Allan-Herndon-Dudley Syndrome

The goal of this program is to provide expanded access (i.e., before marketing authorization) to tiratricol as treatment for patients with monocarboxylate transporter 8 deficiency (MCT8 deficiency, also known as Allan-Herndon-Dudley syndrome \[AHDS\]), who in their Treating Physician's opinion, could benefit from tiratricol and meet the eligibility criteria.

The Myelin Disorders Biorepository Project (MDBP) seeks to collect and analyze clinical data and biological samples from leukodystrophy patients worldwide to support ongoing and future research projects. The MDBP is one of the world's largest leukodystrophy biorepositories, having enrolled nearly 2,000 affected individuals since it was launched over a decade ago. Researchers working in the biorepository hope to use these materials to uncover new genetic etiologies for various leukodystrophies, develop biomarkers for use in future clinical trials, and better understand the natural history of these disorders. The knowledge gained from these efforts may help improve the diagnostic tools and treatment options available to patients in the future.

Thyroid hormones (TH) play a pivotal role in the development and function of the mammalian brain. Patients with impaired thyroid hormone transport into the brain tissue or in the case of defective local thyroid hormone receptor (collectively referred to as thyroid hormone resistance) subsequently experience psychomotor disabilities. The "DEEPTYPE" registry has been established with the objective of intensifying the genotyping and, in particular, the neurological phenotyping of patients exhibiting deficiencies in either the thyroid hormone transporter (MCT8) or the thyroid hormone receptor alpha (THRα). The objective of this registry-based study is to enhance the diagnostic yield for MCT8 and THRα deficiencies by employing the serum fT3/fT4 ratio as a more sophisticated screening parameter. Furthermore, the investigators will study the genomic regulation of both genes and attempt to identify further coding and non-coding mutations that result in TH resistance. The patient registry "DEEPTYPE" will document the retrospective and prospective clinical data of identified children in a comprehensive manner. This will enable the identification of three key groups: (i) patients with non-coding mutations, (ii) patients with milder phenotypes presenting only with a subset of symptoms seen in both "classic" conditions, and (iii) patients who are ready for clinical trials.

Introduction Rare complex syndromes Patients with complex genetic syndromes, by definition, have combined medical problems affecting multiple organ systems, and intellectual disability is often part of the syndrome. During childhood, patients with rare genetic syndromes receive multidisciplinary and specialized medical care; they usually receive medical care from 3-4 medical specialists. Increased life expectancy Although many genetic syndromes used to cause premature death, improvement of medical care has improved life expectancy. More and more patients are now reaching adult age, and the complexity of the syndrome persists into adulthood. However, until recently, multidisciplinary care was not available for adults with rare genetic syndromes. Ideally, active and well-coordinated health management is provided to prevent, detect, and treat comorbidities that are part of the syndrome. However, after transition from pediatric to adult medical care, patients and their parents often report fragmented poor quality care instead of adequate and integrated health management. Therefore, pediatricians express the urgent need for adequate, multidisciplinary adult follow up of their pediatric patients with rare genetic syndromes. Medical guidelines for adults not exist and the literature on health problems in these adults is scarce. Although there is a clear explanation for the absence of adult guidelines (i.e. the fact that in the past patients with rare genetic syndromes often died before reaching adult age), there is an urgent need for an overview of medical issues at adult age, for 'best practice' and, if possible, for medical guidelines. The aim of this study is to get an overview of medical needs of adults with rare genetic syndromes, including: 1. comorbidities 2. medical and their impact on quality of life 3. medication use 4. the need for adaption of medication dose according to each syndrome Methods and Results This is a retrospective file study. Analysis will be performed using SPSS version 23 and R version 3.6.0.