MME GENE MUTATION CAUSING SPINOCEREBELLAR ATAXIA AND AXONAL POLYNEUROPATHY: CLINICAL CASE

Introduction: Polyneuropathies (PNP) are sometimes associated with spinocerebellar ataxia (SCA). According to subtype of the SCA, they are axonal or demyelinating.

Purpose: We present a case of a 56-year-old woman with ataxic gait and lower limbs neuropathic pain. Clinical examination showed pectus carinatum, pes cavus, amyotrophy, hypoesthesia and areflexia in the lower limbs. Three years later, patient has developed hypometric saccades and dysarthia suggesting cerebellar syndrome. Similar familial clinical findings allow the diagnosis of a rare inherited neurological pathology: SCA43.

Method: The diagnosis is performed by several electrophysiological examinations, brain MRI and molecular genetic study of the patient and his family (28 family members, including 7 living affected individuals).

Results: Electroneuromyography demonstrate subacute axonal sensorimotor PNP, mostly motor rather than sensitive. Sensory evoked potentials attest sensory attack especially in the lower limbs. Brain MRI shows a cerebellar vermis atrophy. Finally, familial genetic study identifies mutation of the MME gene, which codes for a membrane protein, neprilysin (NEP).

Conclusions: NEP is a membrane metalloendopeptidase expressed in the peripheral and central nervous systems and other tissues. The pathogenesis due to loss-of-function of NEP is still unclear.
In this family, the MME mutation transmitted according to the autosomal dominant mode, is responsible for a phenotype of SCA (SCA43), associated to late-onset axonal sensorimotor polyneuropathy. Two other studies show also a late-onset axonal sensorimotor polyneuropathy, without cerebellar dysfunction, in patients with MME mutation. Interestingly, MME mutation produces different clinical phenotypes.