Macular crystalline inclusions in Sjögren-Larsson syndrome are dynamic structures that undergo remodeling

ABSTRACT

Background

Sjögren-Larsson syndrome (SLS) is a rare genetic neurocutaneous disease caused by mutations in ALDH3A2 that results in deficiency of fatty aldehyde dehydrogenase and accumulation of fatty aldehydes and alcohols. The disease is associated with ichthyosis, spasticity, and intellectual disability. Patients exhibit a characteristic retinopathy with macular crystalline inclusions that first appear in early childhood and increase with age. Once formed, the inclusions are thought to be inert and irreversible. We sought to document how the crystalline inclusions change over time.

Materials and Methods

Serial retinal photographs of 4 SLS subjects (9–23 years old) were taken over a period of 1–3 years. Images were compared by visual inspection and analyzed using ImageJ/Fiji software to observe changes.

Results

Visual inspection of retinal photographs of SLS subjects taken over time demonstrated distinctive changes in crystalline inclusions. New inclusions were formed and some established inclusions regressed. These changes were conveniently demonstrated with software-based photographic image analysis.

Conclusions

We conclude that macular inclusions in SLS are not simply inert deposits, but are dynamic structures that form over time and are subject to remodeling. This conclusion provides new insight into the interplay between the metabolic defect and retinal pathology in SLS, and raises the potential for new therapeutic approaches to reverse some aspects of the maculopathy.

KEYWORDS:

• Fatty alcohol
• fatty aldehyde
• image analysis
• maculopathy
• ALDH3A2

Acknowledgments

We thank Joel Rivas for expert technical assistance with image acquisition. We gratefully acknowledge funding (grant U54 HD061939) from the Sterol and Isoprenoid Research Consortium of the Rare Disease Clinical Research Network, and from the Eunice Kennedy Shriver National Institutes of Child Health & Human Development and National Center for Advancing Translational Sciences, NIH. Funding was also provided by the Child Health Research Institute of the University of Nebraska Medical Center and Children’s Hospital & Medical Center.

Contributions of authors

Manuscript preparation (SNA. WBR); Data Acquisition and analysis (SNA, SFJ, ES, DWS); Manuscript review and approval (all authors).

Disclosure of interest

The authors report no conflicts of interest in this work. No funding source influenced the study design, data interpretation, or writing of this manuscript.

Additional information

Funding

This work was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development [U54 HD061939]; National Center for Advancing Translational Sciences [U54 HD061939]; Child Health Research Institute at UNMC.