X-linked Charcot-Marie-Tooth disease type 5 with recurrent weakness after febrile illness.

ABSTRACT

X-linked Charcot-Marie-Tooth disease type 5 (CMTX5) is an X-linked disorder characterized by early-onset sensorineural hearing impairment, peripheral neuropathy, and progressive optic atrophy. It is caused by a loss-of-function mutation in the phosphoribosyl pyrophosphate synthetase 1 gene (PRPS1), which encodes isoform I of phosphoribosyl pyrophosphate synthetase (PRS-I). A decreased activity leads to nonsyndromic sensorineural deafness (DFN2), CMTX5, and Arts syndrome depending upon residual PRS-I activity. Clinical and neurophysiological features of pediatric CMTX5 are poorly defined. We report two male siblings with peripheral neuropathy and prelingual sensorineural hearing loss who carried a novel c.319A>G (p.Ile107Val) PRPS1 missense mutation. They exhibited recurrent episodes of transient proximal muscle weakness, showing Gowers' sign and waddling gait after suffering from febrile illness. This transient weakness has not been previously reported in CMTX5. A patient with Arts syndrome was reported to have transient proximal weakness after febrile illness. The transient weakness presenting in both CMTX5 and Arts syndrome suggests an overlap of signs and a continuous spectrum of PRS-I hypoactivity disease. Children presenting with transient neurological signs should be evaluated for peripheral neuropathy and consider genetic analysis for PRPS1.