Typical clinical and neuroimaging features in Sjögren-Larsson syndrome

Sjögren-Larsson syndrome is an autosomal recessive disorder characterized by ichthyosis, intellectual disability, spastic paraplegia, macular dystrophy, and leukoencephalopathy. It is caused by mutations in ALDH3A2, which leads to accumulation of long chain fatty alcohols. Herein we report on a 28-year-old man with congenital ichthyosis ([Figure A]) and profound intellectual disability, who is severely spastic and had undergone several orthopedic procedures for correction of deformities. Brain MRI disclosed leukoencephalopathy and cortical atrophy ([Figure B]), while MR spectroscopy allowed identification of peaks assigned to lipids ([Figure C]). Sequencing of ALDH3A2 revealed he is a compound heterozygote for two previously reported splice site mutations: maternally inherited c.798+5G>A, and paternally transmitted c.1108-1G>C. Treatment of Sjögren-Larsson syndrome is symptomatic.[1],[2],[3]

Figure A. Congenital ichthyosis. B. MRI: axial FLAIR image demonstrates diffuse leukoencephalopathy. C. MR spectroscopy, single voxel, echo time = 30 ms, region of interest placed in the parieto-occipital white matter, discloses peaks assigned to lipids in 0.8-0.9 ppm and in 1.3 ppm (arrows), which can be appreciated in the disease. The NAA peak is decreased (signaling neuroaxonal loss or dysfunction) and the mI peak is increased (probably related to gliosis). NAA: N-acetyl aspartate; Cr: creatine; Cho: choline; mI: myo-inositol.

• References

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• 2 Willemsen MAAP, Graaf M, Knaap MS, Heerschap A, Domburg PHMF, Gabreels FJM et al. MR imaging and proton MR spectroscopic studies in Sjogren-Larsson syndrome: characterization of the leukoencephalopathy. AJNR Am. J. Neuroradiol. 2004;25(4):649-57.
• 3 Rizzo W, 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(6):1547-60. https://doi.org/10.1086/302681