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Background: Telethonin (TCAP) is a Z‐disk protein that maintains cytoskeletal integrity and various signaling pathways in cardiomyocytes. TCAP is shown to modulate α‐subunit of the human cardiac sodium channel (hNav1.5) by direct interactions. Several TCAP variants are found in cardiomyopathies. We sought to investigate whether TCAP variants are associated with arrhythmia syndromes. Methods: Mutational analyses for TCAP were performed in 303 Japanese patients with Brugada syndrome, arrhythmogenic right ventricular cardiomyopathy, and J‐wave pattern ECG. Using patch‐clamp techniques, electrophysiological characteristics of hNav1.5 were studied in HEK‐293 cells stably expressing hNav1.5 and transiently transfected with wild‐type (WT) or variant TCAP. Results: We identified two TCAP variants, c.145G>A:p.E49K and c.458G>A:p.R153H, in four individuals. p.E49K was found in two patients with ARVC or BrS. p.R153H was found in two patients with BrS or J‐wave pattern ECG. No patient had variant hNav1.5. Patch‐clamp experiments demonstrated that peak sodium currents were significantly reduced in cells expressing p.R153H and p.E49K compared with WT‐TCAP (66%, p.R153H; 72%, p.E49K). Voltage dependency of peak IV curve was rightward‐shifted by 5 mV in cells expressing p.E49K compared with WT‐TCAP. Voltage dependency of activation was not leftward‐shifted by p.R153H, while voltage dependency of steady‐state inactivation was leftward‐shifted by p.E49K. Conclusions: We found two TCAP variants in the patients with BrS, J‐wave pattern ECG, and ARVC that can cause loss‐of‐function of the hNav1.5 in heterologous expression systems. Our observation suggests that these variants might impair INa and be associated with the patients' electrophysiological phenotypes. Further studies linking our experimental data to clinical phenotypes are warranted. [ABSTRACT FROM AUTHOR]

Cholestasis in neonates is infrequently associated with Rh isoimmunization, and usually resolves within a month. The suggested pathophysiology is inspissated bile and hepatocellular damage. We report a rare case of refractory cholestasis presenting with cholangiolitis in a newborn with anti-E isoimmunisation. The cholangiolitis was disclosed by immunohistochemical investigation of conjugated hyperbilirubinaemia and by liver biopsy, which showed a number of CD8+ lymphocytes within the portal tract damaging the interlobular bile duct. Bilirubin levels dramatically decreased after 14-day corticosteroid therapy (prednisolone, 2 mg/kg/day) implying that the cause of cholestasis could be immune-mediated cholangiolitis. [ABSTRACT FROM AUTHOR]

Two pregnancies in a woman on oxygen inhalation therapy before pregnancy, due to pulmonary fibrosis and frequent pneumothorax that are secondary to mixed connective tissue disease, were managed safely. As usual for this condition, the patient was rather older and her ordinary daily life was restricted. This is a truly very rare case of a successful pregnancy in these circumstances. In a published work review using key words such as “pregnancy”, “mixed connective tissue disease” and “oxygen inhalation therapy”, no similar case could be found. For the management of such high-risk patients, close cooperation of the obstetrician, clinical immunologist, clinical pneumologist and neonatologist in the same hospital is indispensable. [ABSTRACT FROM AUTHOR]

Aim: Initial presentation with only cervical lymphadenopathy and fever is one of the pitfalls in the diagnosis of Kawasaki disease (KD). As the number of such patients is small, their clinical features have remained uncertain. The purpose of the present study is to characterise the features of such KD patients, especially in comparison with those of patients with common onset. Methods: We conducted a retrospective review of the medical records of 136 consecutive KD patients admitted to Kobe City General Hospital from April of 2000 to March of 2006. Twenty-nine of the 136 patients initially presented with only cervical lymphadenopathy and fever and were classified into the lymphadenopathy-KD (LKD); they were compared with the remaining 107 KD patients with other presentations (other-KD). Results: Age, days of fever to diagnosis, and duration of fever were significantly higher or longer in LKD patients, who also showed higher C-reactive protein levels and neutrophil alkaline phosphatase activity. There were no significant differences between two groups in gender, duration of hospitalization, frequency of high-dose intravenous immunoglobulin (IVIG) administration, coronary artery lesions (CALs), white blood cell or platelet counts, and levels of hemoglobin or albumin on admission. Conclusions: Although a delay in diagnosis and stronger inflammation were found in LKD patients, such differences did not have any significant effect on patients' outcomes as assessed by the frequency of IVIG administration and the presence of CALs. [ABSTRACT FROM AUTHOR]

Carbamoylphosphate synthetase I deficiency (CPS1D) is a urea-cycle disorder characterized by episodes of life-threatening hyperammonemia. Correct diagnosis is crucial for patient management, but is difficult to make from clinical presentation and conventional laboratory tests alone. Enzymatic or genetic diagnoses have also been hampered by difficult access to the appropriate organ and the large size of the gene (38 exons). In this study, in order to address this diagnostic dilemma, we performed the largest mutational and clinical analyses of this disorder to date in Japan. Mutations in CPS1 were identified in 16 of 18 patients with a clinical diagnosis of CPS1D. In total, 25 different mutations were identified, of which 19 were novel. Interestingly, in contrast to previous reports suggesting an extremely diverse mutational spectrum, 31.8% of the mutations identified in Japanese were common to more than one family. We also identified two common polymorphisms that might be useful for simple linkage analysis in prenatal diagnosis. The accumulated clinical data will also help to reveal the clinical presentation of this rare disorder in Japan. [ABSTRACT FROM AUTHOR]

Congenital toxoplasmosis is caused by Toxoplasma gondii. The incidence of death due to congenital toxoplasmosis in Japan from 1974 to 2007 was calculated using the autopsy database of the Japanese Society of Pathology and vital statistics from the Ministry of Health, Labour and Welfare. Two neonatal deaths due to congenital toxoplasmosis were reported during that time. As there were 161 195 neonatal deaths during this period and 32 465 autopsies were performed, the yearly neonatal death from congenital toxoplasmosis was calculated as 2 × 161 195/32 465/34 = 0.29 and the autopsy rate as 32 465/161 195 = 0.2014 (20.14%). The calculated number of annual deaths in infants was 0.82 and in children aged 1-4 years it was 2.09; thus, although few, deaths from congenital toxoplasmosis do still occur in neonates, infants, and young children. Therefore, obstetricians and pediatricians should be aware of the potential for congenital toxoplasmosis, and pregnant women should make every effort to avoid T. gondii infection. [ABSTRACT FROM AUTHOR]