Sjogren-Larsson syndrome - Clinical and MRI/MRS findings in FALDH-deficient patients

Objective: To determine the spectrum of clinical and MRI/H-1 MRS features o f patients with fatty aldehyde dehydrogenase (FALDH) deficiency. Background : The Sjogren-Larsson syndrome (SLS) was originally defined as a clinical t riad consisting of ichthyosis, spastic di- or tetraplegia, and mental retar dation, with autosomal recessive inheritance. By now, both the deficiency o f the enzyme FALDH, and the genetic mutations on chromosome 17 responsible for this deficiency, have been identified. SLS, defined by fibroblast FALDH deficiency, seems to be a much broader syndrome. Methods: The clinical fin dings of 11 FALDH-deficient patients of different ages and one patient with the characteristic SLS-like ichthyosis, but without FALDH deficiency, were evaluated in relation to their cerebral MRI, and to H-1 MRS in six patient s. Results: The severity of neurologic symptoms showed considerable variati on. Fundoscopic perifoveal glistening dots and the characteristic SLS-like ichthyosis were present in all patients. Serial MRI findings showed evidenc e of retarded myelination and a variable degree of dysmyelination. 1H MRS s howed an accumulation of free lipids in the periventricular white matter, e ven before the stage of visible dysmyelination. Conclusions: The neurologic consequences of FALDH deficiency show considerable variation. The characte ristic pattern of ichthyosis and retinal degeneration are seen consistently , yet they are not pathognomonic. MRI and H-1 MRS findings suggest an accum ulation of long-chain fatty alcohol intermediates, resulting in retarded my elination and dysmyelination.