Sjögren‐Larsson syndrome

Abstract

Sjögren—Larsson syndrome is a recessively inherited syndrome caused by deficiency of fatty aldehyde dehydrogenase. The most common symptoms and signs are described, especially ichthyosis, spastic diplegia, and severe learning difficulties; but also other less frequent ones. Special investigations include sensory evoked potentials, electromyography, and proton magnetic resonance spectroscopy. Post‐mortem examination shows, in particular, an accumulation of lipid substances in specific regions of the brain. The diagnosis depends on the measurement of fatty aldehyde dehydrogenase in cultured fibroblasts from skin biopsies, and by identifying known mutations by allele‐specific polymerase chain reaction assay. Prenatal diagnosis is possible by using the same technique. The disorder is located on gene 17, and many mutations have been identified. Most mutations are unique to an affected family, but clinical variations may be due to unknown genetic and environmental factors. The deficiency of the enzyme impairs the oxidation of medium and long chain fatty aldehydes, and this may explain the link between the brain and skin disorders. The treatment of affected children needs input from a number of specialists, and their contributions are discussed.

Proteomics Characterization of Mouse Kidney Peroxisomes by Tandem Mass Spectrometry and Protein Correlation Profiling

“…At this point, it is also of great interest to note that mutations in the Aldh3a2 gene cause Sjö gren-Larsson syndrome, an inherited human neurocutaneous disorder characterized by ichthyosis, mental retardation, and spasticity. The pathogenesis of these symptoms is thought to result from abnormal lipid accumulation, defective metabolism of eicosanoids, or the increased formation of aldehyde adducts with lipids and/or proteins (68,69).…”

Thematic review series: Skin Lipids. Pathogenesis of permeability barrier abnormalities in the ichthyoses: inherited disorders of lipid metabolism

“…SLS is a recessively inherited disorder of the brain and skin, attributable to the accumulation of free and esterified long-chain aliphatic alcohols (90) as a result of defective peroxisomal oxidation of long-chain aliphatic alcohols. A variety of mutations in the ALDH3A2 gene, encoding the microsomal enzyme fatty aldehyde dehydrogenase, have been described (91,92). Patients with SLS display a characteristic triad of mental retardation, spastic diplegia or quadradiplegia, and ichthyosis (91,93).…”

SjÖgren-Larsson Syndrome

“…EEG showed a slow background activity, without other abnormalities in a study of 19 children, adolescents and adult patients (Willemsen et al 2001a). No peripheral and spinal sensory conduction disorders or motor conduction velocity abnormalities are commonly observed: in some patients however values outside the reference ranges can be recorded (Gordon 2007, Rizzo 2006 (Mano et al 1999;Miyanomae et al 1995;van Somburg et al 1999;Willemsen et al 2000Willemsen et al , 2001aWillemsen et al , 2004Pirgon et al 2006). MRI shows widespread periventricular low signal on T 1 -weighted images and high signal areas on T 2 -weighting, most prominent around the trigones, mild ventricular enlargement, diffuse brain atrophy and a mildly hypoplastic corpus cal- (Fig.…”

“…Short stature is common owing to a combination of growth delay and leg contractures (Gordon 2007, Rizzo 2006). Other secondary features described in some patients, besides small stature, include kyphosis and dental enamel hypoplasia (Forsberg et al 1983).…”