A Case of Ulcerative Colitis Induced by Paraneoplastic Syndrome?

Background: Paraneoplastic syndromes often cause endocrine, neurological, cutaneous, and hematologic pathologies, and cases with digestive symptoms as prominent cases are rare. Case Description: A 1-year-old child admitted to the emergency department with severe abdominal distension was later diagnosed with sacrococcygeal yolk cystoma with ulcerative colitis. After symptomatic management, surgical removal of the tumor, and JEB chemotherapy, the symptoms of ulcerative colitis disappeared completely. After 7 years of follow-up, the child grew and developed well, and there was no recurrence of tumor and ulcerative colitis. Conclusion: Yolk sac tumor with ulcerative colitis is a rare paraneoplastic syndrome with complex clinical manifestations.

MOGS-CDG: Quantitative analysis of the diagnostic Glc3 Man tetrasaccharide and clinical spectrum of six new cases.

Congenital disorders of glycosylation (CDG) are a clinically and biochemically heterogeneous subgroup of inherited metabolic disorders. Most CDG with abnormal N-glycosylation can be detected by transferrin screening, however, MOGS-CDG escapes this routine screening. Combined with the clinical heterogeneity of reported cases, diagnosing MOGS-CDG can be challenging. Here, we clinically characterize ten MOGS-CDG cases including six previously unreported individuals, showing a phenotype characterized by dysmorphic features, global developmental delay, muscular hypotonia, and seizures in all patients and in a minority vision problems and hypogammaglobulinemia. Glycomics confirmed accumulation of a Glc3 Man7 GlcNAc2 glycan in plasma. For quantification of the diagnostic Glcα1-3Glcα1-3Glcα1-2Man tetrasaccharide in urine, we developed and validated a liquid chromatography-mass spectrometry method of 2-aminobenzoic acid (2AA) labeled urinary glycans. As an internal standard, isotopically labeled 13 C6 -2AA Glc3 Man was used, while labeling efficiency was controlled by use of 12 C6 -2AA and 13 C6 -2AA labeled laminaritetraose. Recovery, linearity, intra- and interassay coefficients of variability of these labeled compounds were determined. Furthermore, Glc3 Man was specifically identified by retention time matching against authentic MOGS-CDG urine and compared with Pompe urine. Glc3 Man was increased in all six analyzed cases, ranging from 34.1 to 618.0 µmol/mmol creatinine (reference <5 µmol). In short, MOGS-CDG has a broad manifestation of symptoms but can be diagnosed with the use of a quantitative method for analysis of urinary Glc3 Man excretion.

[Analysis of child with pyruvate carboxylase deficiency type A due to compound heterozygous variants of the PC gene].

OBJECTIVE: To analyze the clinical features and genetic basis for a child with pyruvate carboxylase deficiency type A (PCD-A). METHODS: Clinical data of the child was retrospectively analyzed. The child and his parents were subjected to trio-whole exome sequencing, and candidate variants were verified by bioinformatics analysis. RESULTS: The child was admitted due to fever with vomiting and disturbance of consciousness. His clinical manifestations included severe decompensated acidosis, hypotension and intractable shock. Cranial MRI showed abnormal signal in the brain, and chest X-ray revealed acute pulmonary edema. DNA sequencing revealed that he has harbored compound heterozygous variants of the PC gene, namely c.182T>C (p.I61T) and c.2581G>A (p.V861M), which were respectively inherited from his father and mother. Neither variant was retrievable in the ClinVar and HGMD databases. Through prediction of protein structure, both variants may affect the functional stability of the protein product. CONCLUSION: The compound heterozygous variants of the PC gene probably underlay the PCD-A in this child. Combined with the clinical features, the child was ultimately diagnosed as PCD-A. Above finding has enriched the spectrum of PC gene variation underlying PCD-A.

Ascorbic acid and hydrocortisone synergistically inhibit septic organ injury via improving oxidative stress and inhibiting inflammation.

