# Altered Dopamine Metabolism and Response to Treatment with Levodopa/Carbidopa in MCT8 Deficiency

## TL;DR

This study explores dopamine metabolism and treatment response in a rare brain disorder caused by a gene variant, showing that a common Parkinson's drug helps some patients.

## Contribution

The study demonstrates that levodopa/carbidopa can alleviate movement symptoms in MCT8 deficiency, suggesting a role for dopamine dysfunction in the condition.

## Key findings

- CSF analysis revealed reduced homovanillic acid levels in 3 out of 10 patients with MCT8 deficiency.
- Levodopa/carbidopa treatment improved parkinsonism and reactivity in 7 out of 10 patients.
- Dopaminergic circuit involvement in MCT8 deficiency is confirmed, supporting the use of dopaminergic therapy.

## Abstract

Allan‐Herndon‐Dudley syndrome (AHDS)/monocarboxylate transporter 8 (MCT8) deficiency is a rare X‐linked encephalopathy caused by SLC16A2 variants, impairing thyroid hormone (TH) transport into the brain. This leads to early central nervous system (CNS) TH deficiency, affecting brain maturation. Dopaminergic circuit involvement is suggested by both pathophysiology and clinical features, reminiscent of infantile parkinsonism.

This study investigates dopamine metabolism and levodopa/carbidopa response in MCT8 patients.

We retrospectively and prospectively collected clinical, genetic, and neuroimaging data, performed cerebrospinal fluid (CSF) biogenic amine analyses, and conducted neurological assessments before and after the levodopa trial (10 mg/kg/day).

Ten patients exhibited developmental delay, spasticity, and infantile parkinsonism. CSF analysis showed reduced homovanillic acid in 3/10 patients, with 7/10 in the lowest quartile. Levodopa improved parkinsonism and reactivity in 7/10 patients.

Our findings confirm dopaminergic involvement in AHDS and show that levodopa/carbidopa effectively treats extrapyramidal symptoms. Further investigations could differentiate presynaptic and postsynaptic defects to optimize dopaminergic therapy. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.