Clinical Features of 10 Unrelated Patients With MME Mutations
P1, a 67‐year‐old man born to healthy consanguineous parents, had no relevant medical history. At aged 54 years, he first noticed that his flip‐flops slipped off easily because of foot drop and subsequently developed a slowly progressive gait disturbance and dysesthesia of the lower limbs. Neurological examination revealed severe weakness and atrophy of the distal limb muscles, especially the bilateral tibialis anterior muscles, which was grade 1 on the Medical Research Council scale.26 Superficial and deep sensations were decreased in the lower limbs. The cranial nerves were normal. Nerve conduction studies (NCSs) showed an axonal type of motor and sensory neuropathy: mild slowing of conduction velocity (> 38 m/s) in the median and ulnar nerve, and absent motor and sensory responses in the lower extremities (Table). On the basis of these findings, he was diagnosed with an autosomal recessively inherited axonal form of CMT. He had no obvious cognitive impairment; his MMSE score was 29/30 and his cognitive subscale of the Japanese version of the Alzheimer's disease assessment scale (ADAS‐J‐cog) score was 5/70. His brain MRI was almost normal (Fig 5A), and a PiB‐PET scan did not show a significant amount of amyloid deposition (Fig 5B).
Figure 5  Magnetic resonance imaging and Pittsburgh compound‐B (PiB) positron emission tomography imaging. (A) T2‐weighted images of P1 showing no significant brain atrophy at 67 years of age. (B) PiB standardized uptake value (SUV) images of PiB retention in P1 at 67‐years of age and a 11C‐PiB‐positive Alzheimer's disease patient. Images from P1 show a lack of PiB retention throughout the gray matter and nonspecific PiB retention in the white matter compared with that of the patient with Alzheimer's disease, which shows a high retention of PiB throughout the gray matter. SUVR = standardized uptake value retention.   We summarized the clinical features and electrophysiological findings of all 10 patients in the Table. Mean age of onset of disease was 47.2 years (range, 36–56). Six of them were born to consanguineous parents (Fig 3). Clinically, all patients had slowly progressive weakness and atrophy of distal limb muscles, gait disturbance (but not yet become wheelchair dependent), sensory disturbance of the distal limbs, and decreased or absent tendon reflexes, all of which were the typical CMT phenotype. No patients showed additional neurological findings, such as pyramidal signs, cerebellar ataxia, and other CNS symptoms. NCSs showed an axonal sensorimotor neuropathy in all patients, except for P5 who was electrophysiologically diagnosed with a demyelinating/intermediate form based on delayed median nerve conduction velocities (37.4 m/s). Nine of the patients evaluated had no apparent cognitive impairment as assessed by the MMSE; all scored 26 or higher. The remaining patient had no subjective memory complaints and no clinically apparent cognitive impairment. MRI or CT scans did not show cerebral atrophy in the 5 patients evaluated.