BACKGROUND: The current study aimed to investigate the effect of the combination of ascorbic acid (AscA) and hydrocortisone (Hyd) on septic organ injury and its potential mechanism. METHOD: Sepsis was induced in mice by a single intraperitoneal injection of lipopolysaccharides. RESULTS: AscA and Hyd combined showed more effective protection of the injured liver and kidney in septic mice by decreasing alanine aminotransferase, aspartate aminotransferase, serum urea nitrogen, and serum creatinine and ameliorating pathological manifestations than Hyd or AscA alone. AscA showed a mild inhibitory effect on the secretion of proinflammatory cytokines (tumor necrosis factor-alpha (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6)). However, Hyd showed a weak regulatory effect on septic oxidative stress markers (malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px)). However, the combination of AscA and Hyd showed a more powerful inhibitory effect on the septic inflammatory response and oxidative stress than Hyd or AscA alone by decreasing TNF-α, IL-1ß, and IL-6 and regulating MDA, SOD, and GSH. In an in vitro study, cotreatment of RAW 264.7 macrophages with Hyd and AscA sharply reduced reactive oxygen species (ROS) generation and synergistically inhibited TNF-α, IL-1ß, and IL-6 secretion, which could be abolished by additional stimulation with the ROS donor 3-nitropropionic acid (3-NP). As expected, cotreatment of macrophages with Hyd and AscA synergistically inhibited the activation of p38 MAPK and p-p65, and the effect could be reversed by additional stimulation with 3-NP. CONCLUSIONS: AscA and Hyd synergistically protect the kidney and liver from injury by inhibiting the inflammatory response and oxidative stress. The powerful inhibitory effects of AscA on oxidative stress contribute to the synergistic anti-inflammatory action.

Epidemiology of Cardiopulmonary Arrest and Outcome of Resuscitation in PICU Across China: A Prospective Multicenter Cohort Study.

Objective: To investigate the epidemiology and the effectiveness of resuscitation from cardiopulmonary arrest (CPA) among critically ill children and adolescents during pediatric intensive care unit (PICU) stay across China. Methods: A prospective multicenter study was conducted in 11 PICUs in tertiary hospitals. Consecutively hospitalized critically ill children, from 29-day old to 18-year old, who had suffered from CPA and required cardiopulmonary resuscitation (CPR) in the PICU were enrolled (December 2017-October 2018). Data were collected and analyzed using the "in-hospital Utstein style." Neurological outcome was assessed with the Pediatric Cerebral Performance Category (PCPC) scale among children who had survived. Factors associated with the return of spontaneous circulation (ROSC) and survival at discharge were evaluated using multivariate logistic regression. Results: Among 11,599 admissions to PICU, 372 children (3.2%) had CPA during their stay; 281 (75.5%) received CPR, and 91 (24.5%) did not (due to an order of "Do Not Resuscitate" requested by their guardians). Cardiopulmonary disease was the most common reason for CPA (28.1% respiratory and 19.6% circulatory). The most frequent initial dysrhythmia was bradycardia (79%). In total, 170 (60.3%) of the total children had an ROSC, 91 had (37.4%) survived till hospital discharge, 28 (11.5%) had survived 6 months, and 19 (7.8%) had survived for 1 year after discharge. Among the 91 children who were viable at discharge, 47.2% (43/91) received a good PCPC score (1-3). The regression analysis results revealed that the duration of CPR and the dose of epinephrine were significantly associated with ROSC, while the duration of CPR, number of CPR attempts, ventricular tachycardia/ventricular fibrillation (VT/VF), and the dose of epinephrine were significantly associated with survival at discharge. Conclusion: The prevalence of CPA in critically ill children and adolescents is relatively high in China. The duration of CPR and the dose of epinephrine are associated with ROSC. The long-term prognosis of children who had survived after CPR needs further improvement.

Assessment of continuous neutrophil CD64 index measurement for diagnosing sepsis and predicting outcome in a Chinese pediatric intensive care unit: a prospective study.

