Most patients with Sjögren-Larsson syndrome (SLS) usually present within the first few years after birth. However, there is no correlation between disease severity and increasing age in adults . In addition, studies have demonstrated phenotypic heterogeneity occurring even within affected families, with some children manifesting a less severe form of the disease .
The usual clinical spectrum consists of cutaneous, neurological and ocular symptoms . The severity of the dermatological features is in not related to the neurological symptomatology.
Patients usually present with skin manifestations as the earliest form of the disease, with skin erythema dominating at birth. The lack of keratinization leaves the skin dry and scaly, with a brown-to-yellow discoloration. The most common sites involved are usually the flexor aspects of the extremities, neck, umbilicus and axilla, with the face being largely unaffected. Pruritus is almost always present in patients with SLS .
Neurological symptoms present as motor deficits in the first 2 years of life, with the legs being more commonly involved than the arms . The spasticity may lead to the development of joint contractures. Patients, though being able to walk, are quickly wheelchair-bound in adolescence.
A delay in developmental milestones and mental retardation characterize the cognitive deficits found in SLS. Acquired skills are usually intact in these patients. The motor and cognitive deficits may contribute to speech abnormalities in these patients, with pseudobulbar dysarthria seen as a significant finding .
SLS may be missed in early infancy or childhood, owing to the occult nature and diminished severity of clinical features.
The definitive diagnosis of SLS is made by the demonstration of reduced activity of fatty aldehyde dehydrogenase (FALDH) (less than 15% of normal value) in skin fibroblasts or white blood cells .
In addition, mutations in the ALDH3A2 gene (that codes for FALDH) may be detected via genetic analyses. Amniocentesis or chorionic villus sampling may help in prenatal diagnosis by demonstrating reduced activity of FALDH in amniocytes and cultured chorionic villi cells respectively .
Delayed myelination may be diagnosed by magnetic resonance imaging (MRI) in patients with SLS, usually presenting as hyperintensities in the periventricular areas on T2-weighted images . Magnetic resonance spectroscopy (MRS) may be useful to show high lipid densities in the white matter around the ventricles. Gliosis is another significant finding seen on MRS .
Gross examination of brain sections shows diffuse atrophy with gliosis, without any significant axonal loss. The lack of myelin may be seen in the cerebral and cerebellar white matter regions .
Lipid deposits may also be seen on microscopy in subpial and subependymal glial cell layers, with the brainstem being involved in a few cases. Breakdown products of lipids (in the form of lipofuscin-laden macrophages) and astrocytes (in the form of ellipsoid bodies) are usually seen in SLS. Axonal injury, represented by spheroid bodies, are also noted to occur .