Variant nonketotic hyperglycinemia caused by a novel pathogenic mutation in the glrx5 gene

Nonketotic hyperglycinemia (NKH) is caused by defects in the glycine cleavage system. Hyperglycinemia without biallelic mutations in one of the 4 genes that encode the constituents of the glycine cleavage system is classified as ‘variant NKH’. The defects in these cases are in the iron-sulphur cluster biogenesis and lipoate synthesis pathways. The GLRX5 gene is one of the genes in these new pathways. We report here an 8.5-year-old male patient presented with spasticity, ataxia and optic atrophy. He lost his ability to walk after a febrile infection at the age of 1.5 year. The patient’s cognitive functions were preserved. His plasma glycine level and cerebrospinal fluid/plasma glycine ratio were high. A novel homozygous mutation p.Gly116Asp (c.347G>A) in the GLRX5 gene was identified by whole exome sequencing. In conclusion, in a child, who have neurological regression, spasticity, ataxia, and whom cognitive functions are partially preserved, if plasma glycine level is high, variant NKH should be considered in the differential diagnosis.