escherichia coli/tratamiento farmacológico , Femenino , Humanos , Factores de Riesgo , Infecciones Urinarias/tratamiento farmacológico , beta-LactamasasRESUMEN
Children with Down syndrome (DS) are at a 20-fold increased risk for acute lymphoblastic leukemia (ALL). Compared to children with ALL and no DS (non-DS-ALL), those with DS and ALL (DS-ALL) harbor uncommon genetic alterations, suggesting DS-ALL could have distinct biological features. Recent studies have implicated several genes on chromosome 21 in DS-ALL, but the precise mechanisms predisposing children with DS to ALL remain unknown. Our integrated genetic/epigenetic analysis revealed that DS-ALL was highly heterogeneous with many subtypes. Although each subtype had genetic/epigenetic profiles similar to those found in non-DS-ALL, the subtype distribution differed significantly between groups. The Philadelphia chromosome-like subtype, a high-risk B-cell lineage variant relatively rare among the entire pediatric ALL population, was the most common form in DS-ALL. Hypermethylation of RUNX1 on chromosome 21 was also found in DS-ALL, but not non-DS-ALL. RUNX1 is essential for differentiation of blood cells, especially B cells; thus, hypermethylation of the RUNX1 promoter in B-cell precursors might be associated with increased incidence of B-cell precursor ALL in DS patients.
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Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Metilación de ADN , Síndrome de Down/complicaciones , Perfilación de la Expresión Génica/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Diferenciación Celular , Niño , Cromosomas Humanos Par 21/genética , Síndrome de Down/genética , Epigénesis Genética , Femenino , Regulación Neoplásica de la Expresión Génica , Predisposición Genética a la Enfermedad , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Cromosoma Filadelfia , Regiones Promotoras Genéticas , Análisis de Secuencia de ADN , Análisis de Secuencia de ARNRESUMEN
Mucopolysaccharidosis type II (MPS II: also called as Hunter syndrome) is an X-linked recessive lysosomal storage disorder characterized by the accumulation of extracellular glycosaminoglycans due to the deficiency of the enzyme iduronate-2-sulfatase (IDS). Previous observations suggested that MPS II can be classified into two distinct disease subtypes: (1) severe type of MPS II involves a decline in the cognitive ability of a patient and (2) attenuated type of MPS II exhibits no such intellectual phenotype. To determine whether such disease subtypes of MPS II could be explained by genetic diagnosis, we analyzed mutations in the IDS gene of 65 patients suffering from MPS II among the Japanese population who were diagnosed with both the accumulation of urinary glycosaminoglycans and a decrease in their IDS enzyme activity between 2004 and 2014. Among the specimens examined, we identified the following mutations: 33 missense, 8 nonsense, 7 frameshift, 4 intronic changes affecting splicing, 8 recombinations involving IDS-IDS2, and 7 other mutations including 4 large deletions. Consistent with the previous data, the results of our study showed that most of the attenuated phenotype was derived from the missense mutations of the IDS gene, whereas mutations associated with a large structural alteration including recombination, splicing, frameshift, and nonsense mutations were linked to the severe phenotype of MPS II. Furthermore, we conducted a homology modeling study of IDS P120R and N534I mutant as representatives of the causative mutation of the severe and attenuated type of MPS II, respectively. We found that the substitution of P120R of the IDS enzyme was predicted to deform the α-helix generated by I119-F123, leading to the major structural alteration of the wild-type IDS enzyme. In sharp contrast, the effect of the structural alteration of N534I was marginal; thus, this mutation was pathogenically predicted to be associated with the attenuated type of MPS II. These results suggest that a combination of the genomic diagnosis of the IDS gene and the structural prediction of the IDS enzyme could enable the prediction of a phenotype more effectively.
