The physiological actions of thyroid hormone (TH) are mediated through TH alpha and TH beta receptors. Resistance to TH (RTH) is characterized by a lack of peripheral tissues’ response to the active form of TH. TH receptor beta has been extensively studied. Mutations in this receptor were considered the main reason for TH resistance for some time up until the discovery of mutations in TH receptor alpha (TRα) that has attained more focus and interest in recent years. A 13-year-old child with classic hypothyroidism features (coarse facies, growth and developmental delay, skeletal dysplasia, generalized muscular hypertrophy, and severe constipation) associated with near-normal thyroid hormone levels, which did not support the diagnosis of hypothyroidism biochemically. Therefore, progressing with whole-exome sequencing had revealed a de novo heterozygous mutation in a gene encoding TRα that establishes a diagnosis of RTHα. This case report demonstrates a rare form of TH resistance due to mutation of TRα. It also emphasizes that THs act through distinctive receptor subtypes in different target tissues. Moreover, this report aims to raise awareness about this genetic mutation, which is thought to be more common than expected. However, due to its subtle features and insidious presentation, many cases remain undiagnosed; hence, the disorder’s exact incidence is unknown.
De novo mutation loci and clinical analysis in a child with sodium taurocholate cotransport polypeptide deficiency: A case report
