PERIPHERAL HYPERMYELINATING NEUROPATHY ASSOCIATED WITH LAMININ ALFA2 DEFICIENCY

Objective: To assess the aetiological role of the defect of laminin alfa2 in producing a peripheral hypermyielinating neuropathy.

Methods: In two patients with a complex phenotype consisting of both central and peripheral changes we thoroughly studied gastrocnemius muscle and sural nerves biopsies. The specimens were examined both as to morphology and by immunohistochemistry. Immunostaining was performed using monoclonal antibodies agains both fragments of laminin alfa2 chain, C-terminal fragment of 80 KD and N-terminal fragment of 300 KD and against laminin alfa5. Antibodies for the detection of dystrophin, á, â, ã and ä –sarcoglycans and â-dystroglycan were also used. Haplotype analysis was performed to try to asses the gene location as well as the study of the exons of LAMA chain gene.

Results: Besides the better definition of the clinical data, namely the cerebral white matter changes on MRI, the epileptic disorder, the nerve and muscle electrophysiological data, the morphological and immunohistochemistry features of muscle and nerve specimens showed a variable deficiency of laminin alfa2 chain that mostly affected the nerve. The ultrastructural examination of the peripheral nerve showed a paranodular globular aspect due to hypermyelination without any demyelination. Haplotype analysis suggested a linkage to the LAMA2 locus. The analysis of LAMA2 exons is in progress.

Conclusion: Hypermyelinating neuropathies can be due also to a deficiency of laminin alfa2 deficiency. This study suggests to look for more diffusely the laminin alfa2 changes in peripheral nerve pathology.