title: Slowly progressive d-bifunctional protein deficiency with survival to adulthood diagnosed by whole-exome sequencing.
abstract: d-Bifunctional protein (DBP) deficiency is an autosomal recessive disorder of peroxisomal fatty acid oxidation caused by mutations in HSD17B4. It is typically fatal by the age of two years with symptom onset during the neonatal period, and survival until late childhood is rare. We herein report the case of a patient with DBP deficiency surviving until adulthood, who showed severe sensorineural deafness, disturbances in language acquisition, slowly progressive cerebellar ataxia, and peripheral neuropathy. This patient, in whom findings of prior investigations were nondiagnostic, had been followed up as having an early-onset spinocerebellar degeneration of unknown etiology. Whole-exome sequencing analysis at the age of 36 showed two heterozygous variants in the gene HSD17B4, which encodes DBP in this patient. A panel of peroxisomal investigations showed normal levels of very long chain fatty acids (VLCFAs) in plasma and elevated serum phytanic acid levels. Recently, an increasing number of patients with DBP deficiency surviving until adolescence/adulthood have been reported, in whom abnormalities in the levels of VLCFAs and other peroxisomal metabolites are marginal or nonexistent. Genetic analysis of HSD17B4 should be considered in adult patients with cerebellar ataxia, peripheral neuropathy, and pyramidal signs in addition to sensorineural auditory disturbance since childhood.
authors.affiliation: Department of Neurology, Graduate School of Medicine, The University of Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsukawa
authors.affiliation: Department of Neurology, Graduate School of Medicine, The University of Tokyo, Japan.
authors.forename: Kagari Mano
authors.initials: KM
authors.lastname: Koshi
authors.affiliation: Department of Neurology, Graduate School of Medicine, The University of Tokyo, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Mitsui
authors.affiliation: Department of Neurology, Graduate School of Medicine, The University of Tokyo, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Bannai
authors.affiliation: Department of Neurology, Graduate School of Medicine, The University of Tokyo, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Kawabe
authors.affiliation: Department of Neurology, Graduate School of Medicine, The University of Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ishiura
authors.affiliation: Department of Neurology, Graduate School of Medicine, The University of Tokyo, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Terao
authors.affiliation: Department of Neurology, Graduate School of Medicine, The University of Tokyo, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Shimizu
authors.affiliation: Department of Pediatrics, National Rehabilitation Center for Children With Disabilities, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Murayama
authors.affiliation: Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Yoshimura
authors.affiliation: Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Doi
authors.affiliation: Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Morishita
authors.affiliation: Department of Neurology, Graduate School of Medicine, The University of Tokyo, Japan.
authors.forename: Shoji
authors.initials: S
authors.lastname: Tsuji
authors.affiliation: Department of Neurology, Graduate School of Medicine, The University of Tokyo, Japan; Department of Neurology, International University of Health and Welfare Mita Hospital, Japan. Electronic address: gotoj-tky@umin.ac.jp.
authors.forename: Jun
authors.initials: J
authors.lastname: Goto
mesh_terms: D000328:Adult; D004252:DNA Mutational Analysis; D018450:Disease Progression; D006801:Humans; D008297:Male; D009154:Mutation; D064029:Peroxisomal Multifunctional Protein-2 / Q000097:blood / Q000172:deficiency* / Q000235:genetics*; D011488:Protein Deficiency / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality
chemical_list: D064029:Peroxisomal Multifunctional Protein-2; C104587:HSD17B4 protein, human
keywords: Cerebellar ataxia; HSD17B4; Hearing impairment; Peripheral neuropathy; Whole-exome sequencing; d-Bifunctional protein deficiency