BACKGROUND: The high affinity immunoglobulin-Fc fragment receptor I CD64 on neutrophils is widely assumed to be a useful biomarker in the early identification of sepsis, and it improves outcomes. We aimed to determine its ability to diagnose sepsis and predict its prognosis with continuous measurements. METHODS: A total of 335 patients admitted to a Chinese PICU were prospectively stratified into two groups according to the presence of sepsis (defined by clinical criteria for sepsis) between 2018 and 2019. Serum concentrations of the nCD64 index, C-reactive protein (CRP), and procalcitonin (PCT) were measured. Sensitivity, specificity and receiver operating characteristic (ROC) curves were calculated to evaluate the diagnostic value for sepsis. A multiple logistic regression model was used to estimate the prognostic value of continuous nCD64 index measurement for in-hospital death. RESULTS: The baseline nCD64 index and levels of PCT and CRP were significantly higher in septic children than in nonseptic children (P<0.05). The nCD64 index presented a higher sensitivity (0.90), specificity (0.78) and area under the ROC curve [0.91 (0.90, 0.93)] than CRP and PCT in discriminating septic children with an optimal cutoff value of 5.78. The nCD64 index decreased with the progression of sepsis, and the baseline nCD64 index was strongly associated with in-hospital death (OR: 2.18, 95% CI: 1.02-4.74). Moreover, the more rapidly the nCD64 index declined, the lower the in-hospital death rate was (OR: 0.89, 95% CI: 0.63-1.35) after adjusting for the baseline nCD64 index and other confounders. CONCLUSIONS: The nCD64 index was not only effective for the early diagnosis of childhood sepsis but also positively associated with the prognosis of sepsis. Moreover, the nCD64 decline was inversely associated with the in-hospital death rate.

A rare case of Pseudomonas aeruginosa bacteremia in a newborn with 58 perforations in the small intestine.

BACKGROUND: Community-acquired infections of Pseudomonas aeruginosa (P. aeruginosa) occur very rarely. CASE PRESENTATION: P. aeruginos was detected in cultures of venous blood and peritoneal exudate of a newborn with 58 perforations in the small intestine. Intravenous administration of imipenem cilastratin sodium and emergency abdominal surgery were performed. The patient fully recovered and was discharged 17 days after the operation. CONCLUSIONS: Mild symptoms of systemic infections in newborns may delay the diagnosis. Early detection and timely treatment are the key to improved prognosis.

Fatal congenital tuberculosis owing to late diagnosis of maternal tuberculosis: case report and review of congenital tuberculosis in China.

Congenital tuberculosis (TB) is rare and the prognosis is poor if not detected early. The diagnosis is often delayed owing to non-specific clinical presentation, misdiagnosis and undiagnosed maternal TB during pregnancy. A 12-day-old girl presented with a 5-day history of fever, cough, poor feeding and respiratory distress. Her mother had a cough and fever at 30 weeks gestation which was managed empirically as community-acquired pneumonia without a TB workup. Immediately postpartum, her mother developed a high fever and shortness of breath and required admission to the intensive care unit. The infant was separated from her mother after delivery. The infant's chest radiograph showed bilateral miliary nodules. Thoracic and abdominal computed tomography (CT) showed multiple enlarged lymph nodes and congenital TB was suspected. Early morning gastric aspirate and sputum (obtained through a suction tube) were positive for acid-fast bacilli on smear microscopy and subsequently Mycobacterium tuberculosis was cultured from both specimens. Lumbar puncture was performed and cerebrospinal fluid (CSF) was compatible with TB meningitis. TB-polymerase chain reaction (TB-PCR) was positive. Her mother was diagnosed with miliary TB on postpartum day 17. Both were given anti-TB chemotherapy. Unfortunately, despite the treatment, the infant died from multiple organ dysfunction syndrome (MODS) caused by congenital TB at the age of 14 days. This case highlights the importance of screening pregnant women for TB in regions where it is highly prevalent. A high index of suspicion of maternal and congenital TB is critical to early diagnosis, especially in such regions.

IDDCA syndrome in a Chinese infant due to GNB5 biallelic mutations.

Herein, we present a Chinese infant with an early-onset intellectual developmental disorder with cardiac arrhythmia syndrome. A 6-month-old boy visited our hospital because of convulsions and paroxysmal cyanosis for 1 day. Mental development analysis showed that the patient had a neurodevelopmental delay. Frequent seizures occurred, and ECG monitoring demonstrated severe cardiac arrhythmia. Whole-exome sequencing showed that the infant had two compound heterozygous variants, NM_016194:c.458G>A/p.Cys153Tyr and NM_016194:c.1032C>A/p.Tyr344*, in GNB5. The first variant was inherited from his mother, while the other one was a de novo variant. Haplotype analysis indicated that the de novo variant was located in the paternal chromosome. Structural modeling indicated that both mutations could influence the interaction of GNB5 with its binding protein. Our study expanded the known genetic and phenotypic spectrum of GNB5-associated diseases, by presenting a Chinese male infant with IDDCA.

