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J Inherit Metab Dis 2020 Jun 18. Epub 2020 Jun 18.

Department of Pediatric Neurology, Radboud university medical center, Amalia Children's Hospital, Donders Institute for Brain Cognition and Behaviour, Nijmegen, Netherlands.

Sjögren-Larsson syndrome (SLS) is a rare neurometabolic syndrome caused by deficient fatty aldehyde dehydrogenase. Patients exhibit intellectual disability, spastic paraplegia, and ichthyosis. The accumulation of fatty alcohols and fatty aldehydes has been demonstrated in plasma and skin but never in brain. Read More

Ophthalmic Genet 2020 Jun 8:1-5. Epub 2020 Jun 8.

Department of Pediatrics and Child Health Research Institute, University of Nebraska Medical Center , Omaha, NE, USA.

Background: Sjögren-Larsson syndrome (SLS) is a rare genetic neurocutaneous disease caused by mutations in 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. Read More

JIMD Rep 2020 May 25;53(1):61-70. Epub 2020 Mar 25.

Department of Pediatric Neurology Radboud University Medical Center, Amalia Children's Hospital, Donders Institute for Brain Cognition and Behaviour Nijmegen The Netherlands.

Sjögren-Larsson syndrome (SLS) is a rare inborn error of lipid metabolism. The syndrome is caused by mutations in the gene, resulting in a deficiency of fatty aldehyde dehydrogenase. Most patients have a clearly recognizable severe phenotype, with congenital ichthyosis, intellectual disability, and spastic diplegia. Read More

Adv Protein Chem Struct Biol 2020 4;120:349-377. Epub 2020 Feb 4.

Department of Biomedical Sciences, College of Health and Sciences, Qatar University, Doha, Qatar.

Sjögren-Larsson syndrome (SLS) is an autoimmune disorder inherited in an autosomal recessive pattern. To date, 80 missense mutations have been identified in association with the Aldehyde Dehydrogenase 3 Family Member A2 (ALDH3A2) gene causing SLS. Disruption of the function of ALDH3A2 leads to excessive accumulation of fat in the cells, which interferes with the normal function of protective membranes or materials that are necessary for the body to function normally. Read More

Appl Clin Genet 2020 7;13:13-24. Epub 2020 Jan 7.

TY Nelson Department of Neurology and Neurosurgery, Children's Hospital at Westmead, Sydney, NSW, Australia.

Sjogren Larsson syndrome (SLS) is a rare autosomal recessive inborn error of lipid metabolism due to mutations in the that result in a deficiency of fatty aldehyde dehydrogenase (FALDH). The syndrome has a high prevalence in Sweden where it was first described, but now known to occur worldwide. The classical triad of ichthyosis, mental retardation and spasticity characterizes clinical features. Read More

Clin Genet 2020 May 9;97(5):770-778. Epub 2020 Feb 9.

Department of Dermatology, Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Inherited ichthyoses are a heterogeneous group of rare disorders related to over 40 genes. To identify underlying molecular causes in inherited ichthyosis among Chinese and to correlate genotype and phenotype, 35 probands clinically diagnosed inherited ichthyosis, except ichthyosis vulgaris and X-linked ichthyosis, were included in our study. Molecular analysis was performed using next-generation sequencing (NGS) through multi-gene panel testing targeting all ichthyosis-related genes. Read More

Int J Neurosci 2020 Jan 29:1-5. Epub 2020 Jan 29.

Department of Neurology, Affiliated Hospital of Jining Medical University, Jining, Shandong, 272000, China.

Sjögren-Larsson syndrome is a rare, autosomal, recessive neurocutaneous disorder caused by mutations in the gene, which encodes the fatty aldehyde dehydrogenase enzyme. Deficiency in fatty aldehyde dehydrogenase results in an abnormal accumulation of toxic fatty aldehydes in the brain and skin, which cause spasticity, intellectual disability, ichthyosis, and other clinical manifestations. We present the clinical features and mutation analyses of a case of SLS. Read More

J Cosmet Dermatol 2020 Apr 7;19(4):789-798. Epub 2019 Nov 7.

