Progressive myoclonic epilepsy as an expanding phenotype of NGLY1-associated congenital deglycosylation disorder: A case report and review of the literature

Yuri Sonoda; Atsushi Fujita; Michiko Torio; Takahiko Mukaino; Ayumi Sakata; Masaru Matsukura; Kousuke Yonemoto; Ken Hatae; Yuko Ichimiya; Pin Fee Chong; Masayuki Ochiai; Yoshinao Wada; Machiko Kadoya; Nobuhiko Okamoto; Yoshiko Murakami; Tadashi Suzuki; Noriko Isobe; Hiroshi Shigeto; Naomichi Matsumoto; Yasunari Sakai; Shouichi Ohga

doi:10.1016/j.ejmg.2023.104895

Progressive myoclonic epilepsy as an expanding phenotype of NGLY1-associated congenital deglycosylation disorder: A case report and review of the literature

Eur J Med Genet. 2024 Feb:67:104895. doi: 10.1016/j.ejmg.2023.104895. Epub 2023 Dec 7.

Authors

Yuri Sonoda¹, Atsushi Fujita², Michiko Torio³, Takahiko Mukaino⁴, Ayumi Sakata⁵, Masaru Matsukura⁶, Kousuke Yonemoto⁶, Ken Hatae⁶, Yuko Ichimiya³, Pin Fee Chong³, Masayuki Ochiai¹, Yoshinao Wada⁷, Machiko Kadoya⁸, Nobuhiko Okamoto⁹, Yoshiko Murakami¹⁰, Tadashi Suzuki¹¹, Noriko Isobe⁴, Hiroshi Shigeto¹², Naomichi Matsumoto², Yasunari Sakai¹³, Shouichi Ohga³

Affiliations

¹ Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Research Center for Environment and Developmental Medical Sciences, Kyushu University, Fukuoka, Japan.
² Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.
³ Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
⁴ Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
⁵ Department of Clinical Chemistry and Laboratory Medicine, Kyushu University Hospital, Fukuoka, Japan.
⁶ Department of Pediatrics, Japanese Red Cross Fukuoka Hospital, Fukuoka, Japan.
⁷ Department of Obstetric Medicine, Osaka Women's and Children's Hospital, Osaka, Japan; Department of Molecular Medicine, Osaka Women's and Children's Hospital, Osaka, Japan.
⁸ Department of Molecular Medicine, Osaka Women's and Children's Hospital, Osaka, Japan.
⁹ Department of Molecular Medicine, Osaka Women's and Children's Hospital, Osaka, Japan; Department of Medical Genetics, Osaka Women's and Children's Hospital, Osaka, Japan.
¹⁰ Research Institute for Microbial Diseases and WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan.
¹¹ Glycometabolic Biochemistry Laboratory, RIKEN Cluster for Pioneering Research, Saitama, Japan; Takeda-CiRA Joint Program (T-CiRA), Kanagawa, Japan.
¹² Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Division of Medical Technology, Department of Health Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
¹³ Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: [email protected].

PMID: 38070824
DOI: 10.1016/j.ejmg.2023.104895

Abstract

Introduction: NGLY1-associated congenital disorder of deglycosylation (CDDG1: OMIM #615273) is a rare autosomal recessive disorder caused by a functional impairment of endoplasmic reticulum in degradation of glycoproteins. Neurocognitive dysfunctions have been documented in patients with CDDG1; however, deteriorating phenotypes of affected individuals remain elusive.

Case presentation: A Japanese boy with delayed psychomotor development showed ataxic movements from age 5 years and myoclonic seizures from age 12 years. Appetite loss, motor and cognitive decline became evident at age 12 years. Electrophysiological studies identified paroxysmal discharges on myoclonic seizure and a giant somatosensory evoked potential. Perampanel was effective for controlling myoclonic seizures. Exome sequencing revealed that the patient carried compound heterozygous variants in NGLY1, NM_018297.4: c.857G > A and c.-17_12del, which were inherited from mother and father, respectively. A literature review confirmed that myoclonic seizures were observed in 28.5% of patients with epilepsy. No other patients had progressive myoclonic epilepsy or cognitive decline in association with loss-of-function variations in NGLY1.

Conclusion: Our data provides evidence that a group of patients with CDDG1 manifest slowly progressive myoclonic epilepsy and cognitive decline during the long-term clinical course.

Keywords: Congenital disorder of deglycosylation (CDDG); Deterioration; NGLY1; Progressive myoclonic epilepsy (PME); Somatosensory evoked potential (SEP).

Publication types

Review
Case Reports

MeSH terms

Child
Child, Preschool
Congenital Disorders of Glycosylation*
Epilepsies, Myoclonic* / drug therapy
Epilepsies, Myoclonic* / genetics
Humans
Male
Mutation
Myoclonic Epilepsies, Progressive* / genetics
Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase / deficiency*
Phenotype
Seizures

Substances

Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase

Supplementary concepts

NGLY1 deficiency