[Risk factors and prognosis of acute kidney injury in children with sepsis in pediatric intensive care unit].

OBJECTIVE: To investigate the risk factors and prognosis of acute kidney injury (AKI) in children with sepsis in pediatric intensive care unit (PICU). METHODS: A retrospective analysis of clinical data of PICU sepsis children in Anhui Children's Hospital from May 2015 to May 2018 was performed. The children were divided into AKI group and non-AKI group according to whether AKI occurred within 48 hours of PICU [referring to the diagnostic criteria for Kidney Disease: Improving Global Outcomes (KDIGO)]. The general data, physiological data and clinical outcomes of the two groups were compared; Logistic regression analysis was used to analyze the risk factors of AKI in children with sepsis and the prognostic factors. RESULTS: AKI occurred in 55 of 127 children with sepsis, the incidence of AKI was 43.3%, and the overall mortality was 28.3% (36/127), with 41.8% (23/55) in AKI group and 18.1% (13/72) in non-AKI group. (1) Compared with non-AKI group, oxygenation index, albumin, the pediatric critical illness case score (PCIS) and urine volume in AKI group were significantly decreased, while cystatin C, procalcitonin (PCT), prothrombin time (PT), activated partial thromboplastin time (APTT), pediatric multiple organ dysfunction score (P-MODS), the proportions of mechanical ventilation, vasoactive drug use, shock, septic shock and mortality were significantly increased, while there was no difference in age, gender, mean arterial pressure (MAP), white blood cell count (WBC) and C-reactive protein (CRP) between the two groups. Multivariate Logistic regression analysis showed that low serum albumin [odds ratio (OR) = 0.627, 95% confidence interval (95%CI) = 0.495-0.794, P = 0.000] and homocystatin C (OR = 2.641, 95%CI = 1.157-6.032, P = 0.021) were risk factors for AKI in children with sepsis. (2) Compared with the survival group of children with sepsis AKI, the proportion of mechanical ventilation, septic shock, vasoactive drug use, positive balance ratio of liquid for 72 hours, 6-hour lactate clearance rate < 10%, and AKI 3-stage patients in the death group of children with sepsis AKI were significantly increased. Multivariate Logistic regression analysis showed that 72-hour positive liquid balance (OR = 8.542, 95%CI = 1.956-37.307, P = 0.004) and 6-hour lactate clearance rate < 10% (OR = 5.980, 95%CI = 1.393-25.676, P = 0.016) were risk factors for the death of children with sepsis AKI. CONCLUSIONS: Serum albumin and cystatin C should be closely monitored in children with sepsis. Early detection and intervention of positive fluid balance and low lactate clearance rate can reduce the mortality of AKI in children with sepsis.

Compound heterozygous variants in MOGS inducing congenital disorders of glycosylation (CDG) IIb.

This study is to present two Chinese siblings who were diagnosed with congenital disorders of glycosylation (CDG) IIb because of mannosyl-oligosaccharide glucosidase (MOGS) deficiency. The siblings visited our hospital due to "pulmonary infection". Facial dysmorphism including long eyelashes, blepharophimosis, depressed nasal bridge, and high palate was noted. Head MRI of the elder sister showed increased signals on T1W1, bilateral frontal gyrus stenosis, and thin corpus callosum. Both cases presented progressive hepatomegaly and elevated hepatic enzymes. Low immunoglobulin was discovered in the siblings. Compound heterozygous variants of NM_006302:c.1239_1267dup,p.Asp414Leufs*17, c.544 G > A,p.Gly182Arg, and c.1698C > A,p.Asp566Glu in MOGS were identified. Structural modeling demonstrated that the mutations were pathogenic to MOGS. Our study enriched the genetic and phenotypic spectrum of MOGS-CDG, and for children with facial dysmorphism, postnatal dyspnea, seizures, motor developmental delay, hypotonia, and immunological or gastrointestinal dysfunction, this disease should be highly suspected.

[Etiology and prognosis of thrombocytopenia in children: a case analysis in 683 children within 10 years of pediatric intensive care unit].

