- Amy T Waldman, MD
Amy T Waldman, MD
- Assistant Professor of Child Neurology
- Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine
- Raphael Schiffmann, MD, MHSc
Raphael Schiffmann, MD, MHSc
- Medical Director of the Institute of Metabolic Disease
- Adjunct Professor of Biomedical Studies
- Baylor University Medical Center
- Section Editors
- Francisco Gonzalez-Scarano, MD
Francisco Gonzalez-Scarano, MD
- Section Editor — Multiple Sclerosis; Neurovirology & NeuroAIDS
- John P. Howe, III, MD, Distinguished Chair in Health Policy
- The University of Texas Health Science Center at San Antonio
- Marc C Patterson, MD, FRACP
Marc C Patterson, MD, FRACP
- Section Editor — Pediatric Neurology
- Professor of Neurology, Pediatrics, and Medical Genetics
- Chair, Division of Child and Adolescent Neurology
- Mayo Clinic College of Medicine
Sjögren-Larsson syndrome (SLS; MIM #270200) is an autosomal recessive neurocutaneous disorder caused by an inborn error of metabolism involving fatty alcohol oxidation. The disorder was first described in 1957 by Sjögren and Larsson, who reported a series of 28 patients with a clinical triad of ichthyosis, spastic diplegia or quadriplegia, and intellectual disability (mental retardation, oligophrenia) .
This topic will review the pathogenesis, clinical features, diagnosis, and management of SLS.
SLS is a disorder of fatty alcohol metabolism (figure 1) caused by a deficiency of the enzyme fatty aldehyde dehydrogenase (FALDH), a component of the fatty alcohol:nicotinamide-adenine dinucleotide oxidoreductase (FAO) enzyme complex [2,3].
●Fatty alcohol dehydrogenase (FADH), which catalyzes the oxidation of medium- and long-chain fatty alcohols to fatty aldehydes
- SJOGREN T, LARSSON T. Oligophrenia in combination with congenital ichthyosis and spastic disorders; a clinical and genetic study. Acta Psychiatr Neurol Scand Suppl 1957; 113:1.
- Rizzo WB, Dammann AL, Craft DA. Sjögren-Larsson syndrome. Impaired fatty alcohol oxidation in cultured fibroblasts due to deficient fatty alcohol:nicotinamide adenine dinucleotide oxidoreductase activity. J Clin Invest 1988; 81:738.
- Rizzo WB, Craft DA. Sjögren-Larsson syndrome. Deficient activity of the fatty aldehyde dehydrogenase component of fatty alcohol:NAD+ oxidoreductase in cultured fibroblasts. J Clin Invest 1991; 88:1643.
- van Domburg PH, Willemsen MA, Rotteveel JJ, et al. Sjögren-Larsson syndrome: clinical and MRI/MRS findings in FALDH-deficient patients. Neurology 1999; 52:1345.
- Rizzo WB. Sjögren-Larsson syndrome: explaining the skin-brain connection. Neurology 1999; 52:1307.
- Rizzo WB, S'Aulis D, Jennings MA, et al. Ichthyosis in Sjögren-Larsson syndrome reflects defective barrier function due to abnormal lamellar body structure and secretion. Arch Dermatol Res 2010; 302:443.
- Willemsen MA, de Jong JG, van Domburg PH, et al. Defective inactivation of leukotriene B4 in patients with Sjögren-Larsson syndrome. J Pediatr 2000; 136:258.
- Willemsen MA, Van Der Graaf M, Van Der Knaap MS, et al. MR imaging and proton MR spectroscopic studies in Sjögren-Larsson syndrome: characterization of the leukoencephalopathy. AJNR Am J Neuroradiol 2004; 25:649.
- van der Knaap MS, Valk J. Sjögren-Larsson Syndrome. In: Magnetic Resonance of Myelination and Myelin Disorders, 3rd, Springer, New York 2005. p.384.
- Willemsen MA, Rotteveel JJ, de Jong JG, et al. Defective metabolism of leukotriene B4 in the Sjögren-Larsson syndrome. J Neurol Sci 2001; 183:61.
- Sutyak J, Austen KF, Soberman RJ. Identification of an aldehyde dehydrogenase in the microsomes of human polymorphonuclear leukocytes that metabolizes 20-aldehyde leukotriene B4. J Biol Chem 1989; 264:14818.
- Pigg M, Jagell S, Sillén A, et al. The Sjögren-Larsson syndrome gene is close to D17S805 as determined by linkage analysis and allelic association. Nat Genet 1994; 8:361.
- De Laurenzi V, Rogers GR, Hamrock DJ, et al. Sjögren-Larsson syndrome is caused by mutations in the fatty aldehyde dehydrogenase gene. Nat Genet 1996; 12:52.
- Rogers GR, Markova NG, De Laurenzi V, et al. Genomic organization and expression of the human fatty aldehyde dehydrogenase gene (FALDH). Genomics 1997; 39:127.
- Chang C, Yoshida A. Human fatty aldehyde dehydrogenase gene (ALDH10): organization and tissue-dependent expression. Genomics 1997; 40:80.
- Rizzo WB. Sjögren-Larsson syndrome: molecular genetics and biochemical pathogenesis of fatty aldehyde dehydrogenase deficiency. Mol Genet Metab 2007; 90:1.
- Willemsen MA, IJlst L, Steijlen PM, et al. Clinical, biochemical and molecular genetic characteristics of 19 patients with the Sjögren-Larsson syndrome. Brain 2001; 124:1426.