Department of Developmental Pediatrics, The Second Hospital of Jilin University, Changchun, China.

Background/objectives: Sjogren - Larsson syndrome (SLS) is a rare autosomal recessive disease of the mutation ALDH3A2 that identifies a part of fatty acids for fatty aldehyde dehydrogenase: NAD-oxidoreductase enzyme complex. This study aimed to access variant ALDH3A2 gene coded for FALDH and products regulating pathogenic melanogenesis owing to increased oxidative stress and reactive oxygen species resulting in DNA harm in SLS. By turning them into fatty acids, FALDH avoids the accumulation of toxic fatty aldehydes. Read More

Ophthalmic Genet 2019 08 12;40(4):298-308. Epub 2019 Sep 12.

Department of Pediatrics and Child Health Research Institute, University of Nebraska Medical Center , Omaha , NE , USA.

: 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.: Published reports of SLS are combined with clinical experience to provide an overview of this disease. Read More

Arch Dermatol Res 2019 Nov 6;311(9):721-730. Epub 2019 Aug 6.

Clinical Genetics Department, National Research Centre, Cairo, Egypt.

Assessment of ten Egyptian patients with Sjögren-Larsson syndrome (SLS) detected; unusual clinical manifestations, a first report of brain atrophy in SLS, some patients exhibited neither retinal dots nor white matter changes previously reported as essential manifestations. We identified five mutations in ALDH3A2 gene including a novel one and suggest a founder effect. Sjögren-Larsson syndrome is a rare autosomal recessive inborn error of lipid metabolism caused by mutations in the ALDH3A2 gene that codes for fatty aldehyde dehydrogenase and result in a triad of ichthyosis, spasticity, and mental retardation. Read More

J Hum Genet 2019 Sep 5;64(9):859-865. Epub 2019 Jul 5.

Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt.

Sjögren-Larsson syndrome (SLS) is a rare neurocutaneous disorder characterized by congenital ichthyosis, spastic diplegia and intellectual disability. It is an inborn error of lipid metabolism caused by biallelic mutations in the ALDH3A2 gene encoding the fatty aldehyde dehydrogenase that plays a pivotal role in metabolism of long-chain aliphatic aldehydes and alcohols. In this report, we describe the clinical, neuro-radiological and molecular findings of 35 patients with SLS. Read More

Ophthalmol Retina 2019 06 7;3(6):500-509. Epub 2019 Feb 7.

Department of Ophthalmology, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address:

Purpose: To study long-term macular changes by spectral-domain (SD) OCT in patients with Sjögren-Larsson syndrome (SLS).

Design: Retrospective cohort study.

Participants: Twenty-two patients with genetically proven SLS (12 female, 10 male; median age, 21 years; range, 3-47 years) were included in the study. Read More

J Eur Acad Dermatol Venereol 2019 Nov 6;33(11):2095-2100. Epub 2019 May 6.

Department of Dermatology, University Hospitals Leuven, Leuven, Belgium.

Background: From clinical experience, we know that itch is a major concern for many ichthyosis patients. Nonetheless, no previous studies specifically addressed the issue of itch in ichthyosis.

Objective: The objective of this study was to specifically address the burden of itch and all its dimensions in ichthyosis patients. Read More

Acta Ophthalmol 2019 Sep 29;97(6):e877-e886. Epub 2019 Mar 29.

Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

Purpose: To identify the accurate clinical diagnosis of rare syndromic inherited retinal diseases (IRDs) based on the combination of clinical and genetic analyses.

Methods: Four unrelated families with various autosomal recessive syndromic inherited retinal diseases were genetically investigated using whole-exome sequencing (WES).

Results: Two affected subjects in family MOL0760 presented with a distinctive combination of short stature, developmental delay, congenital mental retardation, microcephaly, facial dysmorphism and retinitis pigmentosa (RP). Read More

Neuropediatrics 2019 04 4;50(2):89-95. Epub 2019 Jan 4.