OBJECTIVE: To analyze the etiology and prognosis of children with thrombocytopenia (TP) in pediatric intensive care unit (PICU). METHODS: The data of children with TP (exclusion of congenital and unknown TP) admitted to PICU of Anhui Provincial Children's Hospital from January 2008 to December 2017 was analyzed retrospectively. According to the age of onset, the children were divided into infantile group (29 days to less than 1 year), early childhood group (1 to less than 3 years), preschool group (3 to less than 6 years), school age group (6 to less than 10 years) and puberty group (more than 10 years). Moreover, according to the lowest platelet count (PLT), the children were divided into PLT ≤ 20×109/L group, PLT (21-50)×109/L group and PLT > (50-100) ×109/L group. The distribution and mortality of TP were analyzed, and the relationship between age, PLT decrease and prognosis were analyzed by Pearson method. RESULTS: Among 6 725 children admitted to PICU in our hospital from January 2008 to December 2017, there were 683 children with TP, with the incidence of 10.2%. Among 683 children with TP, there were 387 males and 296 females, with the median age of 2.72 (0.61, 3.08) years, and 92 children died, with a total mortality of 13.5%. Analysis of primary disease showed that TP caused by non-hematological malignant tumor disease accounted for 73.9%, with the mortality of 11.1% (56/505). TP induced by hematological malignant tumor disease accounted for 21.4%, with the mortality of 24.7% (36/146). Pseudothrombocytopenia accounted for 0.6%, with the mortality of 0% (0/4). Other children who gave up treatment accounted for 4.1%. It was shown by further analysis that multiple organ dysfunction syndrome (MODS) caused by TP associated with non-hematological malignant tumor disease accounted for 26.9%, with the mortality of 15.4% (21/136). Sepsis, severe trauma, pneumonia, central nervous system infection and disseminated intravascular coagulation (DIC) accounted for 17.4%, 16.6%, 12.7%, 11.7% and 11.5%; with the mortality of 8.0% (7/88), 2.4% (2/84), 0% (0/64), 20.3% (12/59) and 24.1% (14/58), respectively. The main causes of TP associated with hematological malignant tumor disease were hemophagocytic syndrome [accounting for 27.4%, with the mortality of 32.5% (13/40)] and bone marrow inhibition [accounting for 21.2%, with the mortality of 25.8% (8/31)]. The younger were the children with TP, the higher would be the mortality. The mortality of infantile group was significantly higher than that of early childhood group, preschool group, school age group and puberty group [18.8% (53/282) vs. 14.0% (28/200), 6.7% (7/104), 4.3% (4/92), 0% (0/5), all P < 0.01]. The lower was the PLT, the higher would be the mortality. The mortality of PLT ≤ 20×109/L group was significantly higher than that of PLT (21-50)×109/L group and PLT > (50-100)×109/L group [18.1% (39/215) vs. 13.0% (32/247), 9.5% (21/221), both P < 0.05]. It was shown by correlation analysis that there was no association between age and 28-day death time in children with TP (r = -0.037, P = 0.727), but PLT was positively correlated with 28-day death time in children with TP (r = 0.844, P = 0.010). CONCLUSIONS: MODS, infection, sepsis, severe trauma and DIC are the common causes of TP in PICU. The younger are the children with TP, the lower is the PLT, and the worse would be the prognosis.

Whole-exome Sequencing Helps the Diagnosis and Treatment in Children with Neurodevelopmental Delay Accompanied Unexplained Dyspnea.

Neurodevelopmental delay accompanied unexplained dyspnea is a highly lethal disease in clinic. This study is to investigate the performance characteristics of trio whole exome sequencing (Trio-WES) in a pediatric setting by presenting our patient cohort and displaying the diagnostic yield. A total of 31 pediatric patients showing neurodevelopmental delay accompanied unexplained dyspnea were admitted to our hospital and referred for molecular genetic testing using Trio-WES. Eight genes namely MMACHC, G6PC, G6PT, ETFDH, OTC, NDUFAF5, SLC22A5, and MAGEL2 were suspected to be responsible for the onset of the clinical symptoms and 6 variants were novel. Standard interpretation according to ACMG guideline showed that the variants were pathogenic. Finally, diagnosis of methylmalonic aciduria and homocystinuria, glycogen storage disease, ornithine transcarbamylase deficiency, glutaric acidemia II, mitochondrial complex 1 deficiency, carnitine deficiency, and Schaaf-Yang syndrome was made in 12 out of the 31 patients. Trio-WES is an effective means for molecular diagnosis of infantile neurodevelopmental delay accompanied unexplained dyspnea. As for molecular etiology identification, when routine potential monogenetic inheritance patterns including de novo, autosomal recessive, autosomal dominant, and X-linked recessive inheritance analysis is negative, physicians should take into account imprinted genes.

