An infant with A20 haploinsufficiency presenting with periodic fever syndrome: A case report.

A20 haploinsufficiency (HA20) is an early-onset autoinflammatory disease caused by loss-of-function variants of the TNFAIP3 gene, which encodes the protein A20. HA20 is typically characterized by Behçet's disease-like clinical symptoms, and patients usually present with a family history. Herein, we report a case of HA20 in a pediatric patient, presenting with periodic fever, abdominal pain, and vomiting, with no family history. This patient also harbored a novel heterozygous frameshift variant c.677del (p.Pro226LeufsTer2) of TNFAIP3. We initiated treatment with an anti-tumor necrosis factor-α agent that did not induce symptom resolution; we thus administered combination therapy, including prednisolone. Remission was then successfully achieved. We suggest that HA20 should be considered when an autoinflammatory disease is suspected and periodic fever syndrome is present, even in the absence of a family history of HA20 or Behçet's disease-like symptoms.

Factors associated with sleep duration among pupils.

BACKGROUND: Sleep shortage has been pervasive among pupils. METHODS: Multiple regression analysis was used to analyze 2,722 questionnaires obtained from grade 5 to 12 pupils, to determine factors associated with sleep duration. RESULTS: Significant regression formulae for sleep duration were obtained for all school types: adjusted R2 / P value were 0.14/<0.001 for elementary school; 0.11/<0.001 for junior high school; 0.06/<0.001 for high school. Longer after-school activities (standardized regression coefficient/ P value were -0.22/<0.001 for elementary school; -0.10/<0.01 for junior high school; -0.18/<0.001 for high school) and more sleepiness (-0.09/<0.001 for elementary school; -0.07/<0.05 for junior high school; -0.07/<0.05 for high school) were significantly associated with reduced sleep duration for all school types. In both elementary and junior high schools, the higher grade (-0.53/<0.001 for elementary school; -0.10/<0.01 for junior high school), and longer weekday screen time (-0.15/<0.001 for elementary school; -0.19/<0.001 for junior high school) were also significantly associated with sleep loss. In elementary school, irregular dinner (-0.07/<0.05), breakfast skipping (-0.11/<0.001), longer weekend screen time (-0.09/<0.05) and better self-reported academic performance (0.07/<0.05) also revealed significant associations with sleep loss. In high school, reduction of sleep duration was also significantly associated with higher standardized body mass index (-0.08/<0.05). CONCLUSIONS: Excessive after-school activity might be considered in association with pupils' sleep reduction.

Insufficient sleep syndrome: An unrecognized but important clinical entity.

BACKGROUND: A sleep clinic for adults and children was established in the Tokyo Bay Urayasu Ichikawa Medical Centre, in August 2012. Given that few sleep clinics are available in Japan specifically for children, this clinic provides the opportunity to provide data on child patients with sleep problems. METHODS: Records of patients who visited the sleep clinic at the Tokyo Bay Urayasu Ichikawa Medical Centre aged ≤20 years at the first visit were retrospectively examined, along with the initial and final diagnoses. RESULTS: Of 2,157 patients who visited the sleep clinic at Tokyo Bay Urayasu Ichikawa Medical Centre between August 2012 and March 2017, 181 were ≤20 years old. In these 181 patients, the most frequent final diagnosis was insufficient sleep syndrome (ISS), n = 56, followed by circadian rhythm sleep-wake disorder, n = 28; insomnia, n = 28; and sleep-related movement disorder, n = 15. CONCLUSIONS: Insufficient sleep produces various brain dysfunctions in both adults and children, and is associated with behavioral, cognitive and physical problems, as well as with atypical early development. Insufficient sleep has also been reported to cause obesity. Insufficient sleep-induced obesity is often associated with the occurrence of metabolic syndrome. More effort is needed to ensure that children are receiving sufficient sleep.

Severe neonatal CMV infection complicated with thrombotic microangiopathy successfully treated with ganciclovir.

