Hereditary axonal neuropathy related to MME gene mutation in a family with fetomaternal alloimmune glomerulonephritis.

ABSTRACT

We report a consanguineous family with a homozygous and heterozygous membrane metallo-endopeptidase (MME) mutation (c.467delC) and two clinical conditions fetomaternal alloimmune membranous glomerulopathy (FMG) and hereditary motor and sensory axonal neuropathy. The penetrance of both phenotypes was variable. Some individuals experienced unusually fast neurological degradation. Pain and vasomotor signs were frequent complaints, possibly due to a loss of the neutral endopeptidase (NEP, the MME gene product) function and its subsequent inability to degrade substance P and vasomotor peptides. Electrophysiological and nerve biopsy findings were consistent with predominantly axonal neuropathy. This specific clinical phenotype was attributed to a c.467delC MME gene mutation. Diagnosis of such a mutation is important but can be challenging, due to allele dropout. Heterozygous subjects who had already reached the expected age of disease onset had peripheral neuropathy, but also suffered from additional diseases. Neurologists should advise women of childbearing age with MME mutations to seek pre-pregnancy genetic advice and nephrologists should search for neuropathy in patients with FMG.