[Effects of different sedation regimens on sedation and inflammatory response in critically ill children with multiple trauma].

OBJECTIVE: To compare the sedation and anti-inflammatory effects of dexmedetomidine and midazolam on critical ill children with multiple trauma. METHODS: A prospective randomized controlled trial was conducted. Sixty-five critical ill children with multiple trauma admitted to pediatric intensive care unit (PICU) of Anhui Province Children's Hospital from January 2014 to September 2016 were enrolled, who were randomly divided into dexmedetomidine group (33 cases) and midazolam group (32 cases). Children of both groups received sufentanil for analgesia. Children in dexmedetomidine group firstly received 1.0 µg/kg intravenous bolus of dexmedetomidine for 10 minutes, then continuous infusion of 0.2-0.7 µg×kg-1×h-1, while in midazolam group children received 1-5 µg×kg-1×min-1 of midazolam in continuous infusion. The goal of sedation was to maintain a Richmond agitation-sedation scale (RASS) score of -1 to 0. The level of serum interleukin (IL-6, IL-8, IL-10, IL-1ß), tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) were detected by enzyme linked immunosorbent assay (ELISA) at 24, 48, 72 hours after treatment, and the duration of mechanical ventilation, ratio of continuous renal replacement therapy (CRRT), length of stay in the PICU, ratio of sepsis and multiple organ failure (MOF) and mortality were also recorded. RESULTS: Compared with midazolam, dexmedetomidine decreased the level of pro-inflammatory cytokines and increased the level of anti-inflammatory cytokines. At 24 hours after treatment, the levels of serum IL-1ß, TNF-α significantly decreased and IL-10 significantly increased [IL-1ß (ng/L): 6.48±2.89 vs. 8.07±3.14, TNF-α (µg/L): 11.25±5.21 vs. 15.44±5.97, IL-10 (ng/L): 12.10±5.35 vs. 9.58±4.71, all P < 0.05]. At 48 hours after treatment, the levels of serum IL-6, IL-8, IL-1ß, TNF-α and CRP significantly decreased and IL-10 significantly increased [IL-6 (ng/L): 209.67±80.49 vs. 336.31±123.94, IL-8 (ng/L): 229.09±80.81 vs. 298.28±90.25, IL-1ß (ng/L): 7.31±3.02 vs. 8.74±3.17, TNF-α (µg/L): 12.52±4.79 vs. 16.58±5.98, CRP (g/L): 47.82±24.92 vs. 72.35±31.71, IL-10 (ng/L): 12.90±5.42 vs. 10.01±4.79, all P < 0.05]. At 72 hours after treatment, the levels of serum IL-8 and CRP significantly decreased [IL-8 (ng/L): 234.64±96.24 vs. 290.28±103.97, CRP (g/L): 53.24±29.12 vs. 86.58±38.30, both P < 0.05]. Compared with midazolam, dexmedetomidine could significantly reduce the duration of mechanical ventilation (days: 4.7±1.3 vs. 6.6±2.1), length of PICU stay (days: 9.5±2.7 vs. 12.3±3.9, both P < 0.05), and the ratio of sepsis (33.3% vs. 53.1%, P < 0.05). But there were no significant differences in ratio of CRRT (18.2% vs. 18.8%), MOF (9.1% vs. 18.8%) and mortality (6.1% vs. 12.5%) between two groups (all P > 0.05). CONCLUSIONS: Compared with midazolam, dexmedetomidine had better efficacy in the treatment of severe multiple trauma in children and reduce the level of inflammation.

Novel NFU1 Variants Induced MMDS Behaved as Special Leukodystrophy in Chinese Sufferers.

