Sjögren-Larsson Syndrome: clinical and biochemical studies

Rationale: 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.

Objectives:

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


Study design: Monocenter, interdisciplinary, prospectivecross-sectional, observational cohort
study


Study population: Patients with genetically proven Sjögren-Larsson Syndrome in the
Netherlands


Main study parameters/endpoints:

1. With targeted and untargeted metabolomics, we aim to determine which lipids accumulate in
SLS patients.

2. With application of novel non-invasive imaging techniques, combined with normal
ophthalmologic outpatient visits, we aim to learn more about the structure of the retina and the
abnormalities in the retina.

One-off measuring moment where patients come to the ophtalmology policlinic in the Radboud UMC for eye examination. On the same day blood and urine will be collected for metabolic research.

Observational cohort study, ophthalmologic and metabolic studies