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.