Medical Care

Cutaneous symptoms of Sjögren-Larsson syndrome (SLS) require constant attention. For this reason, parents and caregivers often perceive the ichthyosis as the most obvious and time-consuming symptom of Sjögren-Larsson syndrome. The mainstay of therapy for ichthyosis consists of applying topical moisturizing creams and keratolytic agents, such as alpha-hydroxyacid (eg, lactic acid, glycolic acid), salicylic acid, and urea.^[35]Daily water baths help keep the skin hydrated.

Systemic retinoids markedly benefit ichthyosis; however, they are infrequently used in children because of concern about potential adverse effects (eg, growth delay due to epiphyseal closure). Retinoids are usually stored in the body for long periods because of their fat-soluble properties. Newer, short-lived retinoids (eg, acitretin) may circumvent some of the problems associated with tissue storage of the drug; however, experience with these drugs in patients with Sjögren-Larsson syndrome is limited.^{[35, 36]}

Patients with severe pruritus may benefit from treatment with zileuton, which blocks leukotriene B4 synthesis.^[13]Seizures, if recurrent, usually respond to standard anticonvulsant medications.

Experience in treating the spasticity in individuals with Sjögren-Larsson syndrome with baclofen (Lioresal) is not encouraging. Botulinum toxin (Botox®) injections have been used in several patients with Sjögren-Larsson syndrome; however, anecdotal results indicate only a limited favorable response.

Surgical Care

Spasticity in patients with Sjögren-Larsson syndrome is often improved by surgical procedures (eg, tendon lengthening, adductor release, dorsal root rhizotomy).^[14]These procedures may help some patients with Sjögren-Larsson syndrome become ambulatory.

Consultations

Experience indicates that most patients have received consultative attention from multiple subspecialists before Sjögren-Larsson syndrome is initially diagnosed. After Sjögren-Larsson syndrome is diagnosed, continue subspecialty care to promote an optimal outcome.

Consultation with a dermatologist is important in treating the ichthyosis. Most patients with Sjögren-Larsson syndrome respond to topical keratolytic agents and moisturizing creams. Systemic retinoids are effective in treating the ichthyosis.

A child neurologist should take an active role in evaluating and managing neurologic symptoms in all patients with Sjögren-Larsson syndrome. This is particularly important for recommendations concerning drug or surgical intervention for spasticity and anticonvulsant therapy for seizure disorder.

Patients with Sjögren-Larsson syndrome typically benefit from regular physical therapy to maintain ambulation and to prevent contractures from progressing.

Some patients with this disorder may require consultation with a surgeon to treat spasticity and contractures.

Diet

Dietary supplementation with medium-chain triglycerides reportedly helped the ichthyosis in several patients with Sjögren-Larsson syndrome; however, results have been inconsistent.^[7]

No convincing evidence suggests that changes in diet reduce neurologic symptoms.

Activity

Physical activity, particularly ambulation, is impaired in most patients with Sjögren-Larsson syndrome. Including physical therapy in the care of patients with Sjögren-Larsson syndrome is important to prevent or mitigate leg contractures that naturally develop in this disease.

