Early-onset CMT1B due to the MPZ mutation c.320A>T associated with collateral inclusion body myopathy and Deafness
Josef Finsterer *
Krankenanstalt Rudolfstiftung, Postfach 20, 1180 Vienna, Austria.
Christine Haberler
Institute of Clinical Neurology, Medical University Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
Michaela Auer-Grumbach
Department of Internal Medicine, Division of Endocrinology and Metabolism, Medical University Graz, Auenbruggerplatz 2, 8036 Graz, Austria.
*Author to whom correspondence should be addressed.
Abstract
Aims: To present the case of a patient with early-onset demyelinating neuropathy due to a MPZ-mutation, associated with deafness and inclusion-body-myopathy.
Methods: Nerve conduction studies, electromyography, muscle biopsy, genetic testing.
Results and Discussion: In a 46yo male with slowly progressive weakness and wasting since childhood initially of the lower and later also of the distal upper-limbs, ptosis, recurrent hyper-CK-emia, and progressive hearing impairment, nerve conduction studies revealed mixed demyelinating and axonal polyneuropathy and electromyography revealed neurogenic motor unit architecture. Nerve biopsy disclosed diffuse loss of myelinated fibers, reduced diameter of non-myelinated fibers, and fibers with hypomyelination and variable internodal myelination. Muscle biopsy revealed classical features of inclusion-body-myopathy. Upon genetic diagnostic work-up the MPZ-mutation c.320A>T, p.Glu107Val was detected. Since his son presented with a similar phenotype, inclusion-body-myopathy was interpreted as secondary to the neuropathy.
Conclusions: CMT1B may show secondary axonal loss and mild clinical manifestations despite early onset. CMT1B may be associated with severe hearing impairment and collateral inclusion-body-myopathy.
Keywords: Hereditary neuropathy, charcot-marie-tooth, sensorimotor polyneuropathy, genetics, myelin protein zero.