Register for Patients With Thyroid Hormone Resistance.
NCT Number: NCT06566066
Acronym: DEEPTYPE
Status: RECRUITING
Study Type: OBSERVATIONAL
Conditions: Hypothyroidism|Global Developmental Delay|Intellectual Disability|Dystonia|Muscle Hypotonia|Seizures|Allan-Herndon-Dudley Syndrome|Microcephalus
Interventions: OTHER: no intervention
Sponsor: Charite University, Berlin, Germany
Sex: ALL
Age: CHILD, ADULT, OLDER_ADULT
Enrollment: 200
Study Design: Observational Model: |Time Perspective: p
Start Date: 2021-07-01
Completion Date: 2029-07-31
Locations: Charite - Universitaetsmedizin Berlin, Berlin, 13353, Germany

Summary:
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.

Primary Outcome Measures: Description of infant motor and language development, Bayley Scales of Infant and Toddler Development III =\> (Units on a Scale and Sum Score), 5 years|Description of neurological abnormalities, Hammersmith Infant Neurological Examination (HINE) =\> (Units on a Scale and Sum Score), 5 years|Description of motor development, Gross Motor Function Measure (GMFM-88) =\> (Units on a Scale and Sum Score), 5 years
Secondary Outcome Measures: body weight, kilograms, 5 years|body length, centimeters, 5 years|head circumference, centimeters, 5 years|Reponse to therapies (e.g. Triac, DIPTA, levodopa/carbidopa), Recording of responses to standard and experimental therapies, 5 years|T3, microgram per liter, 5 years|T4, microgram per liter, 5 years|fT3, microgram per liter, 5 years|fT4, microgram per liter, 5 years|TSH, mU per litre, 5 years|CSF fT3, microgram per liter, 5 years|CSF fT4, microgram per liter, 5 years|CSF levodopa, micromol/l, 5 years|CSF homovanillic acid (HVA), micromol/l, 5 years|CSF 5-hydroxyindoleacetic acid (5-HIAA), micromol/l, 5 years|Quantification of dystonia, Burke-Fahn-Marsden Dystonia Rating Scale =\> (Units on a Scale and Sum Score), 5 years|Quantification of parkinsonism in children, Parkinsonism Dystonia Scale for Infants and Young Children =\> (Units on a Scale and Sum Score), 5 years|Quanitification of cerebral palys symptomes, Cerebral Palsy Child Health Index of Life with Disabilities =\> (Units on a Scale and Sum Score), 5 years