Ataxia Telangiectasia
Conditions
Brief summary
The goal of this observational study is to identify progressive changes of quantitative brain and lung imaging, serum and movement-related biomarkers reflecting disease progression in pre-symptomatic infants and very young children (0-5 yo) with a genetic diagnosis of A-T, that could be used in future early-life intervention trials.
Interventions
None listed
Sponsors
University of Nottingham
Study design
Observational model
COHORT
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Age
0 Years to 5 Years
Healthy volunteers
Yes
Inclusion criteria
1. Participants with A-T * Inclusion criteria * Genetic diagnosis of Ataxia Telangiectasia * Aged under two years old at the time of first recruitment * Parents/ guardians able to give informed consent *
Exclusion criteria
* Contraindication to MRI * Diagnosis of any other neurogenetic disease * On approved treatment targeting neurodegeneration in A-T at the time of first recruitment * Participating in the trial of novel therapy targeting neurodegeneration in A-T at the time of first recruitment NB - co-recruitment to other observational studies or trials is permitted. If a family chooses to enrol their child in an interventional study targeting neurodegeneration, provided that the intervention trial allows co-recruitment, we would like to retain the participant in the BOBCAT study until its conclusion. In this circumstance, the child's data would not be considered as part of the natural history dataset but would instead be used to demonstrate the feasibility of collecting longitudinal quantitative imaging and other biomarker data in people with A-T during infancy and early childhood. 2. Participants without A-T * Inclusion criteria * Child undergoing general anaesthesia at Nottingham University Hospitals NHS Trust for minor surgical procedures or diagnostic MRI. * Aged 0-5 years (to match the age range of participants with A-T throughout the longitudinal study). * Parents/ guardians able to give informed consent *
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Brain MRI - Volumetric structural T1-weighted (T1) | Up to 4 years ( last visit) | Volume (mm³) - Acquisition parameters aligned to HEALthy Brain and Child Development Study (HBCD) |
| Brain MRI - Magnetic Resonance Spectroscopy (MRS): quantification of N-acetyl aspartate in the cerebellum | Up to 4 years ( last visit) | Chemical shift (ppm) - Acquisition parameters aligned to HEALthy Brain and Child Development Study (HBCD) |
| Brain MRI - Diffusion Weighted Imaging (DWI) | Up to 4 years ( last visit) | Apparent Diffusion Coefficient (mm²/s) - Acquisition parameters aligned to HEALthy Brain and Child Development Study (HBCD) |
| Neurological and developmental assessment | Up to 4 years ( last visit) | * A-TNEST test * Denver Developmental Screening Test II (DDST) |
| Quantitative movement analysis | Up to 4 years ( last visit) | Quantitative analysis of limb, facial and eye movements will be made using a machine learning approach. |
| Serum markers of neurodegeneration | Up to 4 years ( last visit) | * Neurofilament light chain (NFL) * Glial fibrillary acidic protein (GFAP) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Lung MRI | Up to 4 years ( last visit) | • Lung MRI metrics, feasibility, and the results of the quantitative analyses, where it has been possible to do this. * free-breathing proton-based ventilation * structural images using the proton-based techniques |
| Natural sleep MRI procedure | Up to 4 years ( last visit) | Completion rates (%) and image quality (Signal-to-Noise Ratio, SNR, and Contrast-to-Noise Ratio CNR - unitless ) when using the sleep MRI protocol |
Outcome results
None listed