Radboud University Medical Center, Donders Institute for Brain Cognition and Behaviour, Amalia Children's Hospital, Department of Pediatric Neurology, Nijmegen, The Netherlands.

Aim: Sjögren-Larsson syndrome (SLS) is an autosomal recessively inherited neurometabolic disease caused by an enzyme defect in lipid metabolism. Patients suffer from intellectual disability, bilateral spastic paresis, ichthyosis, visual impairment, and photophobia. Knowledge about the meaning of having SLS in daily life is lacking. Read More

Adv Exp Med Biol 2018;1085:181-182

Department of Ophthalmology, Columbia University, Edward S. Harkness Eye Institute, NewYork-Presbyterian Hospital, New York, NY, USA.

Glistening yellow-white crystalline inclusions in foveal and parafoveal areas are almost pathognomonic (Fig. 36.1). Read More

Arch Argent Pediatr 2018 12;116(6):e773-e777

Laboratorio de Bioquímica y Medicina Experimental, Centro Médico Nacional "20 de Noviembre", ISSSTE.

Sjogren-Larsson syndrome is characterized by congenital ichthyosis, mental retardation and spastic diplegia or quadriplegia. The primary defect in this syndrome is mutation of ALDH3A2 gen that codes for the fatty aldehyde dehydrogenase. Deficiency of this enzyme causes an accumulation of fatty alcohols and fatty aldehydes, leading to altered cell-membrane integrity. Read More

Rev Neurol 2018 Nov;67(10):415-416

Hospital Universitario Puerta del Mar, 11009 Cadiz, Espana.

Hum Mutat 2019 02 26;40(2):177-186. Epub 2018 Nov 26.

Division of Human Genetics, Medical University of Innsbruck, Innsbruck, Austria.

The Sjögren-Larsson syndrome (SLS) is a rare autosomal recessive disorder caused by pathogenic variants in the ALDH3A2 gene, which codes for fatty aldehyde dehydrogenase (FALDH). FALDH prevents the accumulation of toxic fatty aldehydes by converting them into fatty acids. Pathogenic ALDH3A2 variants cause symptoms such as ichthyosis, spasticity, intellectual disability, and a wide range of less common clinical features. Read More

Indian Dermatol Online J 2018 Sep-Oct;9(5):338-340

Department of Dermatology, Venereology and Leprosy, Government Medical College, Nagpur, Maharashtra, India.

Ophthalmic Surg Lasers Imaging Retina 2018 09;49(9):e78-e82

Three adult siblings with Sjögren-Larsson syndrome (SLS) demonstrated signs of late-stage SLS maculopathy, including intraretinal crystals, atrophic changes, and lipofuscin deposition. This first report of SLS maculopathy imaged with optical coherence tomography angiography revealed decreased retinal capillary density, vessel dilation, and increased flow voids in the superficial and deep capillary plexuses. [Ophthalmic Surg Lasers Imaging Retina. Read More

BMC Med Genet 2018 08 29;19(1):152. Epub 2018 Aug 29.

Department of Rehabilitation Medicine, CHA Bundang Medical Center, CHA University, 59 Yatap-ro, Bundang-gu, Seongnam, Gyeonggi-do, 13496, Republic of Korea.

Background: Sjogren-Larsson syndrome is a hereditary neurocutaneous syndrome that is non-progressive in nature. Although neuroregression has been reported in seizure-prone preschool children requiring anti-epileptic treatment, teenage-onset dystonia precipitating neurodegeneration without any immediate causal events has yet to be reported.

Case Presentation: We describe a young woman with spastic diplegia and intellectual disability who began to show progressive neurological deterioration from 12 years of age, with the onset of dystonia and tremor. Read More

FASEB J 2019 01 7;33(1):928-941. Epub 2018 Aug 7.

Laboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan; and.

