<p>Sjogren-Larsson Syndrome: Mechanisms and Management</p>

Abstract

Sjogren Larsson syndrome (SLS) is a rare autosomal recessive inborn error of lipid metabolism due to mutations in the ALDH3A2 that result in a deficiency of fatty aldehyde dehydrogenase (FALDH). The syndrome has a high prevalence in Sweden where it was first described, but now known to occur worldwide. The classical triad of ichthyosis, mental retardation and spasticity characterizes clinical features. Preterm birth is common. "Glistening white dots" in the retina is a pathognomic clinical feature. Magnetic resonance imaging of the brain demonstrates leukoencephalopathy predominant in the periventricular region. Cerebral MR spectroscopy reveals a characteristic abnormal lipid peak at 1.3ppm and a small peak at 0.9ppm. The primary role of FALDH is oxidation of medium and long-chain aliphatic aldehydes derived from fatty alcohol, phytanic acid, ether glycerolipids and sphingolipids. The diagnosis is based on the typical phenotype, demonstration of the enzyme deficiency and presence of biallelic mutations in the ALDH3A2. The management of SLS largely remains symptomatic currently. However, several potential therapeutic options are being developed, keeping in view of the fundamental metabolic defects or correcting the genetic defect. This review aims to summarize the clinical, genetic and biochemical findings, pathogenetic mechanisms and the current therapeutic options, in SLS.

Sjögren-Larsson syndrome: phenotypic heterogeneity in 3 Moroccan siblings

“…Brain magnetic resonance imaging showed mild to moderate brain atrophy, and delayed myelination/ dysmyelination appearing as diffuse T2 hyperintensity in periventricular and subcortical white matter of both cerebral hemispheres, relatively sparing the subcortical U fibres, or in deep white matter centrum semiovale as was observed in our patient [4].…”

“…Palmoplantar keratoderma may be present and pruritus is usually present. Histopathology of the skin biopsy showed hyperkeratosis with keratotic plugging suggestive of ichthyosis [3,4]. Our first case had similar cutaneous findings however, the two others had ichthyosis predominantly on lower limbs.…”

“…Cognitive development is slow associated with mild to moderate mental retardation. Speech and language problems usually are noted due to both motor and cognitive delays [4,5]. Our three cases had psychomotor and speech delays.…”

“…The affirmative diagnosis will be obtained by DNA sequencing and identifying mutations in the ALDH3A2 gene. This genetic testing is highly sensitive and can complement or even replace FALDH enzymatic assays [4].…”

Sjogren–Larsson Syndrome: A case series of five members from an extended family with a novel mutation

“…The sauna baths and frequent showers help in reducing the pruritic condition of SLS patients. Leukotriene synthesis inhibitors were predicted as curative treatment of the future for the ichthyosis and pruritus of the SLS patients (Bindu, 2020).…”