ESPE Abstracts

Background: Monocarboxylate-transporter 8 (MCT8) deficiency, also known as Allan-Herndon-Dudley syndrome (AHDS), is associated with severe motoric and intellectual developmental delay. The pathophysiology is characterized by central hypothyroidism (due to transporter defect) and peripheral hyperthyroidism with thyrotoxicosis. There is often an increase in the peripheral T3 values and a decrease in the T4 values. In addition, numerous comorbidities can be held responsible for a reduced life expectancy. However, the peripheral T3 hormone in particular is rarely measured in routine diagnostics. The sole determination of TSH can be insufficient here, as TSH is often normal. Since 2019 there have been studies that have shown that triiodothyroacetic acid (Triac) can alleviate peripheral thyrotoxicosis and perhaps also improve the neurological phenotype.

Case report: We would like to put forward a case of an infant who presented with muscular hypotonia and developmental delay at the age of 5 months. In a first laboratory investigation for the etiological classification of the neurological symptoms, a normal TSH with 5.04 µU/ml (reference 0.73-8.35), a reduced free T4 with 0.6 ng/dl (reference 0.9-2.0) and a significantly increased free T3 of 9.7 pg/ml (reference 2.2-5.8) were found. A targeted genetic test was carried out with the detection of a pathological mutation in the SLC16A2-gen on the chromosome Xq13.2, responsible for AHDS. Except for a somewhat delayed myelination, no morphological abnormalities were found in the MRI. The EEG examination showed a generalized slowing. The clinical examination revealed a lack of head control. After diagnosis, therapy with Triac was started immediately with increasing doses. Drug levels and hormone values were monitored in close cooperation with Erasmus Medical Centre Rotterdam, The Netherlands.

Conclusion: The patient makes slow developmental progress. He still shows a clear dystonic movement disorder and the motor development is clearly behind. Overall, he eats foods himself properly and rarely gags. The further neurological development remains to be observed. With this case report we would like to describe our experience of a very early diagnosis of a patient with an MCT8 deficiency with the greatest potential benefit of early treatment. The typical morphological phenotypic appearances of patients with the AHDS develop over years and are not expedient, especially in the infant phase. The combination of developmental delay and lack of head control (or even just one symptom) should always lead to a measurement of free T3 hormone. In addition, the SLC16A2-gene should always be included in genetic panel-screenings.