Resistance to Thyroid Hormone Alpha in an 18-Month-Old Girl: Clinical, Therapeutic, and Molecular Characteristics

Thyroid : Official Journal of the American Thyroid Association
Anja van GuchtA S Paul van Trotsenburg

Abstract

Recently, the first patients with resistance to thyroid hormone alpha (RTHα) due to inactivating mutations in the thyroid hormone receptor alpha (TRα) were identified. These patients are characterized by growth retardation, variable motor and cognitive defects, macrocephaly, and abnormal thyroid function tests. The objective was to characterize a young girl (18 months old) with a mutation in both TRα1 and TRα2, and to study the effects of early levothyroxine (LT4) treatment. The patient was assessed clinically and biochemically before and during 12 months of LT4 treatment. In addition, the consequences of the mutation for TRα1/2 receptor function were studied in vitro. At 18 months of age, the patient presented with axial hypotonia, delayed motor development, severe growth retardation, and abnormally elevated triiodothyronine (T3)/thyroxine (T4) ratios. RTHα was suspected, and concomitantly a c.632A>G/p.D211G missense mutation was identified, affecting both the TRα1 and TRα2 proteins. This mutation was also found in the girl's father. LT4 treatment was started, resulting in a marked improvement of her hypotonia, motor skills, and growth. Functionally, the missense mutation led to decreased transcriptional activity of TRα1, whic...Continue Reading

References

Sep 1, 1975·The Medical Clinics of North America·H G Fein, R S Rivlin
Dec 18, 1986·Nature·C WeinbergerR M Evans
Aug 3, 1999·The Journal of Clinical Investigation·E D AbelF Wondisford
Jan 26, 2000·Thyroid : Official Journal of the American Thyroid Association·J PohlenzR E Weiss
Jun 9, 2000·Annual Review of Physiology·J Zhang, M A Lazar
Dec 6, 2001·Proceedings of the National Academy of Sciences of the United States of America·M KaneshigeS Cheng
Oct 3, 2002·The EMBO Journal·Alexander TinnikovBjörn Vennström
Apr 30, 2005·Trends in Endocrinology and Metabolism : TEM·Sheue-yann Cheng
Jun 19, 2007·Best Practice & Research. Clinical Endocrinology & Metabolism·Samuel Refetoff, Alexandra M Dumitrescu
Jan 22, 2008·Blood·Tulene S KendrickEvan Ingley
Jan 7, 2010·Endocrine Reviews·Sheue-Yann ChengPaul J Davis
Dec 16, 2011·The New England Journal of Medicine·Elena BochukovaKrishna Chatterjee
Apr 13, 2012·The New England Journal of Medicine·Alies van MullemTheo J Visser
Sep 5, 2012·The Journal of Clinical Investigation·Gregory A Brent
May 2, 2013·The Journal of Clinical Endocrinology and Metabolism·Alies A van MullemRobin P Peeters
Aug 14, 2013·The Journal of Clinical Endocrinology and Metabolism·Carla MoranKrishna Chatterjee
May 23, 2014·European Thyroid Journal·Alies A van MullemRobin P Peeters
Feb 12, 2015·Journal of Medical Genetics·Anna Tylki-SzymańskaKrystyna H Chrzanowska
Aug 26, 2015·Best Practice & Research. Clinical Endocrinology & Metabolism·Carla Moran, Krishna Chatterjee

❮ Previous
Next ❯

Citations

Nov 5, 2016·Thyroid : Official Journal of the American Thyroid Association·Federica MarelliLuca Persani
Nov 18, 2016·The Journal of Endocrinology·Juan Bernal
May 5, 2017·Thyroid : Official Journal of the American Thyroid Association·Carla MoranKrishna Chatterjee
Dec 6, 2017·Thyroid : Official Journal of the American Thyroid Association·Suzy MarkossianFrédéric Flamant
Feb 13, 2019·Hormones : International Journal of Endocrinology and Metabolism·Ozlem KorkmazSukran Darcan
Feb 15, 2019·Thyroid : Official Journal of the American Thyroid Association·Bernard FreudenthalGraham R Williams
Mar 1, 2019·The Journal of Clinical Endocrinology and Metabolism·Karn WejaphikulW Edward Visser
Sep 19, 2019·Thyroid : Official Journal of the American Thyroid Association·Karn WejaphikulMarcel E Meima
May 5, 2016·The Journal of Clinical Endocrinology and Metabolism·Korcan DemirTheo J Visser
Jul 7, 2016·The Journal of Clinical Endocrinology and Metabolism·Carla Moran, Krishna Chatterjee
Sep 16, 2017·The Journal of Clinical Endocrinology and Metabolism·Anja L M van GuchtRobin P Peeters
Jan 25, 2020·Nature Reviews. Endocrinology·Victoria D LeitchGraham R Williams
Aug 31, 2017·Journal of Endocrinological Investigation·G R Williams, J H D Bassett
Mar 8, 2019·Journal of the Endocrine Society·Hui SunLinqi Chen
Aug 9, 2020·Thyroid : Official Journal of the American Thyroid Association·Cho Rong HanSheue-Yann Cheng
Sep 15, 2020·Thyroid : Official Journal of the American Thyroid Association·Yue LiangWeiping Teng
Feb 16, 2021·European Journal of Pediatrics·Peter LaufferNitash Zwaveling-Soonawala
Dec 5, 2020·Endocrinology·Anne H van der SpekAnita Boelen
Jun 3, 2021·International Journal of Molecular Sciences·Sarah PaisdziorMarkus Schuelke

❮ Previous
Next ❯

Methods Mentioned

BETA
X-ray
PCR
transfection
electrophoretic mobility shift assay

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

The Journal of Clinical Endocrinology and Metabolism
Stéphanie EspiardJean-Louis Wémeau
The New England Journal of Medicine
Alies van MullemTheo J Visser
© 2022 Meta ULC. All rights reserved