Atypical peripheral manifestation of abnormal sphingolipid metabolism

Abstract

Objective: Defects in sphingolipid-metabolizing enzymes lead to neurometabolic disorders with highly variable onset and symptoms. We present patients with axonal sensitive and motor polyneuropathy plus episodes of recidivans mononeuropathy where we confirmed two heterozygous mutations: c.551T > C (p.I184T) and c.1082C > G (p.S361*) in SGPL1 gene. That gene encoding the sphingosine 1-phosphate lyase (SPL), which catalyzes the irreversible degradation of sphingosine 1-phosphate (S1P) in the final step of sphingolipid catabolism. Methods: Rutine clinical examination and neurophysiology, neuropathology and laboratory procedures were done. After negative CMT panel and Sanger sequencing, WES method was done. Results: Acute onset of motor distal deficits in two sibs, following with few episodes of mononeuropathies. The neurophysiologicaly findings: axonal sensitive and motor neuropathy. Sural nerve biopsy: signs of active axonal disintegration; CSF: normal; There were no abnormalities in central nervous system, renal, adrenal or other tissues. Conclusion: Phenotype of our patients can mimic and be confused with acquired neuropathy or with hereditary demyelinating neuropathy, because of acute onset and remittent course. The phenotype of our patients is very atypical for Charcot Marie Tooth type 2 and is very atypical for sphingolipidosis diseases. We can suppose that patients whose cells retain traces of residual activity could have an attenuated course with less or no somatic signs.