Multiple mitochondrial dysfunctions syndrome (MMDS) is an autosomal recessive disorder of systemic energy metabolism. This study is to present the diagnosis of two MMDS Chinese sufferers. Physical and auxiliary examination was performed. Next generation sequencing (NGS) was conducted to identify candidate causal genes and Sanger sequencing was adopted to validate the variants detected. Fluorescence quantitative polymerase chain reaction (FQ-PCR) amplification was carried out to testify allelic loss existence. Structural investigation was performed to study the possibility of the candidate variants for disease onset. Physical examination showed that the children were with neurological impairment. Auxiliary examination demonstrated energy metabolism disturbance and abnormal brain signals. NGS found that the probands had homozygous mutation of c.545 + 5G > A and compound heterozygous variants of exon 4 deletion and c.721G > T in NFU1, respectively. NFU1 was considered as candidate molecular etiology and indicating that the kids were with MMDS. Sanger sequencing confirmed the variants. FQ-PCR amplification characterized that patient 1 had a de novo allele mutation while patient 2 inherited from his parents. Structural investigation demonstrated that the variants were possible for MMDS occurrence. This is the first report of patients diagnosed as MMDS with novel mutation types from the Asia-Pacific region.

[Report of a case with late-onset ornithine transcarbamylase deficiency with gas chromatography-mass spectrometry and DNA sequencing confirmation and literatures review].

OBJECTIVE: To discuss the clinical characteristics, diagnosis and treatment management of ornithine transcarbamylase deficiency (OTCD). METHOD: Data of the clinical diagnosis and treatment of a case with OTCD were analyzed, and the domestic and international literature was reviewed. RESULT: (1) The case was a boy, 8 years old; and the initial symptoms were vomiting and reduced consciousness for a day after eating a lot of eggs as previous similar history. The level of blood ammonia was 2 500 µmol/L. The patient was treated with fasting, high-calorie fluid intravenous infusion, reducing blood ammonia. However, the disease further aggravated and the patient died due to brain hernia and central cardiovascular failure. Finally, he was confirmed as OTCD through urine testing by gas chromatography-mass spectrometry, plasma amino acid examination (plasma arginine and citrullineurine reduced, orotic acid raised) and genetic testing (OTC c.386G>A p. (Arg129His)). (2) Data of 55 case reports about diagnosis and treatment outcome including 65 OTCD cases' clinical data in domestic and abroad reports in nearly 5 years. Their ages ranged from 3 days to 49 years; the common symptoms were vomiting and encephalopathy; both urine tests were positive in 52 cases; pathogenic genes had less repeated loci and located at Xp21.1 in 42 cases detected by OTC gene test; all of which had gene mutation. CONCLUSION: The acute onset OTCD begins with the symptoms of vomiting and unconsciousness, with rapid rise of blood ammonia level. OTCD may cause high mortality.

[Analysis of serious respiratory complications in PICU in children with measles].

OBJECTIVE: To evaluate the characteristics of the serious complications of 17 cases with measles in ICU. METHOD: Seventeen cases with measles with serious complications in ICU in Anhui Provincial Children's Hospital were recruited from May 2012 to May 2013. Clinical characteristics, image finding, and prognosis were analyzed retrospectively. IgM antibody was positive in all the 17 cases, which included 9 male cases, 8 female cases, and their age was from 2 months to 10 years. RESULT: All the 17 patients received mechanical ventilation because of severe respiratory distress within 1 week of onset, of which 14 cases were complicated with acute respiratory distress syndrome (acute ARDS), 6 cases of tension pneumothorax, 3 cases were complicated with bronchitis, laryngeal obstruction III degrees, and totally 7 cases died. The survived 10 patients were followed up for 1 year, 1 patient with localized pneumothorax, bronchopleural fistula, 1 case of mild pulmonary fibrosis, 1 case of acute laryngitis with persistent hoarseness, and mild inspiratory dyspnea were found. The remaining 7 cases fully recovered. Fourteen cases failed to inoculate measles vaccine. CONCLUSION: A higher risk of death and poor prognosis were found in children with measles who needed to be treated in PICU, especially for ARDS with pneumothorax. Laryngitis needed long time to cure and had weaning difficulties, and the case associated with pleural effusion or bronchopleural fistula must be treated with surgery, and the patients easily develop secondary bacterial infection.

