Central and peripheral nervous system dysfunction in the clinical variation of Salla disease

Objective: To evaluate the degree of possible peripheral nervous system (PN S) involvement in addition to CNS manifestations in Salla disease, a free s ialic acid storage disorder leading to severe mental retardation with a wid e clinical variation. Background: Salla disease is a lysosomal storage diso rder that affects the white matter of the CNS. MRI findings and recent H-1 MRS study results provide evidence for delayed central myelination, but the re is no previous evidence for PNS involvement in this disease. The gene co ding for a presumptive sialic acid transport protein has recently been iden tified, and the first disease-causing mutations have been characterized. Me thods: Nerve conduction studies; evoked potentials to visual (VEP), brainst em auditory (BAEP), and somatosensory stimuli (SEP); and EEG were carried o ut on 22 patients (age range 2 months to 57 years) with biochemically and g enetically confirmed Salla disease. Brain MRI were available on 14 patients . Results: Nerve conduction studies revealed abnormalities in nearly half o f the patients (10/21). The four severely disabled patients and the oldest patient had greatly reduced nerve conduction velocities and prolonged dista l latencies compatible with demyelinating polyneuropathy. In addition, SEP was abnormal in the majority of the patients, but VEP and BAEP in only a fe w cases. PNS involvement was clearly associated with both the phenotypic se verity and MRI findings. Conclusions: The results indicate that dysmyelinat ion in Salla disease occurs not only in the CNS but also in the peripheral nervous system, contributing to the phenotypic variation, which can now be correlated with the molecular basis of the disease.