MCT8 Deficiency in Two Brothers With a Novel Deletion Mutation in SLC16A2

Monocarboxylate transporter 8 (MCT8) deficiency, also known as Allan-Herndon-Dudley syndrome, is a rare X-linked genetic disorder resulting from pathogenic mutations in the SLC16A2 gene. MCT8 deficiency impacts the transport of thyroid hormone (TH) throughout the body. Symptoms are highly heterogeneous and often include severe neurodevelopmental delay, hypotonia in the limbs and trunk, and low body weight.

This case report describes the diagnostic journey of two brothers born 1 year and 8 months apart to nonconsanguineous parents. Both exhibited severely limited motor development, quadriparesis, and an inability to sit independently or hold their head up. Despite their significant clinical presentations, the diagnoses were delayed: 12 years and 8 months for Case 1 and 8 years and 3 months for Case 2. Genetic testing revealed that both patients carry the same novel SLC16A2 mutation, 960_995del (p.Tyr321_Ala332del). Although they displayed key clinical features of MCT8 deficiency, the TH profile of Case 1 was inconclusive, lacking the characteristic sustained elevation of triiodothyronine (T3) typically associated with MCT8 deficiency.

Findings from this case report highlight the need for greater awareness of this disorder and underscore the clinical heterogeneity of MCT8 deficiency.