We report a neonate of severe cytomegalovirus (CMV) infection who presented vomiting, severe thrombocytopenia and thrombotic microangiopathy (TMA). He showed occasional vomiting at 3 weeks of age and visited us with systemic petechiae at 29 days old. Platelet was markedly decreased to 18,000/µL and fragmented red blood cells were increased in the peripheral blood. Intravenous ganciclovir (GCV) administration was started at 35 days old after detection of CMV in the peripheral blood. His normal values of T-cell receptor excision circles (TREC) and signal joint kappa-deleting recombination excision circles (sjKREC) excluded the possibility of severe immunodeficiency. Congenital CMV infection was denied later, when CMV of the dried blood spot obtained for neonatal mass-screening at 4 days old was proved negative. We provided 6-week treatment with no side effect such as myelosuppression. The left hearing abnormality found at first was improved along with other symptoms. GCV seems to be effective and safe for severe neonatal CMV infection.

Hounsfield unit values of retropharyngeal abscess-like lesions seen in Kawasaki disease.

CONCLUSIONS: Retropharyngeal abscess-like lesions are occasionally seen in computed tomography (CT) imaging of patients with Kawasaki disease (KD) and these patients often undergo unnecessary surgery. We could distinguish the lesions from true abscesses by measuring their Hounsfield unit values (HUs). OBJECTIVE: To distinguish the retropharyngeal abscess-like lesions from true abscesses without any surgical procedure. METHODS: We investigated six cases of KD showing such lesions on CTs, both with and without contrast enhancement (CE). We measured the HUs of those lesions and compared them with those of 10 true abscesses as controls. RESULTS: Abscess-like lesions of KD were well enhanced by CE, whereas abscesses showed virtually no enhancement. The mean HU in the six KD cases was 20.0 ± 4.65 (mean ± SD) on plain CTs and 35.6 ± 4.49 on contrast CTs. In abscesses, it was 30.3 ± 4.42 on plain CTs and 30.3 ± 3.57 on contrast CTs. The difference in HU values [(HU on contrast CT) - (HU on plain CT)] was defined as ΔHU. The mean ΔHU was 15.6 ± 5.36 in the six KD lesions and 0.0 ± 2.93 in abscesses, with statistical significance of p < 0.0001 by Student's t test. Thus, ΔHU value may potentially be a useful parameter for their distinction.

Outcomes of childhood pulmonary arterial hypertension in BMPR2 and ALK1 mutation carriers.

Mutations in the bone morphogenetic protein receptor type 2 (BMPR2) gene and the activin receptor-like kinase 1 (ALK1) gene have been reported in heritable pulmonary arterial hypertension (HPAH) and idiopathic pulmonary arterial hypertension (IPAH). However, the relation between clinical characteristics and each gene mutation in IPAH and HPAH is still unclear, especially in childhood. The aim of this study was to determine, in a retrospective study, the influence and clinical outcomes of gene mutations in childhood IPAH and HPAH. Fifty-four patients with IPAH or HPAH whose onset of disease was at <16 years of age were included. Functional characteristics, hemodynamic parameters, and clinical outcomes were compared in BMPR2 and ALK1 mutation carriers and noncarriers. Overall 5-year survival for all patients was 76%. Eighteen BMPR2 mutation carriers and 7 ALK1 mutation carriers were detected in the 54 patients with childhood IPAH or HPAH. Five-year survival was lower in BMPR2 mutation carriers than mutation noncarriers (55% vs 90%, hazard ratio 12.54, p = 0.0003). ALK1 mutation carriers also had a tendency to have worse outcome than mutation noncarriers (5-year survival rate 64%, hazard ratio 5.14, p = 0.1205). In conclusion, patients with childhood IPAH or HPAH with BMPR2 mutation have the poorest clinical outcomes. ALK1 mutation carriers tended to have worse outcomes than mutation noncarriers. It is important to consider aggressive treatment for BMPR2 or ALK1 mutation carriers.

Liver-specific mitochondrial respiratory chain complex I deficiency in fatal influenza encephalopathy.

We report on a 4-year-old boy who died from influenza encephalopathy. The clinical course and microscopic findings of the autopsied liver were compatible with Reye's syndrome. We examined the mitochondrial respiratory chain function by blue native polyacrylamide gel electrophoresis (BN-PAGE), western blotting, and respiratory chain enzyme activity assays. The activity of liver respiratory chain complex (CO) I was markedly decreased (7.2% of the respective control activity); whereas, the other respiratory chain complex activities were substantially normal (CO II, 57.9%; CO III, 122.3%; CO IV, 161.0%). The activities of CO I-IV in fibroblasts were normal (CO I, 82.0%; CO II, 83.1%; CO III, 72.9%; CO IV, 97.3%). The patient was diagnosed with liver-specific complex I deficiency. This inborn disorder may have contributed to the fatal outcome. We propose that relying only on fibroblast respiratory chain complex activities may lead to the misdiagnosis of liver-specific complex I deficiency.