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Glicoproteínas/química , Glicoproteínas/genética , Mucopolisacaridosis II/genética , Mucopolisacaridosis II/patología , Mutación , Pueblo Asiatico/genética , Femenino , Predisposición Genética a la Enfermedad , Glicosaminoglicanos/orina , Humanos , Japón , Masculino , Modelos Moleculares , Linaje , Estructura Secundaria de Proteína , Homología Estructural de ProteínaRESUMEN
BACKGROUND: Acute appendicitis is the most common type of acute abdomen that requires surgical intervention in children. According to general pediatric textbooks, the presence of vomiting before abdominal pain is considered a classic patient history item for excluding acute appendicitis. However, its diagnostic performance in the pediatric population has yet to be investigated. METHODS: This was a single-center retrospective observational study involving 134 children who were admitted to the hospital with both abdominal pain and vomiting. The reference standard for appendicitis was defined by computed tomography scanning. The diagnostic performance of "abdominal pain before vomiting" was calculated and compared to those of the Alvarado score and pediatric appendicitis score. RESULTS: The diagnostic performance of "abdominal pain before vomiting" was as follows: sensitivity of 75.3% (95% confidence interval [CI], 64.7-83.6), specificity of 25.0% (95% CI, 15.5-36.7), positive likelihood ratio of 1.00 (95% CI, 0.82-1.22), negative likelihood ratio of 0.99 (95% CI, 0.54-1.79), and diagnostic odds ratio of 1.02 (95% CI, 0.46-2.25). In contrast, the Alvarado score and pediatric appendicitis score (with a threshold of 4 points) demonstrated favorable sensitivity (98.3% [95% CI, 92.4-99.6]), negative predictive value (94.6% [95% CI, 78.4-98.8]), negative likelihood ratio (0.04 [95% CI, 0.01-0.23]), and diagnostic odds ratio (49.9 [95% CI, 6.88-243.2]). CONCLUSION: In this study, "abdominal pain before vomiting" was associated with poor diagnostic performance for ruling out acute pediatric appendicitis. Thus, the diagnosis of acute appendicitis in the pediatric population should be made based on existing validated scoring systems such as the Alvarado score and pediatric appendicitis score.
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Apendicitis , Niño , Humanos , Sensibilidad y Especificidad , Apendicitis/diagnóstico , Apendicitis/diagnóstico por imagen , Valor Predictivo de las Pruebas , Dolor Abdominal/complicaciones , Dolor Abdominal/diagnóstico , Enfermedad Aguda , Vómitos/complicacionesRESUMEN
BACKGROUND: The risk factors for anemia of prematurity (AOP) among late preterm infants are unelucidated. We identified risk factors for declining hemoglobin (Hb) concentration and triggering factors for AOP treatment in infants born at 30-35 gestational weeks. METHODS: From 2012 to 2020, we conducted a single-center retrospective study of infants born at 30-35 weeks of gestation without congenital anomalies or severe hemorrhage. The primary outcome was AOP development, defined by initiation of treatments including red blood cell transfusion, subcutaneous injections of erythropoietin, and iron supplementation. A multivariable logistic regression model was used to investigate potential risk factors for AOP. RESULTS: A total of 358 infants were included. Lower gestational age (odds ratio, 0.19; 95% confidence interval 0.11-0.32), small for gestational age (SGA; 7.17, 2.15-23.9), low maternal Hb level before birth (0.66, 0.49-0.87), low Hb at birth (0.71, 0.57-0.89), and multiple large blood samplings (1.79; 1.40-2.29) showed significantly higher odds for AOP development. CONCLUSIONS: Gestational age, SGA, low maternal Hb before birth, Hb at birth, and high number of large blood samplings were positively associated with AOP development in infants born at 30-35 gestational weeks.
