Samiksha Fouzdar-Jain1,2,3, Donny W Suh1,2,3, William B Rizzo1. 1. Department of Pediatrics and Child Health Research Institute, University of Nebraska Medical Center , Omaha , NE , USA. 2. Children's Hospital & Medical Center , Omaha , NE , USA. 3. Department of Ophthalmology and Visual Science, Stanley M. Truhlsen Eye Institute, University of Nebraska Medical Center , Omaha , NE , USA.
Abstract
Purpose: Sjögren-Larsson Syndrome (SLS) is a rare genetic disorder characterized by a distinctive crystalline maculopathy, congenital ichthyosis, spasticity and intellectual disability. We review the genetic, biochemical and clinical aspects of SLS with a particular focus on the ophthalmologic features of the disease. Methods: Published reports of SLS are combined with clinical experience to provide an overview of this disease. Results: SLS is caused by bi-allelic mutations in ALDH3A2, which codes for fatty aldehyde dehydrogenase, a key enzyme needed for the metabolism of long-chain aliphatic aldehydes and alcohols. SLS patients display perifoveal crystalline inclusions (glistening white dots) that appear in early childhood, vary from sparse to florid and are located in the inner retina. Other findings include retinal thinning, cystic macular degeneration, retinal pigment epithelium atrophy and deficiency of macular pigment. Photophobia is common. Visual evoked potentials are often absent or delayed, whereas electroretinography studies are usually normal. Mild-moderate deficits in visual acuity are common but vision is usually preserved into adulthood. The maculopathy is thought to be due to the accumulation of fatty aldehydes and/or alcohols, which alter membrane function. Defective macular pigment metabolism may also contribute to a unique susceptibility to photo-oxidative damage in the retina.Conclusions: The distinctive retinal phenotype, together with the neurologic and cutaneous symptoms, allows the ophthalmologist to reliably diagnose SLS. Although no effective treatment exists for the ocular symptoms, emerging insight into the pathogenic mechanisms at play in the eye promises to bring effective therapy for SLS in the future.
Purpose: Sjögren-Larsson Syndrome (SLS) is a rare genetic disorder characterized by a distinctive crystalline maculopathy, congenital ichthyosis, spasticity and intellectual disability. We review the genetic, biochemical and clinical aspects of SLS with a particular focus on the ophthalmologic features of the disease. Methods: Published reports of SLS are combined with clinical experience to provide an overview of this disease. Results: SLS is caused by bi-allelic mutations in ALDH3A2, which codes for fatty aldehyde dehydrogenase, a key enzyme needed for the metabolism of long-chain aliphatic aldehydes and alcohols. SLS patients display perifoveal crystalline inclusions (glistening white dots) that appear in early childhood, vary from sparse to florid and are located in the inner retina. Other findings include retinal thinning, cystic macular degeneration, retinal pigment epithelium atrophy and deficiency of macular pigment. Photophobia is common. Visual evoked potentials are often absent or delayed, whereas electroretinography studies are usually normal. Mild-moderate deficits in visual acuity are common but vision is usually preserved into adulthood. The maculopathy is thought to be due to the accumulation of fatty aldehydes and/or alcohols, which alter membrane function. Defective macular pigment metabolism may also contribute to a unique susceptibility to photo-oxidative damage in the retina.Conclusions: The distinctive retinal phenotype, together with the neurologic and cutaneous symptoms, allows the ophthalmologist to reliably diagnose SLS. Although no effective treatment exists for the ocular symptoms, emerging insight into the pathogenic mechanisms at play in the eye promises to bring effective therapy for SLS in the future.
Authors: Shaza N Al-Holou; Edward Siefker; Samiksha Fouzdar-Jain; Donny W Suh; William B Rizzo Journal: Ophthalmic Genet Date: 2020-06-08 Impact factor: 1.803
Authors: Marcellene H Franzen; Michelle M LeRiger; Kaitlyn P Pellegrino; Jane A Kugler; William B Rizzo Journal: Paediatr Anaesth Date: 2020-10-26 Impact factor: 2.556
Authors: Dulce Lima Cunha; Rose Richardson; Dhani Tracey-White; Alessandro Abbouda; Andreas Mitsios; Verena Horneffer-van der Sluis; Panteleimon Takis; Nicholas Owen; Jane Skinner; Ailsa A Welch; Mariya Moosajee Journal: JCI Insight Date: 2021-05-10