28 research outputs found
Common data elements for clinical research in mitochondrial disease: a National Institute for Neurological Disorders and Stroke project
Objectives The common data elements (CDE) project was
developed by the National Institute of Neurological
Disorders and Stroke (NINDS) to provide clinical researchers
with tools to improve data quality and allow for harmonization
of data collected in different research studies. CDEs have been
created for several neurological diseases; the aim of this project
was to develop CDEs specifically curated for mitochondrial
disease (Mito) to enhance clinical research.
Methods Nine working groups (WGs), composed of international
mitochondrial disease experts, provided recommendations
for Mito clinical research. They initially reviewed
existing NINDS CDEs and instruments, and developed new
data elements or instruments when needed. Recommendations
were organized, internally reviewed by the Mito WGs, and
posted online for external public comment for a period of eight
weeks. The final version was again reviewed by all WGs and
the NINDS CDE team prior to posting for public use
Somatic progenitor cell vulnerability to mitochondrial DNA mutagenesis underlies progeroid phenotypes in Polg mutator mice
Somatic stem cell (SSC) dysfunction is typical for different progeroid phenotypes in mice with genomic DNA repair defects. MtDNA mutagenesis in mice with defective Polg exonuclease activity also leads to progeroid symptoms, by an unknown mechanism. We found that Polg-Mutator mice had neural (NSC) and hematopoietic progenitor (HPC) dysfunction already from embryogenesis. NSC self-renewal was decreased in vitro, and quiescent NSC amounts were reduced in vivo. HPCs showed abnormal lineage differentiation leading to anemia and lymphopenia. N-acetyl-L-cysteine treatment rescued both NSC and HPC abnormalities, suggesting that subtle ROS/redox changes, induced by mtDNA mutagenesis, modulate SSC function. Our results show that mtDNA mutagenesis affected SSC function early but manifested as respiratory chain deficiency in nondividing tissues in old age. Deletor mice, having mtDNA deletions in postmitotic cells and no progeria, had normal SSCs. We propose that SSC compartment is sensitive to mtDNA mutagenesis, and that mitochondrial dysfunction in SSCs can underlie progeroid manifestations
A two-day-old hyperthyroid neonate with thyroid hormone resistance born to a mother with well-controlled Graves’ disease: a case report
<p>Abstract</p> <p>Introduction</p> <p>Resistance to thyroid hormone is a syndrome caused by thyroid hormone receptor β mutations, which are usually inherited in an autosomal-dominant pattern.</p> <p>Case presentation</p> <p>Our patient, a Japanese neonate boy, showed hyperthyroid symptoms at age two days. Although our patient was diagnosed as having resistance to thyroid hormone, his hyperthyroid symptoms continued for two weeks. Therefore, our patient was treated with methimazole and iodine for two weeks from birth, showing no side effects and no symptoms upon treatment. At age 70 days, an R243W mutation in thyroid hormone receptor β was detected in our patient; while absent in his mother, the mutation was present in his father, who never showed any symptoms.</p> <p>Conclusions</p> <p>To the best of our knowledge this is the first case report of a resistance to thyroid hormone in a neonate presenting with hyperthyroid symptoms born to a mother with Graves’ disease and treated with methimazole and iodine. These results suggest that methimazole and iodine may be a good short-term option for treatment.</p