Homozygosity for disease-causing variants in AMT and GLDC in a patient with severe nonketotic hyperglycinemia

Andy Drackley, Merlene Peter, Pamela Rathbun, Alexander Ing, Carlos E. Prada, Kai Lee Yap*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Nonketotic hyperglycinemia (NKH) is a relatively well-characterized inborn error of metabolism that results in a combination of lethargy, hypotonia, seizures, developmental arrest, and, in severe cases, death early in life. Three genes encoding components of the glycine cleavage enzyme system—GLDC, AMT, and GCSH—are independently associated with NKH. We report on a patient with severe NKH in whom the homozygous pathogenic variant in AMT (NM_000481.3):c.602_603del (p.Lys201Thrfs*75) and the homozygous likely pathogenic variant in GLDC(NM_000170.2):c.2852C>A (p.Ser951Tyr) were both identified. Our patient demonstrates a novel combination of two homozygous disease-causing variants impacting the glycine cleavage pathway at two different components, and elicits management- and genetic counseling-related challenges for the family.

Original languageEnglish (US)
Article numbere63622
JournalAmerican Journal of Medical Genetics, Part A
Volume194
Issue number8
DOIs
StatePublished - Aug 2024

Keywords

  • AMT
  • GLDC
  • NKH
  • glycine encephalopathy
  • inborn error of metabolism
  • nonketotic hyperglycinemia

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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