Journal Club - Allan Herndon Dudley syndrome: Report of a novel pathogenic variant in MCT8 gene

Deficiency of the thyroid hormone transporter, monocarboxylase tansporter 8 (MCT8) is associated with severe intellectual and motor disabilities as well as high serum T3 concentrations. Clinical diagnosis is often difficult and estimation of thyroid hormones especially free T3 (FT3) concentrations and appropriate genetic studies are necessary.

The case talks about the genetic investigation of a 1-year-old child associated with developmental delays and thyroid hormone functionality revealing single-base pair duplication in exon 1 of MCT8 gene being the responsible cause. This case study is covered in the Journal of Pediatric Endocrinology and Diabetes which is published by Scientific Scholar.

X-linked MCT8 mutations cause Allan-Herndon-Dudley syndrome (AHDS) characterized by severe developmental delay and specific thyroid function abnormality. WES analysis yielded novel hemizygous single-base pair duplication in exon 1 of MCT8 gene, validated by Sanger sequencing. MRI revealed generalized demyelination with poor gray and white matter differentiation and loss of brain volume. Indirect markers revealed thyrotoxicosis in some peripheral tissues.

Possible benefit of including FT3 assay in addition to TSH and FT4 while evaluating male infants and children with severe developmental delay of unknown etiology enabling timely diagnosis, plausible treatment, and requisite genetic counseling.

The current TSH alone based neonatal screening tests fail to identify these patients though the extremely rare prevalence of this condition may not substantiate the case for including FT3 assay as a part of routine neonatal screening.

Reference:

Kulkarni A, Desai DR, Kothari PN. Allan-Herndon-Dudley syndrome: Report of a novel pathogenic variant in MCT8 gene. J Pediatr Endocrinol Diabetes 2022;2:78-80.