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Abstract: FR-PO799

Antenatal Membranous Nephropathy and Axonal Charcot-Marie-Tooth Type 2 with c.466delC Mutation in the Metallo-Membrane Endopeptidase Gene: A Warning Signal About Long-Term Use of Neprilysin Inhibitors

Session Information

Category: Genetic Diseases of the Kidneys

  • 1002 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Nortier, Joelle L., Hospital Erasme, Brussels, Belgium
  • Remiche, Gauthier, Erasme, Université Libre de Bruxelles, Brussels, Belgium
  • Dupuis, Michel, Sint Peter Clinic, Ottignies, Belgium
  • Debiec, Hanna, Tenon Hospital, Paris, France
  • Ronco, Pierre M., Hospital Tenon, Paris, France

Group or Team Name

  • Agnès
Background

First cases of truncating mutations in the neprilysin/metallo-membrane endopeptidase (MME) gene were identified in 2002 as the cause of alloimmunization during pregnancy, resulting in moderate to severe forms of antenatal membranous nephropathy (MN). Ten years later, two sisters and one brother of the originally reported Moroccan family, found homozygous for the c.466delC mutation in the MME gene, developed rapid motor and sensory neurological disorders, leading to the diagnosis of axonal Charcot-Marie-Tooth (CMT2). We report here the description of clinical and electrophysiologic investigations.

Methods

Clinical features and ancillary test results were collected from laboratory database and patient charts. Electrodiagnostic tests were carried out by standard techniques with surface electrode recording.

Results

Patient 1 had experienced antenatal MN during her second pregnancy at the age of 23 years. She presented with vasomotor painful episodes and progressive muscle weakness of the lower limbs at the age of 33 years. Two years later, she developed progressive gait disturbances, distal lower limb weakness with foot drop and frequent falls. This was improved by foot orthotics. Neurological examination revealed moderate muscle atrophy of the 4 limbs associated with distal sensory loss. Patient 2, her sister, had a prior history of antenatal MN (at the age of 31 years) and autoimmune thrombocytopenic purpura with a long-term corticosteroid treatment. She presented with falls at the age of 44 years and subsequently broke her foot needing osteosynthesis. First neurologic manifestations of Patient 3, their brother, were painful nocturnal cramps at the age of 30 years. All these patients had normal kidney function parameters and exhibited a typical CMT2 phenotype being demonstrated by the clinical picture and electrodiagnostic test results.

Conclusion

This is the first family associating renal and neurological abnormalities linked to MME gene mutation. This observation confirms that neprilysin/MME is involved in peripheral nerve functioning. Neurological surveillance is recommended in prolonged treatment with neprilysin inhibitors.