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

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

来源：European Journal of Medical Genetics, 2018, 61(8): 451-454.

DOI：10.1016/j.ejmg.2018.03.003

• Methylmalonic acidemia
• Whole-exome sequencing
• De novo mutation
• CDKL5
• Early-onset epileptic encephalopathy

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.

• 出版日期2018-8