Insulation by myelin lipids is essential to fast action potential conductivity: changes in their quality or amount can cause several neurologic disorders. Sjögren-Larsson syndrome (SLS) is one such disorder, which is caused by mutations in the fatty aldehyde dehydrogenase ALDH3A2. To date, the molecular mechanism underlying SLS pathology has remained unknown. Read More

J Pediatr Neurosci 2018 Jan-Mar;13(1):34-38

Department of Pediatric Neurology, Faculty of Medicine, Cukurova University, Adana, Turkey.

Background: The neuro-ichthyotic diseases are clinically and genetically heterogeneous. The purpose of this study was to evaluate the clinical and neuroradiological findings and to analyze mutation in 15 patients with neuro-ichthyotic diseases.

Materials And Methods: We retrospectively analyzed the records of 15 patients with the diagnosis of neuro-ichthyotic diseases. Read More

Arq Neuropsiquiatr 2018 Apr;76(4):283

Departamento de Neurologia, Hospital das Clínicas, Universidade de São Paulo, São Paulo, SP, Brasil.

Int J Dermatol 2018 Jul 27;57(7):843-848. Epub 2018 Apr 27.

Suna and İnan Kıraç Foundation, Neurodegeneration Research Laboratory (NDAL), Boğaziçi University, Istanbul, Turkey.

Introduction: Sjögren-Larsson syndrome (SLS) is a rare congenital disorder characterized by the triad of ichthyosis, spasticity, and mental retardation. Patients are usually referred to dermatology clinics during infancy. As paraplegia becomes the most debilitating symptom of the disease within a few years, ichthyosis, although a major burden for the patient, takes a back seat. Read More

Clin Case Rep 2018 01 22;6(1):32-36. Epub 2017 Nov 22.

Genomics Research Center Shahid Beheshti University of Medical Sciences TehranIran.

Sjögren-Larsson syndrome (SLS) is a rare type of congenital ichthyosis with neurological problems and intellectual disability. Homozygous mutations in are known to be responsible for this syndrome. Here, we report an Iranian family with congenital SLS bearing a novel two-base-pair deletion within genomic sequence. Read More

Cutis 2017 Dec;100(6):452-455

Department of Dermatology, Venereology, and Leprology, K.J. Somaiya Medical College, Everard Nagar, Sion, Chunabhatti, Mumbai, India.

Sjögren-Larsson syndrome (SLS) is a rare autosomal-recessive neurocutaneous disorder comprising a triad of ichthyosis, mental retardation, and spastic diplegia or quadriplegia. It has rarely been reported in Asian and Indian populations. We report the case of an Indian patient with SLS who presented with the classical clinical triad and demonstrated characteristic findings on magnetic resonance spectroscopy. Read More

Eur J Med Genet 2018 Mar 26;61(3):139-144. Epub 2017 Nov 26.

Department of Pediatrics, UNMC Child Health Research Institute, University of Nebraska Medical Center, Omaha, NE, USA.

Sjögren-Larsson syndrome (SLS) is a rare autosomal recessive disorder characterized by ichthyosis, spasticity and intellectual disability. The disease is caused by mutations in the ALDH3A2 gene that encodes fatty aldehyde dehydrogenase. We describe 7 Iranian SLS patients from 5 unrelated consanguineous families. Read More

Case Rep Pediatr 2017 18;2017:7981750. Epub 2017 Oct 18.

4th Department of Pediatrics, Faculty of Medicine, Aristotle University of Thessaloniki, Papageorgiou General Hospital, Thessaloniki, Greece.

Sjögren-Larsson syndrome is a rare neurocutaneous disorder characterized by ichthyosis, spastic diplegia or tetraplegia, and intellectual disability. Herein, we describe a case of a Greek patient with ichthyosis and spasticity of the legs but with normal intelligence (IQ 95). This syndrome should be suspected when a child presents with ichthyosis and spastic diplegia or tetraplegia, even if intelligence is normal. Read More

Int J Dermatol 2017 Dec;56(12):1406-1413

Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.