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Anemia Neonatal , Recien Nacido Prematuro , Lactante , Recién Nacido , Humanos , Recién Nacido de Bajo Peso , Estudios Retrospectivos , Factores de RiesgoRESUMEN
A toddler girl presented to our hospital with a fever that lasted for five days. She had no prior history of urinary tract infections or contact with farm animals. Investigations revealed a diagnosis of acute focal bacterial nephritis (AFBN), and we initiated antimicrobial therapy with ampicillin and cefmetazole. On day five, methicillin-resistant coagulase-negative staphylococci were detected in her urine culture, and we changed the antibiotics to vancomycin. Antibiotic therapy was continued for 21 days, with no recurrence of fever. Finally, the bacteria were identified as Staphylococcus (S.) simulans, which is a common farm animal pathogen. Clinicians should be aware of the possibility of AFBN caused by S. simulans, even if the patient has no prior history of close contact with farm animals. If a rare organism is detected in urine culture during AFBN treatment, the patient should be treated with appropriate antibiotics for the pathogen.
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OBJECTIVES: Sepiapterin reductase deficiency (SRD) causes central nervous system symptoms due to dopamine and serotonin depletion because sepiapterin reductase plays an important role in tetrahydrobiopterin biosynthesis. SRD cannot be detected by newborn screening because of the absent hyperphenylalaninemia. To diagnose SRD biochemically, confirmation of reduced monoamine metabolites and elevated sepiapterin in the cerebrospinal fluid (CSF) has been considered necessary, because a past study showed no elevation of urine sepiapterin. Recently, however, the elevation of urine sepiapterin in SRD was reported. METHODS: We developed a fast method to measure sepiapterin and creatinine simultaneously using high-performance liquid chromatography with fluorescence and ultraviolet detection. Urine sepiapterin and creatinine were measured in three SRD patients, two SRD carriers, four SRD siblings, and 103 non-SRD patients. RESULTS: In the three SRD cases, concentrations of urine sepiapterin were 1086, 914, and 575 µmol/mol creatinine (upper limit: 101.7 µmol/mol creatinine), and were markedly higher than those in other groups. CSF sepiapterin concentration was also measured in one SRD case and it was 4.1 nmol/L (upper limit: 0.5 nmol/L). CONCLUSIONS: The simultaneous determination of urine sepiapterin and creatinine appears helpful for the diagnosis of SRD. This assay system can also be used to measure sepiapterin in the CSF.
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Distonía , Pterinas , Creatinina , Distonía/diagnóstico , Humanos , Recién Nacido , Errores Innatos del Metabolismo , Trastornos Psicomotores , Pterinas/metabolismoRESUMEN
BACKGROUND: Niemann-Pick type C (NPC) is a lysosomal lipid storage disease with mutation of NPC1/NPC2 genes, which transport lipids in the endosome and lysosome, and various neurological symptoms. NPC patients also develop hepatosplenomegaly or liver disorder in the neonatal period, and 10% suffer severe liver failure. Neonatal hemochromatosis (NH) is a liver disorder characterized by hepatic and extrahepatic siderosis. Although the etiology of NH is unclear, recent reports suggest that the gestational alloimmune mechanism is the cause of NH. Herein, we report a Japanese NPC patient initially diagnosed as NH. CASE REPORT: A 5-day-old boy was transferred to our hospital with severe cholestatic liver failure. Congenital infections and metabolic screening were negative, and NH was suspected. However intra and extrahepatic siderosis were not found. As his liver deteriorated rapidly, liver transplantation was performed at 19â¯days old. The explanted liver showed cirrhosis, and strong C5b-9 complex staining of hepatocytes, so NH was diagnosed. From the age of one and a half years, he developed regression, vertical supranuclear gaze palsy and cataplexy. Fibroblast filipin staining was strong, blood oxysterol was high, and there were compound heterozygous mutations in NPC1,p.[(F288L)];[(K1206N)]. The patient was then diagnosed as NPC and started on miglustat. CONCLUSION: Neonatal liver failure was initially diagnosed as NH. Later, the patient developed various neurological symptoms characteristic of NPC. Neurological follow-up of children who develop NH is required.
