TY - JOUR
T1 - Homozygosity for disease-causing variants in AMT and GLDC in a patient with severe nonketotic hyperglycinemia
AU - Drackley, Andy
AU - Peter, Merlene
AU - Rathbun, Pamela
AU - Ing, Alexander
AU - Prada, Carlos E.
AU - Yap, Kai Lee
N1 - Publisher Copyright:
© 2024 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.
PY - 2024/8
Y1 - 2024/8
N2 - 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.
AB - 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.
KW - AMT
KW - GLDC
KW - NKH
KW - glycine encephalopathy
KW - inborn error of metabolism
KW - nonketotic hyperglycinemia
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U2 - 10.1002/ajmg.a.63622
DO - 10.1002/ajmg.a.63622
M3 - Article
C2 - 38572626
AN - SCOPUS:85189983839
SN - 1552-4825
VL - 194
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
IS - 8
M1 - e63622
ER -