Background: Genodermatoses represent genetic anomalies of skin tissues including hair follicles, sebaceous glands, eccrine glands, nails, and teeth. Ten consanguineous families segregating various genodermatosis phenotypes were investigated in the present study.

Methods: Homozygosity mapping, exome, and Sanger sequencing were employed to search for the disease-causing variants in the 10 families. Read More

Ann Lab Med 2018 01;38(1):80-82

Department of Pediatrics, Inje University Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Korea.

J Perinat Med 2018 Jul;46(5):523-529

Department of Pediatric Neurology, Radboud University Medical Center, Donders Institute for Brain Cognition and Behaviour, Nijmegen, TheNetherlands.

Aim: Preterm birth is the world's leading cause of neonatal death. Unfortunately, the pathophysiology of preterm birth remains poorly understood. Sjögren-Larsson syndrome is a rare, neurometabolic disorder caused by a fatty aldehyde dehydrogenase deficiency. Read More

J Lipid Res 2017 08 6;58(8):1648-1660. Epub 2017 Jun 6.

Department of Nutritional Toxicology, Institute of Nutritional Science, University of Potsdam, 14558 Nuthetal, Germany

Sphingosine 1-phosphate (S1P), a bioactive lipid involved in various physiological processes such as cell proliferation and apoptosis, can be irreversibly cleaved by S1P lyase, yielding phosphoethanolamine and (2)-hexadecenal (2HD). The latter metabolite, an α,β-unsaturated fatty aldehyde, may be susceptible to nucleophilic attack by cellular biomolecules. Hence, we studied whether 2HD forms reaction products with GSH and proteins in vitro. Read More

Clin Genet 2018 04 17;93(4):721-730. Epub 2017 Sep 17.

Department of Rehabilitation Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea.

Sjögren-Larsson syndrome (SLS) is caused by an autosomal recessive mutation in ALDH3A2, which encodes the fatty aldehyde dehydrogenase responsible for the metabolism of long-chain aliphatic aldehydes and alcohols. The pathophysiologic accumulation of aldehydes in various organs, including the skin, brain, and eyes, leads to characteristic features of ichthyosis, intellectual disability, spastic di-/quadriplegia, and low visual acuity with photophobia. The severity of the clinical manifestations thereof can vary greatly, although most patients are bound to a wheelchair due to contractures. Read More

Isr Med Assoc J 2016 Oct;18(10):636-638

Department of Pediatric Hematology-Oncology and Bone Marrow Transplantation, Hadassah-Hebrew University Medical Center, Ein Kerem Campus, Jerusalem, Israel.

PLoS One 2017 17;12(4):e0174572. Epub 2017 Apr 17.

Unit of Rheumatology, Department of Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.

Background: Systemic lupus erythematosus (SLE), is a heterogeneous disease which predominantly affects young females (90%). SLE is associated with a shorter life expectancy than in the general population. Standardized mortality ratios (SMR) of 2. Read More

Actas Dermosifiliogr 2017 Jul - Aug;108(6):601-603. Epub 2017 Apr 11.

Department of Dermatology, Hospital Universitario de Canarias, Tenerife, Spain.

Neuropediatrics 2017 06 7;48(3):205-206. Epub 2017 Apr 7.

APHP, Service de Neurologie Pédiatrique et Maladies Métaboliques, Hôpital Robert Debré, Paris, France.

Retin Cases Brief Rep 2019 Summer;13(3):251-254

Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Naples, Florida.

Purpose: To report spectral domain optical coherence tomography and fundus autofluorescence documentation of late stage macular findings associated with Sjogren-Larsson Syndrome in three adult siblings.

Methods: Three adult siblings with Sjogren-Larsson Syndrome underwent ophthalmic examination and imaging.

Results: Crystalline maculopathy and subretinal deposits, presumably lipofuscin accumulation, with macular atrophy were present in varying degrees in all three adult siblings. Read More

J Child Neurol 2017 01 6;32(1):100-103. Epub 2016 Oct 6.

