Phenotypic diversity of hereditary sensory and autonomic neuropathy type IE: a case series and review of the literature

Noriyuki Miyaue; Yuki Yamanishi; Satoshi Tada; Rina Ando; Hayato Yabe; Noriko Nishikawa; Masahiro Nagai; Hiroshi Takashima; Masahiro Nomoto

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Phenotypic diversity of hereditary sensory and autonomic neuropathy type IE: a case series and review of the literature

Author: Noriyuki Miyaue ¹ ; Yuki Yamanishi ² ; Satoshi Tada ² ; Rina Ando ² ; Hayato Yabe ³ ; Noriko Nishikawa ⁴ ; Masahiro Nagai ² ; Hiroshi Takashima ⁵ ; Masahiro Nomoto ²
Author Information

1. Department of Neurology and Clinical Pharmacology, Ehime University Graduate School of Medicine, Ehime, Department of Neurology and Clinical Pharmacology, Ehime University Graduate School of Medicine, Ehime
2. Department of Neurology and Clinical Pharmacology, Ehime University Graduate School of Medicine, Ehime
3. Department of Neurology, Saiseikai Matsuyama Hospital, Ehime
4. Department of Neurology and Clinical Pharmacology, Ehime University Graduate School of Medicine, Ehime, Department of Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo
5. Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
Publication Type:Journal Article
Keywords: DNMT1; hereditary sensory and autonomic neuropathy; HSAN IE; phenotypic diversity; psychiatric symptom; orexin
From:Neurology Asia 2019;24(1):15-20
CountryMalaysia
Language:English
Abstract: Objective: DNA methyltransferase 1 (DNMT1) is crucial to maintaining methylation during DNA replication and DNA repair. DNMT1 mutations have been identified in two neurological syndromes, including hereditary sensory and autonomic neuropathy type IE (HSAN IE) with dementia and hearing loss and autosomal dominant cerebellar ataxia, deafness and narcolepsy. It is likely that DNMT1 mutations lead to various symptoms of the central and peripheral nervous system. The aim of this study was to examine the clinical characteristics, especially the initial symptoms, in the cases of DNMT1 mutations. Methods: We investigated the clinical manifestation and examination findings of four cases of HSAN IE from one family with the DNMT1 mutation c.1531Y>C (p.Try511His). Results: All four cases exhibited sensory neuropathy, cerebellar ataxia, and hearing loss, all of which were demonstrated by the audiograms. The initial symptoms of the four cases included hearing loss (n=1), gait disturbance (n=1), and depressive mood (n=2). Depressive symptoms are reported in some cases with HSAN IE, however, there are currently no published reports that describe them as primary symptoms. The CSF orexin level was measured in three cases, revealing normal values in two cases and intermediate values in one case, in which the patient exhibited rapid eye movement (REM) sleep behavior disorder. Conclusion: Our findings suggest that in cases with HSAN IE or the DNMT1 mutation, psychiatric symptoms should be taken into account as one of the initial manifestations of the disease.
Full text:7.2019.my003.pdf