1. To further unravel biochemical abnormalities in SLS patients2. To study neuro-retinal changes over time to learn more about involved neurons and pathomechanism of ophthalmologic abnormalities in SLS patients 3. To study quality of life and daily…
ID
Source
Brief title
Condition
- Chromosomal abnormalities, gene alterations and gene variants
- Retina, choroid and vitreous haemorrhages and vascular disorders
- Lipid metabolism disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
1. Biochemical study
- First we aim to do targeted metabolomics on plasma samples. We aim to
measure chlorinated lipid species and other targeted lipid analyses. For this
targeted metabolomics gas chromatography mass spectrometry will be used. This
laboratory research will take place at the Translational Metabolic Laboratory
(TML) at the Radboudumc Nijmegen, in collaboration with the laboratory of
professor Ford in the United States of America, the PI of the research group
who first described this metabolic route.
- Next to this targeted metabolomics, we also aim to further examine the
abnormal metabolic routes in SLS patients by untargeted metabolomics. Liquid
chromatography in combination with Qtof mass spectrometry will be applied to
the body fluids of SLS patients. Depending on the results of this screening, we
might also use (already stored and cultured) skin fibroblasts for further
research.
2. Ophthalmological tests
With ophthalmologic tests we want to combine normal control appointments with
some extra research to learn more about the structure of the retina and the
abnormalities in the retina. With OCT-A we want to learn more about the
vascularisation of the retina. OCT-A is one of the newest techniques to
visualize the retinal vasculature. This is not been studied in SLS patients
before as far as we know. We will examine all patients and then compare results
with normal population. Goal of this ophthalmologic study is to get better
insight in the ophthalmologic abnormalities, their course over time and the
pathomechanism.
3. Questionnaire
A questionnaire will be sent by email, with questions about daily functioning
and quality of life.
Secondary outcome
Not applicable
Background summary
Sjögren-Larsson Syndrome (SLS) is an autosomal recessive inherited disorder,
with a clinical triad of intellectual disability, spastic di- or tetraplegia
and ichthyosis. This syndrome is caused by a deficient microsomal fatty
aldehyde dehydrogenase (FALDH). FALDH is part of the fatty alchohol
nicotinamide adenine dinucleotide (NAD) oxidoreductase complex (FAO) and
catalyzes oxidation of many different medium- and long-chain fatty aldehydes
into fatty acids. Deficiency results in the accumulation of fatty aldehydes and
fatty alcohols in body fluids and tissues, which is considered the principal
causative mechanism leading to the overall clinical phenotype of SLS. The FALDH
gene, named ALDH3A2, is located on gene 17p11.2, and mutations in this gene
have been identified in SLS patients.
Our research group already did several studies in this patient group. With new
techniques we would like to find out more about the biochemical abnormalities.
Further elucidation of the underlying (biochemical) mechanisms of disease,
especially the identification of affected pathways and involved lipid species,
potentially leads to the development of novel therapeutic strategies. With new
ophthalmologic diagnostic techniques, we aim to get a completer image of
ophthalmologic abnormalities in this group.
Parents were curious about the quality of life and life habits of all patients.
That is why a questionnaire was added to the study. This way we hope to improve
the care for these patients.
Study objective
1. To further unravel biochemical abnormalities in SLS patients
2. To study neuro-retinal changes over time to learn more about involved
neurons and pathomechanism of ophthalmologic abnormalities in SLS patients
3. To study quality of life and daily habits of SLS patients
Study design
Monocenter, interdisciplinary, cross-sectional, observational cohort study
Study burden and risks
Patients have to come to the hospital for one visit. In this visit, several eye
examinations will be done (part of routine care). The ophthalmologist will do a
regular check up as well. After this, a venous blood sample and a urinary
sample will be taken. There are negligible risks in these ophthalmologic
examinations and collecting the blood and urinary samples. There could be some
physical and psychological discomfort, especially with the blood drawing. We
will locally anesthetize the skin with EMLA. Since we combine the examinations
in one session, with only one venous puncture, we hope to minimalize the
burden.
Geert Grooteplein-Zuid 10
Nijmegen 6525 GA
NL
Geert Grooteplein-Zuid 10
Nijmegen 6525 GA
NL
Listed location countries
Age
Inclusion criteria
- genetically confirmed SLS patient
- subject and/or his parents is/are able and willing to sign the Informed consent before screening evaluations
Exclusion criteria
- Not genetically confirmed SLS patient
- Subject and/or his parents is/are not able or willing to sign the Informed Consent before screening evaluations.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| CCMO | NL58544.091.16 |
| OMON | NL-OMON22068 |