A male case with CDKL5-associated encephalopathy manifesting transient methylmalonic acidemia

Satoshi Akamine, Yoshito Ishizaki, Yasunari Sakai, Hiroyuki Torisu, Ryoko Fukai, Noriko Miyake, Kazuhiro Okubo, Hiroshi Koga, Masafumi Sanefuji, Ayumi Sakata, Masahiko Kimura, Seiji Yamaguchi, Osamu Sakamoto, Toshiro Hara, Hirotomo Saitsu, Naomichi Matsumoto, Shoichi Ohga

研究成果: ジャーナルへの寄稿記事

3 引用 (Scopus)

抄録

Mutations in the X-linked gene CDKL5 cause early-onset epileptic encephalopathy and severe developmental delay. Because this disorder predominantly affects females, the full clinical spectrum of male patients remains elusive. We herein report a 16-year-old boy, who suffered from intractable seizures 20 days after birth. Serial electroencephalograms detected recurrent focal epileptiform discharges from age 4 months, which evolved to hypsarrhythmia later in infancy. Mass-spectrometric analyses revealed increase in urinary excretion of methylmalonic acid without perturbed concentrations of propionic acid, homocystein and methionine. Whole-exome sequencing identified a de novo, truncating mutation in CDKL5 (NM_003159.2:c.419dupA, p.Asn140Lysfs*8). Targeted sequencing excluded concomitant mutations in methylmalonic academia-associated genes. No methylmalonic acidemia has been reported in children with CDKL5 disorder. Extensive analyses on organic acid metabolism for males with CDKL5 mutations will gain more insight into their biochemical profiles in infancy.

元の言語英語
ページ(範囲)451-454
ページ数4
ジャーナルEuropean Journal of Medical Genetics
61
発行部数8
DOI
出版物ステータス出版済み - 8 1 2018

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Brain Diseases
Mutation
Methylmalonic Acid
Exome
Infantile Spasms
X-Linked Genes
Methionine
Electroencephalography
Seizures
Parturition
Acids
Methylmalonic acidemia
Genes

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

これを引用

A male case with CDKL5-associated encephalopathy manifesting transient methylmalonic acidemia. / Akamine, Satoshi; Ishizaki, Yoshito; Sakai, Yasunari; Torisu, Hiroyuki; Fukai, Ryoko; Miyake, Noriko; Okubo, Kazuhiro; Koga, Hiroshi; Sanefuji, Masafumi; Sakata, Ayumi; Kimura, Masahiko; Yamaguchi, Seiji; Sakamoto, Osamu; Hara, Toshiro; Saitsu, Hirotomo; Matsumoto, Naomichi; Ohga, Shoichi.

:: European Journal of Medical Genetics, 巻 61, 番号 8, 01.08.2018, p. 451-454.

研究成果: ジャーナルへの寄稿記事

Akamine, S, Ishizaki, Y, Sakai, Y, Torisu, H, Fukai, R, Miyake, N, Okubo, K, Koga, H, Sanefuji, M, Sakata, A, Kimura, M, Yamaguchi, S, Sakamoto, O, Hara, T, Saitsu, H, Matsumoto, N & Ohga, S 2018, 'A male case with CDKL5-associated encephalopathy manifesting transient methylmalonic acidemia', European Journal of Medical Genetics, 巻. 61, 番号 8, pp. 451-454. https://doi.org/10.1016/j.ejmg.2018.03.003
Akamine, Satoshi ; Ishizaki, Yoshito ; Sakai, Yasunari ; Torisu, Hiroyuki ; Fukai, Ryoko ; Miyake, Noriko ; Okubo, Kazuhiro ; Koga, Hiroshi ; Sanefuji, Masafumi ; Sakata, Ayumi ; Kimura, Masahiko ; Yamaguchi, Seiji ; Sakamoto, Osamu ; Hara, Toshiro ; Saitsu, Hirotomo ; Matsumoto, Naomichi ; Ohga, Shoichi. / A male case with CDKL5-associated encephalopathy manifesting transient methylmalonic acidemia. :: European Journal of Medical Genetics. 2018 ; 巻 61, 番号 8. pp. 451-454.
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AU - Fukai, Ryoko

AU - Miyake, Noriko

AU - Okubo, Kazuhiro

AU - Koga, Hiroshi

AU - Sanefuji, Masafumi

AU - Sakata, Ayumi

AU - Kimura, Masahiko

AU - Yamaguchi, Seiji

AU - Sakamoto, Osamu

AU - Hara, Toshiro

AU - Saitsu, Hirotomo

AU - Matsumoto, Naomichi

AU - Ohga, Shoichi

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N2 - Mutations in the X-linked gene CDKL5 cause early-onset epileptic encephalopathy and severe developmental delay. Because this disorder predominantly affects females, the full clinical spectrum of male patients remains elusive. We herein report a 16-year-old boy, who suffered from intractable seizures 20 days after birth. Serial electroencephalograms detected recurrent focal epileptiform discharges from age 4 months, which evolved to hypsarrhythmia later in infancy. Mass-spectrometric analyses revealed increase in urinary excretion of methylmalonic acid without perturbed concentrations of propionic acid, homocystein and methionine. Whole-exome sequencing identified a de novo, truncating mutation in CDKL5 (NM_003159.2:c.419dupA, p.Asn140Lysfs*8). Targeted sequencing excluded concomitant mutations in methylmalonic academia-associated genes. No methylmalonic acidemia has been reported in children with CDKL5 disorder. Extensive analyses on organic acid metabolism for males with CDKL5 mutations will gain more insight into their biochemical profiles in infancy.

AB - Mutations in the X-linked gene CDKL5 cause early-onset epileptic encephalopathy and severe developmental delay. Because this disorder predominantly affects females, the full clinical spectrum of male patients remains elusive. We herein report a 16-year-old boy, who suffered from intractable seizures 20 days after birth. Serial electroencephalograms detected recurrent focal epileptiform discharges from age 4 months, which evolved to hypsarrhythmia later in infancy. Mass-spectrometric analyses revealed increase in urinary excretion of methylmalonic acid without perturbed concentrations of propionic acid, homocystein and methionine. Whole-exome sequencing identified a de novo, truncating mutation in CDKL5 (NM_003159.2:c.419dupA, p.Asn140Lysfs*8). Targeted sequencing excluded concomitant mutations in methylmalonic academia-associated genes. No methylmalonic acidemia has been reported in children with CDKL5 disorder. Extensive analyses on organic acid metabolism for males with CDKL5 mutations will gain more insight into their biochemical profiles in infancy.

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