A 15-Year-Old Boy in Long-Term Remission of Epileptic Seizures With Infantile-Onset Attenuated Nonketotic Hyperglycinemia

Nonketotic hyperglycinemia (NKH) is a rare autosomal recessive disorder caused by defects in the glycine cleavage system. Most patients with early-onset NKH present with severe manifestations, including poor neurological outcomes and refractory seizures. However, a proportion of neonatally presenting patients exhibit the attenuated phenotype, characterized by variable clinical features. We report a boy with infantile-onset NKH who achieved long-term seizure remission into adolescence. A three-month-old boy developed infantile spasms refractory to standard antiepileptic drugs and worsened by valproic acid. Laboratory findings revealed elevated glycine levels in plasma and cerebrospinal fluid with an increased CSF/plasma ratio of glycine. A glycine breath test indicated partial reduction of glycine metabolism. He was diagnosed with early-onset NKH at nine months, and thereafter, specific treatments were started with sodium benzoate and dextromethorphan. He exhibited severe developmental delay under sustained seizure control. Genetic testing at 11 years of age revealed compound heterozygous variants in the <i>AMT</i> gene: a novel missense variant (p.L116R) and a pathogenic frameshift variant (p.P20fs*76). At 15 years, he presented with tremor as rhythmic limb shaking and lethargy with abnormal 5 Hz waves in the electroencephalogram during influenza A, whereas any epileptic seizures did not occur. No suggestive findings of encephalitis were observed on brain MRI or CSF analysis, but steroid pulse therapy was administered along with baseline NKH therapy. No seizures occurred, and neurological findings seemed unaffected by this episode. This case illustrates that attenuated NKH can be well managed with sustained seizure-free status into adolescence, even in and after subclinical influenza encephalopathy, suggesting potential prophylactic effects of sodium benzoate and dextromethorphan.