Ulinastatin, a urinary trypsin inhibitor, for the initial treatment of patients with Kawasaki disease: a retrospective study.

BACKGROUND: Markedly activated neutrophils or higher plasma levels of neutrophil elastase are involved in the poor response to intravenous immunoglobulin (IVIG) and the formation of coronary artery lesions (CAL) in patients with acute Kawasaki disease. We hypothesized that ulinastatin (UTI), by both direct and indirect suppression of neutrophils, would reduce the occurrence of CAL. METHODS AND RESULTS: We retrospectively analyzed the clinical records of patients with Kawasaki disease between 1998 and 2009. Three hundred sixty-nine patients were treated with a combination of UTI, aspirin, and IVIG as an initial treatment (UTI group), and 1178 were treated with a conventional initial treatment, and IVIG with aspirin (control group). The baseline characteristics did not demonstrate notable differences between the two groups. The occurrence of CAL was significantly lower in the UTI group than in the control group (3% versus 7%; crude odds ratio [OR], 0.46; 95% confidence interval [CI], 0.25-0.86; P=0.01). The OR adjusted for sex, Gunma score (the predictive score for IVIG unresponsiveness), and dosage of initial IVIG (1 or 2 g/kg) was 0.32 (95% CI, 0.17-0.60; P<0.001). In addition, most CAL occurred in patients requiring additional rescue treatment and the proportion of those patients was significantly lower in the UTI group than in the control group (13% versus 22%; crude OR, 0.52; 95% CI, 0.38-0.73; P<0.001). The adjusted OR was 0.30 (95% CI, 0.20-0.44; P<0.001). CONCLUSIONS: UTI was associated with fewer patients requiring additional rescue treatment and reduction of CAL in this retrospective study.

Efficacy and safety of carvedilol for heart failure in children and patients with congenital heart disease.

There have been few reports describing the use of carvedilol in children or patients with congenital heart disease. Therefore, its optimal regimen, efficacy, and safety in these patients have not been adequately investigated. Subjects were 27 patients with two functioning ventricles, for whom carvedilol was initiated (from December 2001 to December 2005) to treat heart failure. All patients had failed to respond to conventional cardiac medication. They consisted of 12 males and 15 females, aged 23 days to 47 years (median age: 2 years). Heart failure due to ischemia (myocardial infarction, intraoperative ischemic event) or due to myocardial disease (cardiomyopathy, myocarditis), and heart failure with atrial or ventricular tachyarrhythmia represented 70% of all cases. Carvedilol was initiated at a dose of 0.02-0.05 mg/kg/day, which was increased by 0.05-0.1 mg/kg/day after 2 days, 0.1 mg/kg/day after 5 days, and 0.05-0.1 mg/kg/day every month thereafter with a target dose of 0.8 mg/kg/day. This study retrospectively assessed the efficacy and adverse reactions based on changes of symptoms, cardiothoracic ratio (CTR), left ventricular ejection fraction (LVEF), and human atrial natriuretic peptide (hANP)/b-type natriuretic peptide (BNP) blood levels. The mean follow-up period was 10.2 months (range: 1-46 months). Twenty-six (96.3%) patients showed improvement in symptoms and were discharged from the hospital. However, the remaining one patient failed to respond and died. Significant cardiovascular adverse reaction was seen in none of the patients. The mean CTR decreased from 61.8% +/- 5.3% before treatment to 57.6% +/- 7.4% after treatment (P < 0.05, n = 25), and the mean LVEF improved from 41.4% +/- 23.1% to 61.1% +/- 10.1% (P < 0.05, n = 10), respectively. Mean hANP and BNP levels showed a decrease from 239.1 pg/ml to 118.3 pg/ml and a significant decrease from 437.9 pg/ml to 120.5 pg/ml, respectively (P < 0.05, n = 10). Improvements in these data were also demonstrated when analyzed individually among the pediatric group (aged younger than 18) and the congenital heart disease group. Initiation of carvedilol at a lower dose with more gradual dose escalation, compared with previously reported regimens, might have efficacy with low incidence of adverse effects in pediatric patients and patients with congenital heart disease. Carvedilol may be effective in treating heart failure in children due to ischemia, myocardial disease, and complicated by tachyarrhythmia.