Mutations in Thyroid Hormone Beta Receptor Gene Identified in Children with Clinical Resistance to Thyroid Hormones

Introduction: Patients with resistance to thyroid hormones(RTH) show different clinical features. Several mutations have been identified in them.Objective:To describe patients followed up since 2006 with RTH suspicion evaluated for mutations in thyroid hormone beta receptor(THRß)gene.Methods:Children were followed up in our Endocrinology Department.Patient 1:10-yr-old boy with elevated T3, T4 and free T4, normal TSH in routine thyroid testing requested for overweight. Patient 2:0.7-yr- old boy with Down syndrome and elevated T3, T4 and free T4, normal TSH.Patient 3:Boy with abnormal results on neonatal screening, with elevated T3, T4, free T4 and TSH.Patient 4:4.7?yr-old girl with elevated T3, T4 and free T4, normal TSH in routine thyroid testing requested for low weight.Patient 5: 1-yr- old boy with elevated T3, T4 and free T4, normal TSH in routine thyroid testing requested for low weight.Patient 6:Boy with congenital hypothyroidism diagnosed by screening with elevated T3, T4, free T4 and TSH.Clinical manifestations:Patients 1, 4 and 5 showed palpitations, tachycardia.Familial antecedents: Patient 3 has two brothers with similar RTH profile. Patient 4 had a sister who died at 3 months of age and mother with confirmed RTH. Patient 6 had an aunt with RTH profile.Thyroid ultrasound. All patients had normal gland size except patient 6 who had an hypoplastic gland. Patient 4 showed goiter at follow up.Treatment:Patient 1 received metimazol; patients 1,4 and 5 beta blockers and patient 6 levothyroxine.Molecular biology analysis: genomic DNA was isolated from blood cells and the exons 7-10 of the THRß gene, including the flanking intronic regions were amplified by PCR. DNA sequences from each amplified fragment were performed with the Taq polymerase-based chain terminator method and using the specific forward and reverse THRß primers. Results.Direct sequence analysis revealed a novel missense mutation in exon 10 in patient 3, c.1329G>T transvertion that results in a p.K443N substitution and two known missense mutations: c.1357C>A, p.P453T (Patient 1)in exon 10 and c.949G>A, p.A317T (Patient 4) in exon 9.Conclusion:THRß gene mutations were found in half of the patients with RTH, including a new mutation.Although goiter is a common feature in RTH, only one patient presented it.These findings support the importance of searching THRßgene mutations in suspected individuals to achieve an adequate follow-up and treatment in patients with RHT.Fil: Gonzáles, Viviana. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; ArgentinaFil: Balbi, Viviana A.. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; ArgentinaFil: Morin, Analía. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; ArgentinaFil: Reinoso, Andrea. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; ArgentinaFil: Vitale, Laura. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; ArgentinaFil: Ricci, Jaime. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; ArgentinaFil: Espósito, Mariela. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; ArgentinaFil: Martín, Rodrigo. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; ArgentinaFil: Tournier, Andrea L.. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; ArgentinaFil: Adrover, Ezequiela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; ArgentinaFil: Molina, Maricel Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; ArgentinaFil: Targovnik, Hector Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; ArgentinaFil: Rivolta, Carina Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; ArgentinaXXVIII Congreso Latinoamericano de Endocrinología PediátricaFlorianópolisBrasilSociedad Latinoamericana de Endocrinología Pediátric

COMBIT: protocol of a randomised comparison trial of COMbined modified constraint induced movement therapy and bimanual intensive training with distributed model of standard upper limb rehabilitation in children with congenital hemiplegia

Introduction: Children with congenital hemiplegia often present with limitations in using their impaired upper limb which impacts on independence in activities of daily living, societal participation and quality of life. Traditional therapy has adopted a bimanual training approach (BIM) and more recently, modified constraint induced movement therapy (mCIMT) has emerged as a promising unimanual approach. Evidence of enhanced neuroplasticity following mCIMT suggests that the sequential application of mCIMT followed by bimanual training may optimise outcomes (Hybrid CIMT). It remains unclear whether more intensely delivered group based interventions (hCIMT) are superior to distributed models of individualised therapy. This study aims to determine the optimal density of upper limb training for children with congenital hemiplegia

PET Tracers to Study Clinically Relevant Hepatic Transporters

Peer reviewedPostprin

PREMM: Preterm early massage by the mother: Protocol of a randomised controlled trial of massage therapy in very preterm infants

© 2016 Lai et al.Background: Preterm infants follow an altered neurodevelopmental trajectory compared to their term born peers as a result of the influence of early birth, and the altered environment. Infant massage in the preterm infant has shown positive effects on weight gain and reduced length of hospital stay. There is however, limited current evidence of improved neurodevelopment or improved attachment, maternal mood or anxiety.The aim of this study is to investigate the effects of infant massage performed by the mother in very preterm (VPT) infants.Effects on the infant will be assessed at the electrophysiological, neuroradiological and clinical levels. Effects on maternal mood, anxiety and mother-infant attachment will also be measured. Methods/Design: A randomised controlled trial to investigate the effect of massage therapy in VPT infants. Sixty VPT infants, born at 28 to 32weeks and 6days gestational age, who are stable, off supplemental oxygen therapy and have normal cranial ultrasounds will be recruited and randomised to an intervention (infant massage) group or a control (standard care) group. Ten healthy term born infants will be recruited as a reference comparison group. The intervention group will receive standardised massage therapy administered by the mother from recruitment, until term equivalent age (TEA). The control group will receive care as usual (CAU). Infants and their mothers will be assessed at baseline, TEA, 12months and 24months corrected age (CA), with a battery of clinical, neuroimaging and electrophysiological measures, as well as structured questionnaires, psychoanalytic observations and neurodevelopmental assessments. Discussion: Optimising preterm infant neurodevelopment is a key aim of neonatal research, which could substantially improve long-term outcomes and reduce the socio-economic impact of VPT birth. This study has the potential to give insights into the mother-baby relationship and any positive effects of infant massageon neurodevelopment. An early intervention such as massage that is relatively easy to administer and could alter the trajectory of preterm infant brain development, holds potential to improve neurodevelopmental outcomes in this vulnerable population. Trial registration: Australian New Zealand Clinical Trials Registry: ACTRN12612000335897. Date registered: 22/3/2012

Diffusion MRI of the neonate brain: acquisition, processing and analysis techniques

Diffusion MRI (dMRI) is a popular noninvasive imaging modality for the investigation of the neonate brain. It enables the assessment of white matter integrity, and is particularly suited for studying white matter maturation in the preterm and term neonate brain. Diffusion tractography allows the delineation of white matter pathways and assessment of connectivity in vivo. In this review, we address the challenges of performing and analysing neonate dMRI. Of particular importance in dMRI analysis is adequate data preprocessing to reduce image distortions inherent to the acquisition technique, as well as artefacts caused by head movement. We present a summary of techniques that should be used in the preprocessing of neonate dMRI data, and demonstrate the effect of these important correction steps. Furthermore, we give an overview of available analysis techniques, ranging from voxel-based analysis of anisotropy metrics including tract-based spatial statistics (TBSS) to recently developed methods of statistical analysis addressing issues of resolving complex white matter architecture. We highlight the importance of resolving crossing fibres for tractography and outline several tractography-based techniques, including connectivity-based segmentation, the connectome and tractography mapping. These techniques provide powerful tools for the investigation of brain development and maturation