Clinical characteristics and genetic analysis of two cases with Leigh syndrome with acute pulmonary hemorrhage as predominant manifestation / 中华儿科杂志

<p><b>OBJECTIVE</b>To analyze clinical and imaging features and genetic characteristics of Leigh syndrome with emergent pulmonary edema.</p><p><b>METHOD</b>The clinical features and imaging data of 2 cases (1 male, 1 female) seen in Anhui Provincial Children's Hospital from 2012 to 2014 were analyzed and summarized. Venous blood samples were sent to Guangzhou Jinyu Medical Examination Center for genetic analysis. Peripheral blood DNA was extracted and amplified, then sent to a sequencing facility for presence of genetic mutation by comparing with the reference sequence (NC_012920.1).</p><p><b>RESULT</b>(1) The first patient was a 7 months old boy. The second patient was a 7 months and 21 days old girl. They were presented with abnormal respiration and pulmonary hemorrhage required mechanical ventilation. The first patient had a similar attack after 4 months of his birth, whose psychomotor development was normal, and no abnormal neurological findings. The value of blood lactate was 1.58 mmol/L. The value of pyruvic acid was 0.25 mmol/L. The value of cerebrospinal fluid lactate was 6. 4 mmol/L, which was an abnormal increase. The second patient had abnormal nervous system development, which included motor development retardation and hypotonia. The value of blood lactate was 6. 8 mmol/L, pyruvic acid was 0.31 mmol/L. Cerebrospinal fluid lactate was 8.2 mmol/L. (2) Imaging data: chest X-ray revealed double lung effusion. Bilateral caudate nucleus and lentiform nucleus had high signal, and bilateral internal capsule forelimbs were affected in DWI sequence of head MRI. Hemispheres, basal ganglia, cerebral peduncle, cerebellum, pons, and splenium of corpus callosum had multiple abnormal signals in head MRI of the second patient. NAA peak showed significantly reduced lesion area in magnetic resonance blood-flow scanning, and Cho peak increased significantly, which were double lactate-peak. (3) Genetic testing: ATPase6 m.9185 t > C mutation was found in case 1 that was consistent with Leigh syndrome pathogenesis. Hybrid mutations (m. 10191 t > C) in mitochondrial DNA was found in case 2. Two cases with the diagnosis of Leigh syndrome was clear. They were given combined therapy, such as mechanical ventilation, limited fluid to alleviate lung exudation, coenzyme Q10, and L-carnitine. The illness of case 1 relapsed after discharge. But in case 2, there was no improvement. They both died after treatment was given up.</p><p><b>CONCLUSION</b>Neurological symptoms were common in Leigh syndrome, in which acute lung hemorrhage was rarely reported. Timely ventilator support can temporarily save lives, but fatality rate is high and prognosis is poor.</p>

[Negative pressure pulmonary edema with upper airway obstruction: analysis of 3 patients].

OBJECTIVE: To investigate the clinical characteristics and treatment of negative pressure pulmonary edema (NPPE) with upper airway obstruction (UAO) in children. METHOD: Data of 3 cases with NPPE and UAO in pediatric intensive care unit (PICU) from Mar, 2007 to May, 2013 were analyzed. RESULT: (1) Two cases were male and 1 was female with age respectively 6, 16 and 30 months.One had airway foreign body , 1 laryngitis , and 1 retropharyngeal abscess. The onset of NPPE varied from 5 to 40 minutes following relief of obstruction. (2) NPPE presented with acute respiratory distress with signs of tachypnea, tachycardia, 2 of the 3 with pink frothy pulmonary secretions, progressively decreased oxygen saturation, rales on chest auscultation and wheezing. (3) NPPE chest radiograph showed diffuse interstitial and alveolar infiltrates, images confirmed pulmonary edema. (4) All these patients received these therapeutic measures including mechanical ventilation, retaining high PEEP, diuretics, limiting the fluid input volume to 80-90 ml/ (kg×d) on the basis of circulation stability. The rales on chest auscultation disappeared after 10, 6, 12 hours. The ventilators of 2 patients were removed within 24 hours, in another case it was removed 50 hours later because of secondary infection. All patients were cured and discharged without complication. CONCLUSION: NPPE progresses very fast, characterized by rapid onset of symptoms of respiratory distress after UAO, with pulmonary edema on chest radiograph. The symptoms resolve rapidly if early support of breath and diuretics are applied properly.