Medication

Sjogren T, Larsson T. Oligophrenia in combination with congenital ichthyosis and spastic disorders. Acta Psychiatr Neurol Scand. 1957. 32:1-113.
Theile U. Sjogren-Larsson syndrome. Oligophrenia-ichthyosis-di-tetraplegia. Humangenetik. 1974. 22:91-118.
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 Mar. 81(3):738-44. [QxMD MEDLINE Link]. [Full Text].
Rizzo WB, Craft DA. Sjogren-Larsson syndrome. Deficient activity of the fatty aldehyde dehydrogenase component of fatty alcohol:NAD+ oxidoreductase in cultured fibroblasts. J Clin Invest. 1991 Nov. 88(5):1643-8. [QxMD MEDLINE Link].
De Laurenzi V, Rogers GR, Hamrock DJ, et al. Sjogren-Larsson syndrome is caused by mutations in the fatty aldehyde dehydrogenase gene. Nat Genet. 1996 Jan. 12(1):52-7. [QxMD MEDLINE Link].
Rizzo WB, Carney G. Sjogren-Larsson syndrome: diversity of mutations and polymorphisms in the fatty aldehyde dehydrogenase gene (ALDH3A2). Hum Mutat. 2005 Jul. 26(1):1-10. [QxMD MEDLINE Link].
Rizzo WB. Sjogren-Larsson syndrome: fatty aldehyde dehydrogenase deficiency. The Metabolic and Molecular Bases of Inherited Disease. 8th ed. New York, NY: McGraw Hill; 2001. Vol 2: 2239-58.
Jagell S, Liden S. Ichthyosis in the Sjogren-Larsson syndrome. Clin Genet. 1982 Apr. 21(4):243-52. [QxMD MEDLINE Link].
Jagell S, Gustavson KH, Holmgren G. Sjogren-Larsson syndrome in Sweden. A clinical, genetic and epidemiological study. Clin Genet. 1981 Apr. 19(4):233-56. [QxMD MEDLINE Link].
Jagell S, Heijbel J. Sjogren-Larsson syndrome: physical and neurological features. A survey of 35 patients. Helv Paediatr Acta. 1982. 37:519-530.
Willemsen MA, Cruysberg JR, Rotteveel JJ, et al. Juvenile macular dystrophy associated with deficient activity of fatty aldehyde dehydrogenase in Sjogren-Larsson syndrome. Am J Ophthalmol. 2000 Dec. 130(6):782-9. [QxMD MEDLINE Link].
Willemsen MA, Van Der Graaf M, Van Der Knaap MS, et al. MR imaging and proton MR spectroscopic studies in Sjogren-Larsson syndrome: characterization of the leukoencephalopathy. AJNR Am J Neuroradiol. 2004 Apr. 25(4):649-57. [QxMD MEDLINE Link].
Willemsen MA, Lutt MA, Steijlen PM, et al. Clinical and biochemical effects of zileuton in patients with the Sjogren-Larsson syndrome. Eur J Pediatr. 2001 Dec. 160(12):711-7. [QxMD MEDLINE Link].
Haddad FS, Lacour M, Harper JI, Fixsen JA. The orthopaedic presentation and management of Sjogren-Larsson syndrome. J Pediatr Orthop. 1999 Sep-Oct. 19(5):617-9. [QxMD MEDLINE Link].
Cho KH, Shim SH, Kim M. Clinical, biochemical, and genetic aspects of Sjögren-Larsson syndrome. Clin Genet. 2018 Apr. 93 (4):721-730. [QxMD MEDLINE Link].
Rizzo WB. Sjogren-Larsson syndrome: molecular genetics and biochemical pathogenesis of fatty aldehyde dehydrogenase deficiency. Mol Genet Metab. 2007 Jan. 90(1):1-9. [QxMD MEDLINE Link].
Verhoeven NM, Jakobs C, Carney G, Somers MP, Wanders RJ, Rizzo WB. Involvement of microsomal fatty aldehyde dehydrogenase in the alpha-oxidation of phytanic acid. FEBS Lett. 1998 Jun 16. 429(3):225-8. [QxMD MEDLINE Link].
van den Brink DM, van Miert JN, Dacremont G, et al. Identification of fatty aldehyde dehydrogenase in the breakdown of phytol to phytanic acid. Mol Genet Metab. 2004 May. 82(1):33-7. [QxMD MEDLINE Link].
Rizzo WB, Heinz E, Simon M, Craft DA. Microsomal fatty aldehyde dehydrogenase catalyzes the oxidation of aliphatic aldehyde derived from ether glycerolipid catabolism: implications for Sjogren-Larsson syndrome. Biochim Biophys Acta. 2000 Dec 15. 1535(1):1-9. [QxMD MEDLINE Link].
