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Acta Ophthalmol 2019 Mar 29. 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 Apr 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 Dec;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 Feb 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 Jan 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 Apr 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 2017 Mar 15. Epub 2017 Mar 15.

*Harkness Eye Institute, Columbia University Medical Center; and †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.

J Pediatr Neurosci 2016 Jan-Mar;11(1):68-70

Department of Paediatric Neurology, Institute of Social Paediatrics, Stanley Medical College and Hospital, Chennai, Tamil Nadu, India.

Sjogren-Larsson syndrome is an autosomal recessive disorder characterized by defective activity of fatty aldehyde dehydrogenase. It presents as a triad of congenital ichthyosis, spastic diplegia, and mental retardation. The pathology behind this syndrome is the failure of degradation of fatty aldehydes. Read More

BMJ Case Rep 2016 Apr 19;2016:10.1136/bcr-2016-215110. Epub 2016 Apr 19.

Department of Neurology, Bangur Institute of Neurosciences (BIN), IPGMER, Kolkata, West Bengal, India.

Sjögren-Larsson syndrome is a recessively inherited disease caused by a deficiency of fatty aldehyde dehydrogenase with presenting features of congenital ichthyosis, spastic diplegia or tetraplegia, and mental retardation. The basic pathogenic mechanism is deficiency of fatty aldehyde dehydrogenase, which may lead to an accumulation of long-chain fatty alcohols hampering cell membrane integrity, which further disrupts the barrier function of skin and white matter of the brain. MRI of the brain shows diffuse symmetrical white matter hyperintensities on T2-weighted sequences. Read More

J Biol Chem 2016 May 6;291(22):11676-88. Epub 2016 Apr 6.

From the Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan,

The fatty aldehyde dehydrogenase (FALDH) ALDH3A2 is the causative gene of Sjögren Larsson syndrome (SLS). To date, the molecular mechanism underlying the symptoms characterizing SLS has been poorly understood. Using Aldh3a2(-/-) mice, we found here that Aldh3a2 was the major FALDH active in undifferentiated keratinocytes. Read More

J Dermatol 2016 Mar;43(3):252-63

Department of Dermatology, Faculty of Medicine, Kagawa University, Kagawa, Japan.

Among diseases that cause ichthyosis as one of the symptoms, there are some diseases that induce abnormalities in organs other than the skin. Of these, diseases with characteristic signs are regarded as syndromes. Although these syndromes are very rare, Netherton syndrome, Sjögren-Larsson syndrome, Conradi-Hünermann-Happle syndrome, Dorfman-Chanarin syndrome, ichthyosis follicularis, atrichia and photophobia (IFAP) syndrome, and Refsum syndrome have been described in texts as representative ones. Read More

Clin Dermatol 2016 Mar-Apr;34(2):242-75. Epub 2015 Dec 2.

The Vision Center, Children's Hospital Los Angeles; Department of Ophthalmology, Keck School of Medicine, University of Southern California, 4650 Sunset Blvd, MS #88, Los Angeles, CA, 90027.

Genetic skin diseases, or genodermatoses, often have extracutaneous manifestations. Ocular manifestations in particular can have significant clinical implications, like blindness. Other manifestations, such as the corneal opacities that occur in X-linked ichthyosis, are asymptomatic but characteristic of a particular genodermatosis. Read More

Data Brief 2015 Dec 25;5:745-51. Epub 2015 Oct 25.

Departments of Biochemistry and Chemistry, University of Missouri-Columbia, Columbia, MO 65211, United States.

Enzymes of the aldehyde dehydrogenase (ALDH) superfamily catalyze the nicotinamide adenine dinucleotide-dependent oxidation of aldehydes to carboxylic acids. ALDHs are important in detoxification of aldehydes, amino acid metabolism, embryogenesis and development, neurotransmission, oxidative stress, and cancer. Mutations in genes encoding ALDHs cause metabolic disorders, including alcohol flush reaction (ALDH2), Sjögren-Larsson syndrome (ALDH3A2), hyperprolinemia type II (ALDH4A1), γ-hydroxybutyric aciduria (ALDH5A1), methylmalonic aciduria (ALDH6A1), pyridoxine dependent epilepsy (ALDH7A1), and hyperammonemia (ALDH18A1). Read More

Eur J Dermatol 2015 Sep-Oct;25(5):495-6

Clinical Genetics Department.

Chem Biol Interact 2015 Oct 19;240:60-73. Epub 2015 Aug 19.

Department of Biochemistry and Pharmacology, Post-graduation Program in Pharmaceutical Science, Federal University of Piauí, 64.049-550 Teresina, Brazil.

This study aims to review phytol (PYT), through published articles, periodicals, magazines and patents, which were retrieved from the PM, SD, WS, SP; DII, WIPO, CIPO, USPTO and INPI databases. Among the 149 articles and 62 patents, 27.52% articles and 87. Read More

Anat Rec (Hoboken) 2015 Sep 16;298(9):1622-34. Epub 2015 Jul 16.

Department of Biological Sciences, State University of New York, University at Albany, Albany, New York.

Sjögren's syndrome (SS), an autoimmune exocrinopathy, is associated with dysfunction of the secretory salivary gland epithelium, leading to xerostomia. The etiology of SS disease progression is poorly understood as it is typically not diagnosed until late stage. Since mouse models allow the study of disease progression, we investigated the NOD/ShiLtJ mouse to explore temporal changes to the salivary epithelium. Read More

Acta Derm Venereol 2016 Feb;96(2):255-6

Department of Pediatrics, Radboud university medical centre (Radboudumc), PO Box 9101, 6500 HB Nijmegen, The Netherlands.

J Dermatol 2015 Jul 9;42(7):706-9. Epub 2015 Apr 9.

Department of Genetic Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.

Sjögren-Larsson syndrome (SLS) is a neurocutaneous disorder inherited in an autosomal recessive fashion. SLS patients are characterized by lipid metabolism error, primarily leading to cardinal signs of ichthyosis, spasticity and mental retardation. Additional signs include short stature, epilepsy, retinal abnormalities and photophobia. Read More

Ophthalmology 2015 Aug 14;122(8):1730-2. Epub 2015 Mar 14.

Department of Ophthalmology and Visual Science, Stanley M. Truhlsen Eye Institute, Omaha, Nebraska; VA Nebraska-Western Iowa Health Care System, Omaha, Nebraska. Electronic address:

Front Biosci (Landmark Ed) 2015 Jan 1;20:335-76. Epub 2015 Jan 1.

Medical Biotechnology Division, School of Biosciences and Technology, VIT University, Vellore, Tamil Nadu 632014, India.

The aldehyde dehydrogenase gene superfamily comprises of 19 genes and 3 pseudogenes. These superfamily genes play a vital role in the formation of molecules that are involved in life processes, and detoxification of endogenous and exogenous aldehydes. ALDH superfamily genes associated mutations are implicated in various diseases, such as pyridoxine-dependent seizures, gamma-hydroxybutyric aciduria, type II Hyperprolinemia, Sjogren-Larsson syndrome including cancer and Alzheimer's disease. Read More