Takaki Taniguchi1,2, Masahiro Ando1, Yuji Okamoto1,3, Akiko Yoshimura1, Yujiro Higuchi1, Akihiro Hashiguchi1, Nozomu Matsuda4, Mamoru Yamamoto5, Eisuke Dohi6,7, Makoto Takahashi8, Masanao Yoshino9,10, Taichi Nomura10, Masaaki Matsushima10, Ichiro Yabe10, Yui Sanpei11, Hiroyuki Ishiura12, Jun Mitsui13, Masanori Nakagawa14, Shoji Tsuji13,15, Hiroshi Takashima16. 1. Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan. 2. Department of Neurology, Imakiire General Hospital, Kagoshima, Japan. 3. Department of Physical Therapy, School of Health Sciences, Faculty of Medicine, Kagoshima University, Kagoshima, Japan. 4. Department of Neurology, Fukushima Medical University, Fukushima, Japan. 5. Department of Neurology, University of Toyama, Toyama, Japan. 6. Department of Neurology, Hiroshima Prefectural Hospital, Hiroshima, Japan. 7. Department of Neuroscience of Disease, Brain Research Institute, Niigata University, Niigata, Japan. 8. Department of Neurology, Kanto Central Hospital, Tokyo, Japan. 9. Department of Neurology, Obihiro Kosei Hospital, Hokkaido, Japan. 10. Department of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan. 11. Department of Neurology, Akita University Graduate School of Medicine, Akita, Japan. 12. Department of Neurology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan. 13. Department of Molecular Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. 14. North Medical Center, Kyoto prefectural University of Medicine, Kyoto, Japan. 15. Institute of Medical Genomics, International University of Health and Welfare, Chiba, Japan. 16. Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan. takashima8@gmail.com.
Abstract
BACKGROUND AND AIMS: Some hereditary transthyretin (ATTRv) amyloidosis patients are misdiagnosed as Charcot-Marie-Tooth disease (CMT) at onset. We assess the findings to identify ATTRv amyloidosis among patients with suspected CMT to screen transthyretin gene variants for treatments. METHODS: We assessed clinical, cerebrospinal fluid, and electrophysiological findings by comparing ATTRv amyloidosis patients with suspected CMT (n = 10) and CMT patients (n = 489). RESULTS: The median (interquartile range) age at onset of neurological symptoms was 69 (64.2-70) years in the ATTRv amyloidosis vs 12 (5-37.2) years in CMT group (Mann-Whitney U, p < 0.01). The proportion of patients with initial sensory symptoms was 70% in the ATTRv amyloidosis group vs 7.1% in CMT group (Fisher's exact, p < 0.01). The proportion of patients with histories of suspected chronic inflammatory demyelinating polyneuropathy (CIDP) were 50% in the ATTRv amyloidosis group vs 8.7% in CMT group (Fisher's exact, p < .01). Other measures and outcomes were not different between the two groups. Five of the six patients with ATTRv amyloidosis received treatment and survived. INTERPRETATION: For effective treatments, the transthyretin gene should be screened in patients with suspected CMT with old age at onset of neurological symptoms, initial sensory symptoms, and histories of suspected CIDP.
BACKGROUND AND AIMS: Some hereditary transthyretin (ATTRv) amyloidosis patients are misdiagnosed as Charcot-Marie-Tooth disease (CMT) at onset. We assess the findings to identify ATTRv amyloidosis among patients with suspected CMT to screen transthyretin gene variants for treatments. METHODS: We assessed clinical, cerebrospinal fluid, and electrophysiological findings by comparing ATTRv amyloidosis patients with suspected CMT (n = 10) and CMT patients (n = 489). RESULTS: The median (interquartile range) age at onset of neurological symptoms was 69 (64.2-70) years in the ATTRv amyloidosis vs 12 (5-37.2) years in CMT group (Mann-Whitney U, p < 0.01). The proportion of patients with initial sensory symptoms was 70% in the ATTRv amyloidosis group vs 7.1% in CMT group (Fisher's exact, p < 0.01). The proportion of patients with histories of suspected chronic inflammatory demyelinating polyneuropathy (CIDP) were 50% in the ATTRv amyloidosis group vs 8.7% in CMT group (Fisher's exact, p < .01). Other measures and outcomes were not different between the two groups. Five of the six patients with ATTRv amyloidosis received treatment and survived. INTERPRETATION: For effective treatments, the transthyretin gene should be screened in patients with suspected CMT with old age at onset of neurological symptoms, initial sensory symptoms, and histories of suspected CIDP.