Willemsen MA, Rotteveel JJ, de Jong JG, et al. Defective metabolism of leukotriene B4 in the Sjogren-Larsson syndrome. J Neurol Sci. 2001 Jan 15. 183(1):61-7. [QxMD MEDLINE Link].
Rizzo WB, Craft DA. Sjogren-Larsson syndrome: accumulation of free fatty alcohols in cultured fibroblasts and plasma. J Lipid Res. 2000 Jul. 41(7):1077-81. [QxMD MEDLINE Link].
Rizzo WB, Craft DA, Somer T, et al. Abnormal fatty alcohol metabolism in cultured keratinocytes from patients with Sjogren-Larsson syndrome. J Lipid Res. 2008 Feb. 49(2):410-9. [QxMD MEDLINE Link].
Rizzo WB, S'aulis D, Jennings MA, Crumrine DA, Williams ML, Elias PM. Ichthyosis in Sjögren-Larsson syndrome reflects defective barrier function due to abnormal lamellar body structure and secretion. Arch Dermatol Res. 2010 Jan 5. [QxMD MEDLINE Link].
Arai A, Takeichi T, Wakamoto H, et al. Ceramide profiling of stratum corneum in Sjögren-Larsson syndrome. J Dermatol Sci. 2022 Sep. 107 (3):114-22. [QxMD MEDLINE Link].
James PF, Zoeller RA. Isolation of animal cell mutants defective in long-chain fatty aldehyde dehydrogenase. Sensitivity to fatty aldehydes and Schiff's base modification of phospholipids: implications for Sj-ogren-Larsson syndrome. J Biol Chem. 1997 Sep 19. 272(38):23532-9. [QxMD MEDLINE Link].
van der Veen RL, Fuijkschot J, Willemsen MA, Cruysberg JR, Berendschot TT, Theelen T. Patients with Sjögren-Larsson syndrome lack macular pigment. Ophthalmology. 2010 May. 117(5):966-71. [QxMD MEDLINE Link].
Willemsen MA, Rotteveel JJ, van Domburg PH, et al. Preterm birth in Sjogren-Larsson syndrome. Neuropediatrics. 1999 Dec. 30(6):325-7. [QxMD MEDLINE Link].
Roy U, Das U, Pandit A, Debnath A. Sjögren-Larsson syndrome: a rare disease of the skin and central nervous system. BMJ Case Rep. 2016 Apr 19. 2016:10.1136/bcr-2016-215110. [QxMD MEDLINE Link].
Lossos A, Khoury M, Rizzo WB, et al. Phenotypic variability among adult siblings with Sjogren-Larsson syndrome. Arch Neurol. 2006 Feb. 63(2):278-80. [QxMD MEDLINE Link].
Fuijkschot J, Maassen B, Gorter JW, Gerven M, Willemsen M. Speech-language performance in Sjogren-Larsson syndrome. Dev Neurorehabil. 2009 Apr. 12(2):106-12. [QxMD MEDLINE Link].
Kariminejad A, Barzgar M, Bozorgmehr B, et al. Novel mutations and a severe neurological phenotype in Sjögren-Larsson syndrome patients from Iran. Eur J Med Genet. 2018 Mar. 61 (3):139-44. [QxMD MEDLINE Link].
Willemsen MA, IjLst L, Steijlen PM, et al. Clinical, biochemical and molecular genetic characteristics of 19 patients with the Sjogren-Larsson syndrome. Brain. 2001. 124:1426-1437.
Fuijkschot J, Cruysberg JR, Willemsen MA, Keunen JE, Theelen T. Subclinical changes in the juvenile crystalline macular dystrophy in Sjögren-Larsson syndrome detected by optical coherence tomography. Ophthalmology. 2008 May. 115(5):870-5. [QxMD MEDLINE Link].
Sakai K, Akiyama M, Watanabe T, et al. Novel ALDH3A2 heterozygous mutations in a Japanese family with Sjogren-Larsson syndrome. J Invest Dermatol. 2006 Nov. 126(11):2545-7. [QxMD MEDLINE Link].
Ganemo A, Jagell S, Vahlquist A. Sjogren-larsson syndrome: a study of clinical symptoms and dermatological treatment in 34 Swedish patients. Acta Derm Venereol. 2009. 89(1):68-73. [QxMD MEDLINE Link].
Lacour M, Mehta-Nikhar B, Atherton DJ, Harper JI. An appraisal of acitretin therapy in children with inherited disorders of keratinization. Br J Dermatol. 1996 Jun. 134(6):1023-9. [QxMD MEDLINE Link].
Theile U. Sjogren-Larsson syndrome. Oligophrenia--ichthyosis--di-tetraplegia. Humangenetik. 1974 May 17. 22(2):91-118. [QxMD MEDLINE Link].