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Hemocromatosis/diagnóstico , Enfermedades del Recién Nacido/diagnóstico , Fallo Hepático/diagnóstico , Enfermedad de Niemann-Pick Tipo C/diagnóstico , Humanos , Recién Nacido , MasculinoRESUMEN
Hunter syndrome is a lysosomal disease characterized by deficiency of the lysosomal enzyme iduronate-2-sulfatase (I2S). It has an estimated incidence of approximately 1 in 1,62,000 live male births. We report a case of Hunter syndrome diagnosed by an otorhinolaryngologist. To our knowledge, this is the first study diagnosed by an otorhinolaryngologist despite the fact that otorhinolaryngological symptoms manifest at a young age in this disease. The patient was a 4-year-old boy. He underwent adenotonsillectomy. Intubation was difficult, and he had some symptoms which are reasonable as a mucopolysaccharidosis. The otorhinolaryngologist should play an integral role in the multidisciplinary approach to the diagnosis and management of many children with MPS (mucopolysaccharidoses) disorders.
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Infantile Refsum disease (IRD) is a rare autosomal recessive disorder of peroxisome biogenesis characterized by generalized peroxisomal metabolic dysfunction, including accumulation of very long-chain fatty acids (VLCFAs) and phytanic acid (PA), as well as decreased plasmalogen contents (PL). An effective therapy for this intractable disease has not been established, and only supportive management with docosahexaenoic acid supplementation and low PA diet has been reported so far. A boy of 3 years and 8 months presented with facial dysmorphism, transaminitis, and psychomotor retardation. Biochemical analysis showed elevated PA and VLCFAs, with reduced PL in the serum. Immunofluorescence study of fibroblasts from the patient indicated a mosaic pattern of catalase-positive and -negative particles, and molecular analysis revealed compound heterozygous mutations of PEX6 The failure of medical management to prevent the progression of clinical symptoms and abnormal biochemistry prompted us to consider liver transplantation (LT). With the chances of receiving a deceased donor liver being poor, we performed a living-donor LT from the patient's heterozygous mother. At 6-month follow-up, the patient's serum PA levels had normalized. VLCFAs and PL levels had declined and increased, respectively. To the best of our knowledge, this is the second reported case in which IRD was treated by living-donor LT by using a heterozygous donor. Only long-term follow-up will reveal if there is any clinical improvement in the present case. With the liver being a major site for peroxisomal pathways, its replacement by LT may work as a form of partial enzyme therapy for patients with IRD.
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Trasplante de Hígado , Donadores Vivos , Enfermedad de Refsum Infantil/cirugía , ATPasas Asociadas con Actividades Celulares Diversas , Adenosina Trifosfatasas/genética , Preescolar , Ácidos Grasos/sangre , Femenino , Heterocigoto , Humanos , Imagen por Resonancia Magnética , Masculino , Mutación , Ácido Fitánico/sangre , Enfermedad de Refsum Infantil/genética , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patologíaRESUMEN
X-linked adrenoleukodystrophy (X-ALD) is a rare inherited metabolic disorder characterized by an impaired beta-oxidation of very long chain fatty acids in the peroxisomes. Recent studies have suggested that 1-hexacosanoyl-2-hydroxy-sn-glycero-3-phosphocholine (Lyso-PC 26:0) can be a sensitive biomarker for X-ALD. Although approximately 10-fold increase in the concentration of Lyso-PC 26:0 in DBSs from X-ALD-affected individuals were reported, whether the carriers might be distinguished from the healthy controls remained unclear. To address this question, we have validated previously developed LC-MS/MS-based analytical procedures using QC DBS. We found that the recovery of Lyso-PC 26:0 from the QC DBSs was 73.6 ± 0.3% when 2 µM of Lyso-PC 26:0 was spiked into the blood. Based on this result, the amounts of Lyso-PC 26:0 in the controls and ALD-affected individuals were 0.090 ± 0.004 (n = 11) and 1.078 ± 0.217 (n = 4) pmol/DBS, respectively. Interestingly, the concentration of Lyso-PC 26:0 in the carriers were 0.548 ± 0.095 pmol/DBS (n = 3), indicating that the carriers and the healthy controls can be distinguished. These results suggest that LC-MS/MS-based technique can be used for the detection of asymptomatic carriers and X-ALD-affected subjects in the newborn screening.