Abstract
Loss-of-function mutations of the PAX8 gene are considered to mainly cause congenital hypothyroidism (CH) due to thyroid hypoplasia. However, some patients with PAX8 mutation have demonstrated a normal-sized thyroid gland. Here we report a CH patient caused by a PAX8 mutation, which manifested as iodide transport defect (ITD). Hypothyroidism was detected by neonatal screening and L-thyroxine replacement was started immediately. Although 123I scintigraphy at 5 years of age showed that the thyroid gland was in the normal position and of small size, his iodide trapping was low. The ratio of the saliva/plasma radioactive iodide was low. He did not have goiter; however laboratory findings suggested that he had partial ITD. Gene analyses showed that the sodium/iodide symporter (NIS) gene was normal; instead, a mutation in the PAX8 gene causing R31H substitution was identified. The present report demonstrates that individuals with defective PAX8 can have partial ITD, and thus genetic analysis is useful for differential diagnosis.
Highlights
Congenital hypothyroidism (CH) is the most common congenital endocrine disorder and occurs at rate of 1 in 3000–4000 births [1]
Upon analysis of the PAX8 gene, we identified the patient washeterozygous for an arginine (CGC)-to-histidine (CAC) substitution at codon 31 (R31H), which was previously reported in a patient with CH [6] (Figure 1)
We reported a Japanese patient with R31H substitution in the PAX8 protein
Summary
Congenital hypothyroidism (CH) is the most common congenital endocrine disorder and occurs at rate of 1 in 3000–4000 births [1]. Diagnostic criteria for ITD include a variable degree of CH and goiter, low or absent radioiodide uptake, as determined by thyroid scintigraphy, and low iodide saliva to plasma (S/P) ratio [13, 14]. This disease is caused by mutations of the NIS gene [13,14,15,16,17]. The PAX8 mutation in this patient manifested as CH due to ITD
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