Early Diagnosis and Treatment of an Infant with a Novel Thyroid Hormone Receptor Gene (pC380SfsX9) Mutation

Resistance to thyroid hormone alpha (RTH alpha) is caused by mutations in thyroid hormone receptor alpha (THRA). Little is known about the natural history and treatment of RTH alpha, and diagnosis before the age of 1 year has not been previously reported. A de novo heterozygous THRA mutation (pC380SfsX9) was identified in a 10-month-old female investigated for developmental delay, hypotonia, macrocephaly, and severe constipation. Treatment with levothyroxine was accompanied by an appropriate rise in thyroxine (T4), triiodothyronine (T3), as well as decrease in thyrotropin levels and in the T3/T4 ratio with a trend toward normalization of peripheral markers of thyroid hormone action. THRA pC380SfsX9 results in extreme RTH alpha.