- Sillén A, Anton-Lamprecht I, Braun-Quentin C, et al. Spectrum of mutations and sequence variants in the FALDH gene in patients with Sjögren-Larsson syndrome. Hum Mutat 1998; 12:377.
- Jagell S, Gustavson KH, Holmgren G. Sjögren-Larsson syndrome in Sweden. A clinical, genetic and epidemiological study. Clin Genet 1981; 19:233.
- Rizzo WB. Sjögren-Larsson syndrome. http://emedicine.medscape.com/article/949023-overview (Accessed on September 01, 2010).
- Jagell S, Heijbel J. Sjögren-Larsson syndrome: physical and neurological features. A survey of 35 patients. Helv Paediatr Acta 1982; 37:519.
- Lossos A, Khoury M, Rizzo WB, et al. Phenotypic variability among adult siblings with Sjögren-Larsson syndrome. Arch Neurol 2006; 63:278.
- Gordon N. Sjögren-Larsson syndrome. Dev Med Child Neurol 2007; 49:152.
- Cubo E, Goetz CG. Dystonia secondary to Sjögren-Larsson syndrome. Neurology 2000; 55:1236.
- Jagell S, Polland W, Sandgren O. Specific changes in the fundus typical for the Sjögren-Larsson syndrome. An ophthalmological study of 35 patients. Acta Ophthalmol (Copenh) 1980; 58:321.
- Caglayan AO, Gumus H. A very rare neurocutaneous disorder in 2 siblings: Sjögren-Larsson syndrome. J Child Neurol 2010; 25:1003.
- McLennan JE, Gilles FH, Robb RM. Neuropathological correlation in Sjögren-Larsson syndrome. Oligophrenia, ichthyosis and spasticity. Brain 1974; 97:693.
- Yamaguchi K, Handa T. Sjögren-Larsson syndrome: postmortem brain abnormalities. Pediatr Neurol 1998; 18:338.
- Rizzo WB, Carney G, Lin Z. The molecular basis of Sjögren-Larsson syndrome: mutation analysis of the fatty aldehyde dehydrogenase gene. Am J Hum Genet 1999; 65:1547.
- Sjogren-Larsson syndrome. http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/clinical_disease_id/26985?db=genetests (Accessed on September 01, 2010).
- Rizzo WB. Sjögren-Larsson syndrome. Semin Dermatol 1993; 12:210.
- Rizzo WB, Craft DA, Kelson TL, et al. Prenatal diagnosis of Sjögren-Larsson syndrome using enzymatic methods. Prenat Diagn 1994; 14:577.
- Rud E. Et tilfaelde af infantilisme med tetani, epilepsi, polyneuritis, ichthyosis og anaemi of pernicios type. Hospitalstidende 1927; 70:525.
- Williams ML, Koch TK, O'Donnell JJ, et al. Ichthyosis and neutral lipid storage disease. Am J Med Genet 1985; 20:711.
- Dorfman ML, Hershko C, Eisenberg S, Sagher F. Ichthyosiform dermatosis with systemic lipidosis. Arch Dermatol 1974; 110:261.
- Chanarin I, Patel A, Slavin G, et al. Neutral-lipid storage disease: a new disorder of lipid metabolism. Br Med J 1975; 1:553.
- Fischer J, Faure A, Bouadjar B, et al. Two new loci for autosomal recessive ichthyosis on chromosomes 3p21 and 19p12-q12 and evidence for further genetic heterogeneity. Am J Hum Genet 2000; 66:904.
- Lefèvre C, Jobard F, Caux F, et al. Mutations in CGI-58, the gene encoding a new protein of the esterase/lipase/thioesterase subfamily, in Chanarin-Dorfman syndrome. Am J Hum Genet 2001; 69:1002.
- Kihara H. Genetic heterogeneity in metachromatic leukodystrophy. Am J Hum Genet 1982; 34:171.
- Castaño Suárez E, Segurado Rodríguez A, Guerra Tapia A, et al. Ichthyosis: the skin manifestation of multiple sulfatase deficiency. Pediatr Dermatol 1997; 14:369.
- Diez-Roux G, Ballabio A. Sulfatases and human disease. Annu Rev Genomics Hum Genet 2005; 6:355.
- Haddad FS, Lacour M, Harper JI, Fixsen JA. The orthopaedic presentation and management of Sjögren-Larsson syndrome. J Pediatr Orthop 1999; 19:617.
- Haug S, Braun-Falco M. Restoration of fatty aldehyde dehydrogenase deficiency in Sjögren-Larsson syndrome. Gene Ther 2006; 13:1021.
- Guilleminault CG, Harpey JP, Lafourcade J. Sjögren-Larsson syndrome. Report of two cases in twins. Neurology 1973; 23:367.
- Maaswinkel-Mooij PD, Brouwer OF, Rizzo WB. Unsuccessful dietary treatment of Sjögren-Larsson syndrome. J Pediatr 1994; 124:748.
- Willemsen MA, Rotteveel JJ, Steijlen PM, et al. 5-Lipoxygenase inhibition: a new treatment strategy for Sjögren-Larsson syndrome. Neuropediatrics 2000; 31:1.
- Willemsen MA, Lutt MA, Steijlen PM, et al. Clinical and biochemical effects of zileuton in patients with the Sjögren-Larsson syndrome. Eur J Pediatr 2001; 160:711.