Maap. Willemsen et al., Clinical, biochemical and molecular genetic characteristics of 19 patientswith the Sjogren-Larsson syndrome, BRAIN, 124, 2001, pp. 1426-1437
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.