UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate®

Sjögren-Larsson综合征

Authors
Amy T Waldman, MD
Raphael Schiffmann, MD, MHSc
Section Editors
Francisco González-Scarano, MD
Marc C Patterson, MD, FRACP
Deputy Editor
John F Dashe, MD, PhD
Translators
赵红东, 主任医师，副教授

引言

Sjögren-Larsson综合征(Sjögren-Larsson syndrome, SLS；MIM #270200)是一种常染色体隐性遗传性神经皮肤病，起因于脂肪醇氧化相关机制发生先天性缺陷。1957年，Sjögren和Larsson首次描述了这种疾病，他们报道了一项病例系列研究，涉及的28例患者具有临床三联征：鱼鳞病、痉挛性双瘫或四肢瘫以及智力障碍(精神发育迟滞、精神发育不全)[1]。

本专题将总结SLS的发病机制、临床特征、诊断和处理。

发病机制

SLS是一种由脂肪醛脱氢酶(fatty aldehyde dehydrogenase, FALDH)缺乏导致的脂肪醇代谢障碍(图 1)，FALDH是脂肪醇：烟酰胺腺嘌呤二核苷酸氧化还原酶(fatty alcohol:nicotinamide-adenine dinucleotide oxidoreductase, FAO)酶复合物中的一种成分[2,3]。

FAO由两种独特的蛋白质组成，这两种蛋白质能够按顺序催化脂肪醇氧化成脂肪醛，然后催化脂肪醛氧化成脂肪酸(图 2)[2,3]：

●脂肪醇脱氢酶(fatty alcohol dehydrogenase, FADH)，催化中链和长链脂肪醇氧化成脂肪醛

                  

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: 2017-06 . | This topic last updated: 2016-01-12.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
References
Top
  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. Rizzo WB. Sjögren-Larsson syndrome: explaining the skin-brain connection. Neurology 1999; 52:1307.
  6. 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.
  7. 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.
  8. 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.
  9. van der Knaap MS, Valk J. Sjögren-Larsson Syndrome. In: Magnetic Resonance of Myelination and Myelin Disorders, 3rd, Springer, New York 2005. p.384.
  10. 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.
  11. 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.
  12. 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.
  13. 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.
  14. 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.
  15. Chang C, Yoshida A. Human fatty aldehyde dehydrogenase gene (ALDH10): organization and tissue-dependent expression. Genomics 1997; 40:80.
  16. Rizzo WB. Sjögren-Larsson syndrome: molecular genetics and biochemical pathogenesis of fatty aldehyde dehydrogenase deficiency. Mol Genet Metab 2007; 90:1.
  17. 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.
  18. 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.
  19. Jagell S, Gustavson KH, Holmgren G. Sjögren-Larsson syndrome in Sweden. A clinical, genetic and epidemiological study. Clin Genet 1981; 19:233.
  20. Rizzo WB. Sjögren-Larsson syndrome. http://emedicine.medscape.com/article/949023-overview (Accessed on September 01, 2010).
  21. Jagell S, Heijbel J. Sjögren-Larsson syndrome: physical and neurological features. A survey of 35 patients. Helv Paediatr Acta 1982; 37:519.
  22. Lossos A, Khoury M, Rizzo WB, et al. Phenotypic variability among adult siblings with Sjögren-Larsson syndrome. Arch Neurol 2006; 63:278.
  23. Gordon N. Sjögren-Larsson syndrome. Dev Med Child Neurol 2007; 49:152.
  24. Cubo E, Goetz CG. Dystonia secondary to Sjögren-Larsson syndrome. Neurology 2000; 55:1236.
  25. 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.
  26. Caglayan AO, Gumus H. A very rare neurocutaneous disorder in 2 siblings: Sjögren-Larsson syndrome. J Child Neurol 2010; 25:1003.
  27. McLennan JE, Gilles FH, Robb RM. Neuropathological correlation in Sjögren-Larsson syndrome. Oligophrenia, ichthyosis and spasticity. Brain 1974; 97:693.
  28. Yamaguchi K, Handa T. Sjögren-Larsson syndrome: postmortem brain abnormalities. Pediatr Neurol 1998; 18:338.
  29. 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.
  30. Sjogren-Larsson syndrome. http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/clinical_disease_id/26985?db=genetests (Accessed on September 01, 2010).
  31. Rizzo WB. Sjögren-Larsson syndrome. Semin Dermatol 1993; 12:210.
  32. Rizzo WB, Craft DA, Kelson TL, et al. Prenatal diagnosis of Sjögren-Larsson syndrome using enzymatic methods. Prenat Diagn 1994; 14:577.
  33. Rud E. Et tilfaelde af infantilisme med tetani, epilepsi, polyneuritis, ichthyosis og anaemi of pernicios type. Hospitalstidende 1927; 70:525.
  34. Williams ML, Koch TK, O'Donnell JJ, et al. Ichthyosis and neutral lipid storage disease. Am J Med Genet 1985; 20:711.
  35. Dorfman ML, Hershko C, Eisenberg S, Sagher F. Ichthyosiform dermatosis with systemic lipidosis. Arch Dermatol 1974; 110:261.
  36. Chanarin I, Patel A, Slavin G, et al. Neutral-lipid storage disease: a new disorder of lipid metabolism. Br Med J 1975; 1:553.
  37. 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.
  38. 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.
  39. Kihara H. Genetic heterogeneity in metachromatic leukodystrophy. Am J Hum Genet 1982; 34:171.
  40. Castaño Suárez E, Segurado Rodríguez A, Guerra Tapia A, et al. Ichthyosis: the skin manifestation of multiple sulfatase deficiency. Pediatr Dermatol 1997; 14:369.
  41. Diez-Roux G, Ballabio A. Sulfatases and human disease. Annu Rev Genomics Hum Genet 2005; 6:355.
  42. Haddad FS, Lacour M, Harper JI, Fixsen JA. The orthopaedic presentation and management of Sjögren-Larsson syndrome. J Pediatr Orthop 1999; 19:617.
  43. Haug S, Braun-Falco M. Restoration of fatty aldehyde dehydrogenase deficiency in Sjögren-Larsson syndrome. Gene Ther 2006; 13:1021.
  44. Guilleminault CG, Harpey JP, Lafourcade J. Sjögren-Larsson syndrome. Report of two cases in twins. Neurology 1973; 23:367.
  45. Maaswinkel-Mooij PD, Brouwer OF, Rizzo WB. Unsuccessful dietary treatment of Sjögren-Larsson syndrome. J Pediatr 1994; 124:748.
  46. Willemsen MA, Rotteveel JJ, Steijlen PM, et al. 5-Lipoxygenase inhibition: a new treatment strategy for Sjögren-Larsson syndrome. Neuropediatrics 2000; 31:1.
  47. 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.