Congenital Hypothyroidism in Two Sudanese Families harboring a novel Iodotyrosine deiodinase mutation (IYD R279C)

Background: Congenital hypothyroidism due to defects in iodotyrosine deiodinase have variable phenotypes and can present as hypothyroid or with normal thyroid testing. Methods: Whole exome sequencing was performed in individuals from 2 families originating in different regions of the Sudan. Mass spectrometry of urine and serum iodotyrosines was performed on subjects from both families. Results: A novel iodotyrosine deiodinase (IYD) mutation (c.835C>T; R279C) was identified in individuals from 2 Sudanese families inherited as autosomal recessive. The mutation was identified by multiple in silica analyses to likely be detrimental. Serum and urine monoiodothyrosine and diiodotyrosine were markedly elevated in the homozygous subjects. Conclusion: Measurement of serum and urine diiodotyrosine and monoiodotyrosine was more sensitive than urine iodine or serum thyroid function tests to determine the effect of the IYD mutation.