Persistent NKH with transient or absent symptoms and a homozygous GLDC mutation

Abstract

Three of four nonketotic hyperglycinemia patients homozygous for a novel GLDC mutation (A802V) were treated by assisted respiration and/or sodium benzoate with or without ketamine and had transient neonatal or absent symptoms and normal developmental outcome, despite persisting biochemical evidence of nonketotic hyperglycinemia. This exceptional outcome may be related to the high residual activity of the mutant protein (32% of wild type) and therapeutic intervention during a critical period of heightened brain exposure and sensitivity to glycine.

A single nucleotide substitution that abolishes the initiator methionine codon of the GLDC gene is prevalent among patients with glycine encephalopathy in Jerusalem

“…Consanguinity in this population is common and has been estimated at $33% of all marriages (Jaber et al 2000). Interestingly, DNA analysis of another family from a different area near Jerusalem revealed another causative mutation (Korman et al 2004). Thus, based on the theoretical calculations presented previously (Zlotogora et al 1996), it may be surmised that the mutation reported here occurred around five generations ago.…”

The Calm before the Storm”: Late Onset Glycine Encephalopathy Masquerading as Gastro-oesophageal Reflux

“…In general, the presentation in the atypical neonatal form is similar to the classic neonatal form with hypotonia and apnoeic episodes but the outcome is significantly better [7] and rarely completely normal development has been reported [8].…”

“…Broadly based on the age of initial presentation they can be divided into 3 main types: Neonatal (0-4 weeks), Infantile (5 weeks to 2 years) and lateonset (beyond 2 years) [8].…”

“…Typically infants with this form have nearly normal development for the first 6 months of life and then present with mild to moderate developmental delay. Seizures, occurring in less than half of the patients, can be of any type (epileptic spasms, complex partial, tonic or generalised tonic-clonic) and are relatively easy to control [8].…”

“…Therapy is focused on managing seizures by using sodium benzoate to reduce the plasma concentration of glycine. NMDA receptor antagonists (ketamine, dextromethorphan, felbamate, and topiramate) are also used in this condition [8].…”