Two novel missense mutations in nonketotic hyperglycinemia

Area of Science:

• Biochemistry
• Genetics
• Neurology

Background:

• Nonketotic hyperglycinemia (NKH) is an autosomal recessive metabolic disorder.
• It results from a deficiency in the mitochondrial glycine cleavage system.
• NKH leads to glycine encephalopathy, affecting brain function.

Observation:

• Two neonates presented with respiratory failure and myoclonic seizures.
• Elevated cerebrospinal fluid/plasma glycine ratios were observed.
• These clinical signs are indicative of nonketotic hyperglycinemia.

Findings:

• Two novel homozygous mutations were identified in the affected neonates.
• A missense mutation (c.593A>T, p.D198V) in the glycine decarboxylase (GLDC) gene was found.
• A splicing mutation (c.339G>A, Q113Q) in the aminomethyltransferase (AMNT) gene was detected.

Implications:

• These findings contribute to understanding the genetic heterogeneity of NKH.
• The identified mutations expand the known mutation spectrum for GLDC and AMNT.
• This research underscores the importance of regional genetic differences in inherited metabolic diseases.