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AR = autosomal recessive; CSF = cerebrospinal fluid; DD = developmental delay; GCS = glycine cleavage enzyme system; IVA = isovaleric acidemia; MMA = methylmalonic aciduria; MOI = mode of inheritance; NKH = nonketotic hyperglycinemia; PA = propionic acidemia; PLPBP = pyridoxal 5'-phosphate-binding protein; PNPO = pyridoxamine 5'-phosphate oxidase; XL = X-linked

"Variant NKH" refers to glycine encephalopathy with elevated glycine levels and deficient GCS activity without GLDC or AMT pathogenic variants, most commonly due to deficiencies in the metabolism of GCS cofactors including lipoate deficiency and pyridoxal phosphate deficiency.

Impaired lipoylation or deficient lipoate due to biallelic pathogenic variants in genes encoding either lipoate synthesis (e.g., LIAS and LIPT2) or in the synthesis of the iron-sulfur cluster necessary for the function of lipoate synthase (e.g., BOLA3, GLRX5, IBA57, or NFU1) [Baker et al 2014].

Pyridoxal phosphate is a cofactor for the glycine cleavage enzyme system. Insufficient pyridoxal phosphate results in elevated glycine levels.

Clayton et al [2003], Mills et al [2005], Hoffmann et al [2007], Wilson et al [2019]

Scalais et al [2017]

"Ketotic hyperglycinemia" is a term used in the past to refer to genetic disorders in which GCS activity is secondarily inhibited in particular for several organic acidurias [Hayasaka & Tada 1983].