Clinical, biochemical and molecular genetic characteristics of 19 patientswith the Sjogren-Larsson syndrome

Sjogren-Larsson syndrome (SLS) is an autosomal recessively inherited neuroc utaneous disorder caused by a deficiency of the microsomal enzyme fatty ald ehyde dehydrogenase (FALDH). We report the clinical characteristics and the results of molecular studies in 19 SLS patients. Patients 1-17 show the cl assical triad of severe clinical abnormalities including ichthyosis, mental retardation and spasticity. Most patients were born preterm, and all patie nts exhibit ocular abnormalities and pruritus. Electro-encephalography show s a slow background activity, without other abnormalities. MRI of the brain shows an arrest of myelination, periventricular signal abnormalities of wh ite matter and mild ventricular enlargement. Cerebral H-1-MR spectroscopy r eveals a characteristic, abnormal lipid peak. The degree of white matter ab normality in the MRTs and the height of the lipid peak in H-1-MR spectra do not correlate with the severity of the neurological signs. The clinical pr esentation and the clinical course is strikingly similar in these patients. Patient 18 shows a mild phenotype that essentially contains the same, but less severe, clinical features. Patient 19 exhibits the typical, but very m ild, dermatological and ocular abnormalities, without any clinical neurolog ical involvement. The diagnosis of SLS was confirmed by demonstration of th e enzyme defect in cultured skin fibroblasts. Furthermore, as might be pred icted from the essential role of FALDH in leucotriene B-4 (LTB4) metabolism , elevated urinary concentrations of LTB4 and 20-OH-LTB4 were found in all patients studied. Molecular studies of the FALDH gene revealed eight differ ent mutations, including three new ones: a large 26-base pair deletion (21- 46del), a missense mutation (80C -->T) and an insertion mutation (487-488in sA). The vast majority of SLS patients seem to be severely affected indepen dent of their genotype.