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Context Thyroglobulin (Tg), encoded by TG , is essential for thyroid hormone synthesis. TG defects result in congenital hypothyroidism (CH). Most reported patients were born before the introduction of newborn screening (NBS). Objective We aimed to clarify the phenotypic features of patients with TG defects diagnosed and treated since the neonatal period. Methods We screened 1061 patients with CH for 13 CH-related genes and identified 30 patients with TG defects. One patient was diagnosed due to hypothyroidism-related symptoms and the rest were diagnosed via NBS. Patients were divided into 2 groups according to their genotypes, and clinical characteristics were compared. We evaluated the functionality of the 7 missense variants using HEK293 cells. Results Twenty-seven rare TG variants were detected, including 15 nonsense, 3 frameshift, 2 splice-site, and 7 missense variants. Patients were divided into 2 groups: 13 patients with biallelic truncating variants and 17 patients with monoallelic/biallelic missense variants. Patients with missense variants were more likely to develop thyroid enlargement with thyrotropin stimulation than patients with biallelic truncating variants. Patients with biallelic truncating variants invariably required full hormone replacement, whereas patients with missense variants required variable doses of levothyroxine. Loss of function of the 7 missense variants was confirmed in vitro. Conclusion To our knowledge, this is the largest investigation on the clinical presentation of TG defects diagnosed in the neonatal period. Patients with missense variants showed relatively mild hypothyroidism with compensative goiter. Patients with only truncating variants showed minimal or no compensative goiter and required full hormone replacement. [ABSTRACT FROM AUTHOR]

Objective Serum amino-terminal propeptide of C-type natriuretic peptide ( NT-pro CNP) levels have been proposed as a biomarker of linear growth in healthy children. The usefulness of NT-pro CNP in patients with achondroplasia ( ACH)/hypochondroplasia ( HCH) remains to be elucidated. The objective was to study whether serum NT-pro CNP level is a good biomarker for growth in ACH/ HCH and other patients of short stature. Design This was a longitudinal cohort study. Patients Sixteen children with ACH (aged 0·4-4·3 years), six children with HCH (2·7-6·3 years), 23 children with idiopathic short stature ( ISS) (2·2-9·0 years), eight short children with GH deficiency ( GHD) (2·9-6·8 years) and five short children born small for gestational age ( SGA) (2·0-6·6 years). Patients with ACH/ HCH received GH treatment for 1 year. Measurements Serum NT-pro CNP levels and height were measured. Results NT-pro CNP levels positively correlated with height velocity in these short children ( P < 0·05, r = 0·27). NT-pro CNP levels inversely correlated with age in children with ISS alone ( P < 0·01, r = −0·55). Serum NT-pro CNP levels in patients with ACH/ HCH were increased 3 months following the initiation of GH treatment ( P < 0·05). Height SDS gain during GH treatment for 1 year was positively correlated with the changes in NT-pro CNP levels after the initiation of GH ( P < 0·01, r = 0·72). Conclusion Serum NT-pro CNP levels may be a good biomarker to indicate the effect of GH treatment on growth in patients with ACH/ HCH at least in the first year and height velocity in short stature patients. [ABSTRACT FROM AUTHOR]

Pharmacokinetics, clinical efficacy and safety of teicoplanin (TEIC) were evaluated in pediatric and neonate patients with MRSA sepsis in the dosages approved in overseas. The administrated dose for pediatrics patients was 10 mg/kg once at hour 0, 12 and 24, followed by every 24 hours intervals. In neonates patients, first dose was 16 mg/kg, then 8 mg/kg every 24 hours intervals. 1. Pharmacokinetic results. All 17 patients (9 neonates and 8 pediatrics) who received TEIC were evaluated for pharmacokinetics. Trough concentrations were analyzed in 16 patients (9 neonates and 7 pediatrics) excluding one patient for lack of measurement of drug concentration at day 7. No patient with a concentration exceeding 60 micrograms/mL in peak or trough concentrations were reported. Mean concentrations in trough at day 3, 4 and 7 in neonates were 15.2, 14.7 and 17.8 micrograms/mL, and in pediatrics were 12.5, 12.2 and 13.1 micrograms/mL, respectively. These results were similar to those reported in foreign pediatrics and neonates patients. 2. Efficacy and safety results. Since no patient was excluded, all patients were evaluated for efficacy and safety. Microbiological efficacy as well as clinical cure were secondarily evaluated in 2 patients for whom MRSA was isolated from blood. Clinical efficacy rate was 76.5% (13/17) and number of cases in judgments of excellent, good, fairly improved and no change were 12, 1, 3 and 1 cases respectively. The patients for whom MRSA was isolated from blood were judged as MRSA eradicated case and cured without any additional anti-MRSA drugs. Adverse events were reported in 2 neonates and 3 pediatric patients. Possibly related adverse events to study drug (adverse drug reactions) were: 1 case of respiratory disorder, thrombocythemia, gamma-GTP increased, GOT increased and GPT increased in 3 pediatrics. These results suggest that an application of overseas dose regimen of TEIC for neonate and pediatrics is appropriate in Japan.