Yumiko Ninomiya

Genetic Characteristics of Children and Adolescents With Long-QT Syndrome Diagnosed by School-Based Electrocardiographic Screening Programs

Background—A school-based electrocardiographic screening program has been developed in Japan. However, few data are available on the genetic characteristics of pediatric patients with long-QT syndrome who were diagnosed by this program. Methods and Results—A total of 117 unrelated probands aged ⩽18 years were the subjects who were referred to our centers for genetic testing. Of these, 69 subjects diagnosed by the program formed the screened group. A total of 48 subjects were included in the clinical group and were diagnosed with long-QT syndrome–related symptoms, familial study, or by chance. Mutations were classified as radical, of high probability of pathogenicity, or of uncertain significance. Two subjects in the clinical group died. Genotypes were identified in 50 (72%) and 23 (48%) of subjects in the screened and clinical groups, respectively. Of the KCNQ1 or KCNH2 mutations, 31 of 33 (94%) in the screened group and 14 of 15 (93%) in the clinical group were radical and of high probability of pathogenicity. Prevalence of symptoms before (9/69 versus 31/48; P<0.0001) and after (12/69 versus 17/48; P=0.03) diagnosis was significantly lower in the screened group when compared with that in the clinical group although the QTc values, family history of long-QT syndrome, sudden death, and follow-up periods were not different between the groups. Conclusions—These data suggest that the screening program may be effective for early diagnosis of long-QT syndrome that may allow intervention before symptoms. In addition, screened patients should have follow-up equivalent to clinically identified patients.

Current human T‐cell lymphotropic virus type 1 mother‐to‐child transmission prevention status in Kagoshima

The aim of this study was to assess the current human T‐cell lymphotropic virus type 1 (HTLV‐I) mother‐to‐child transmission (MTCT) prevention system in Kagoshima Prefecture. We investigated the rate of carrier pregnant women from obstetrics facilities in Kagoshima by mail in 2012 and compared our results with previous study results. We interviewed carrier pregnant women about their choices for infant nutrition, and we interviewed midwives about the follow‐up system. In 2012, 8719 screening tests were performed, covering 58.1% of all pregnant women in Kagoshima; the rate of carrier pregnant women was 1.3%. Of 59 carriers, 39 chose short‐term breast‐feeding. The HTLV‐I carrier rate among pregnant women in Kagoshima has declined. The current HTLV‐I MTCT prevention system in Kagoshima is effective, but not sufficient. To bring the nutrition methods to completion, various types of support are needed. Further studies will elucidate many unsolved problems concerning MTCT.

A surviving 24-month-old patient with neonatal-onset carnitine palmitoyltransferase II deficiency

The early-onset form of carnitine palmitoyltransferase (CPT) II deficiency has severe outcomes; patients typically die during the newborn period. We report a case of neonatal-onset CPT II deficiency with prolonged survival, exceeding 24 months. The patient was successfully treated by continuous hemodialysis (CHD), which enabled her to overcome repeated crises. We suggest that early intensive treatment, including CHD, is a key for prolonged survival in patients with neonatal-onset CPT II deficiency.

Potential risk factors for dexmedetomidine withdrawal seizures in infants after surgery for congenital heart disease

PURPOSE Few studies are available on withdrawal seizures about dexmedetomidine (DEX). Thus, we retrospectively evaluated the incidence of withdrawal seizures after discontinuation of DEX and examined potential risk factors in infants after cardiovascular surgery. METHODS The medical records of 142 infants who had undergone cardiovascular surgery between April 2010 and November 2013 were examined. Clinical characteristics and usage of DEX were analyzed. DEX withdrawal seizures were evaluated using Withdrawal Assessment Tool - version 1 (WAT-1). All the patients and controls were categorized according to DEX discontinuation strategy, which was either gradual or abrupt. RESULTS Nine patients (6.3%) developed generalized clonic or generalized tonic-clonic seizures accompanied by preceding fever of >38°C approximately four to eight hours following the discontinuation of DEX, and were clinically diagnosed as DEX withdrawal seizures with a median WAT-1 score of 3. Clinical characteristics and operative data were similar, but median cumulative dose and maximum temperature after discontinuation of DEX were significantly higher in infants with withdrawal seizures than in those without (P=0.007 and P<0.001, respectively). Eight of the 9 patients with withdrawal seizures (88.9%) and 20 of the 133 patients (15.0%) with no withdrawal seizures had discontinued DEX abruptly (P<0.001). Cumulative dose and abrupt discontinuation of DEX were significantly associated with DEX withdrawal seizures in infants after cardiovascular surgery (R=0.619, P=0.004). CONCLUSIONS Physicians should be aware that infants who received DEX after cardiovascular surgery had potential to cause withdrawal seizures accompanied by preceding pyrexia after discontinuation of DEX. Higher cumulative dose and abrupt discontinuation of DEX appears to increase the risk for these withdrawal seizures.

Combination of flecainide and propranolol for congenital junctional ectopic tachycardia

Congenital junctional ectopic tachycardia is a rare tachyarrhythmia with high mortality. A pharmacological approach in early infancy is regarded as the first‐line therapeutic option. Pharmacologically, amiodarone alone or in combination with other drugs is the most commonly reported effective agent for congenital junctional ectopic tachycardia, but it has many adverse effects. Here we report the case of a 40‐day‐old infant. The clinical course suggests that combined oral flecainide and propranolol is an effective alternative therapy for early infants. Esophageal lead electrocardiography may give a clear diagnosis of junctional ectopic tachycardia.

Risk factors for symptoms in long QT syndrome patients in a single pediatric center

Long QT syndrome (LQTS) is a leading cause of sudden cardiac death due to arrhythmia in the pediatric population. This study aimed to determine risk factors for the presence of LQTS‐related symptoms in a single pediatric center.

Disruption of Endothelial Cell Homeostasis Plays a Key Role in the Early Pathogenesis of Coronary Artery Abnormalities in Kawasaki Disease

Disruption of endothelial cell homeostasis may be associated with the pathogenesis of coronary artery abnormalities (CAA) in Kawasaki disease (KD). We sought to clarify the poorly understood pathogenic role of endothelial cell survival and death in KD vasculitis. Human umbilical vein endothelial cells (HUVECs) stimulated with sera from KD patients, compared with sera from patients with bacterial infections, exhibited significant increases in cytotoxicity, high mobility group box protein 1 (HMGB-1), and caspase-3/7 and a decrease in phosphorylated Akt/Akt (pAkt/Akt) ratios. HUVECs stimulated with sera from KD patients treated with immunoglobulin (IG) showed significantly decreased cytotoxicity, HMGB-1, and caspase-3/7 levels and increased pAkt/Akt ratios, as compared with results for untreated HUVECs (P < 0.001, P = 0.008, P = 0.040, and P < 0.001, respectively). In HUVECs stimulated with sera from KD patients, the increased cytotoxicity levels and the suppression of increased pAkt/Akt ratios after subsequent IG treatment were closely related to the development of CAA (P = 0.002 and P = 0.035). Our data reveal that shifting the balance toward cell death rather than survival appears to perturb endothelial cell homeostasis and is closely related to the development of CAA. The cytoprotective effects of IG treatment appear to ameliorate endothelial cell homeostasis.