1 Division of Pediatric Neurosurgery, Department of Neurosurgery, NYU Langone Medical Center, NY, USA.

Intrathecal baclofen therapy is widely accepted as a treatment option for patients with severe spasticity. The current treatment of spasticity in patients with Sjögren-Larsson syndrome is largely symptomatic, given that no effective causal therapy treatments are available. We report the outcome of 2 patients with Sjögren-Larsson syndrome who had pump implantation for intrathecal baclofen. Read More

Nat Commun 2017 03 1;8:14610. Epub 2017 Mar 1.

Laboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12-jo, Nishi 6-chome, Kita-ku, Sapporo 060-0812, Japan.

Lipids are the primary components of the skin permeability barrier, which is the body's most powerful defensive mechanism against pathogens. Acylceramide (ω-O-acylceramide) is a specialized lipid essential for skin barrier formation. Here, we identify PNPLA1 as the long-sought gene involved in the final step of acylceramide synthesis, esterification of ω-hydroxyceramide with linoleic acid, by cell-based assays. Read More

Masui 2017 02;66(2):177-179

Sjögren-Larsson syndrome (SLS) is an autosomal recessive disease characterized by a triad of congenital ichthyosis, spastic quadriplegia and mental retardation. An 11-year-old girl (body weight 30 kg) diagnosed as SLS was admitted with Benett fracture of the right thumb. She was monitored with standard protocol. Read More

Neurology 2017 01;88(1):e1-e4

From the Departments of Neurology (M.N., P.S.B., N.G., S.S., P.S.M., A.B.T.), Clinical Neurosciences (S.C.), and Neuro-Imaging and Interventional Radiology (R.D.B.), National Institute of Mental Health and Neurosciences, Bangalore, India.

Muscle Nerve 2017 04 28;55(4):605-608. Epub 2016 Nov 28.

Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, Minnesota, 55905, USA.

Introduction: Sjögren syndrome is thought to be a lymphocyte-driven process. Peripheral nervous system involvement occurs in about 20%-25% of patients. A sensory-predominant, large-fiber peripheral neuropathy is most common, and it is usually associated with a subacute to chronic presentation. Read More

Acta Ophthalmol 2016 Nov 7;94(7):e663-e664. Epub 2016 Apr 7.

Department of Pediatric Neurology, Radboud University Medical Center, Nijmegen, The Netherlands.

Expert Opin Orphan Drugs 2016 Apr 10;4(4):395-406. Epub 2016 Mar 10.

Department of Pediatrics, University of Nebraska Medical Center, Omaha, NE, USA.

Introduction: Sjögren-Larsson syndrome (SLS) is a rare neurocutaneous disease characterized by ichthyosis, spasticity, intellectual disability and a distinctive retinopathy. It is caused by inactivating mutations in , which codes for fatty aldehyde dehydrogenase (FALDH) and results in abnormal metabolism of long-chain aliphatic aldehydes and alcohols. The potential disease mechanisms leading to symptoms include 1) accumulation of toxic fatty aldehydes that form covalent adducts with lipids and membrane proteins; 2) physical disruption of multi-lamellar membranes in skin and brain; 3) abnormal activation of the JNK cell signaling pathway; and 4) defective farnesol metabolism resulting in abnormal PPAR-α dependent gene expression. Read More

Korean J Pediatr 2016 Jun 30;59(6):276-9. Epub 2016 Jun 30.

Department of Genetics and Molecular Biology, Iran University of Medical Sciences, Tehran, Iran.

Sjogren-Larsson syndrome (SLS) is a rare autosomal recessive neurocutaneous disorder with worldwide incidence of 0.4 per 100,000 people. It is characterized by the triad of congenital ichthyosis, spastic diplegia or quadriplegia, and mental retardation. Read More

Pediatr Neurol 2016 Sep 25;62:73-4. Epub 2016 Apr 25.

Division of Neurology, Children's Hospital of Michigan, Detroit, Michigan; Carman and Ann Adams Department of Pediatrics, Children's Hospital of Michigan, Detroit, Michigan; Wayne State University School of Medicine, Detroit, Michigan.