RESUMEN
Objective:To study the phenotypes and genotypes of neonatal nonketotic hyperglycinemia (NKH).Methods:A neonate with severe NKH admitted to our hospital was retrospectively analyzed. Using keywords 'glycine cleavage enzyme', 'glycine decarboxylase', 'nonketotic hyperglycinemia' and 'glycine encephalopathy' (both in Chinese and English), multiple medical databases were searched until December 31, 2022. The clinical phenotypes and genotypes of neonatal NKH were summarized.Results:For our case, the neonate was lethargy and had no appetite on the second day of life, followed by recurrent seizures and irregular breathing, requiring mechanical ventilation. She died at 3 weeks of age. Two compound heterozygous variants were found in GLDC gene from whole exome sequencing , one was c.848C>G(p.A283G) of maternal origin and one was c.1607G>A(p.R536Q) of paternal origin. The former was a novel mutation. A total of 54 cases (including this case) were collected. The main clinical manifestations included poor feeding, decreased muscle tone, hiccups, progressive lethargy, irregular breathing, apnea and neonatal seizures. 42 cases (77.8%) had GLDC gene mutations, 9 cases (16.7%) had AMT gene mutations, 2 cases (3.7%) had LIAS gene mutations and 1 case (1.9%) had GCSH gene mutations. Conclusions:Neurological manifestations are most common in neonatal NKH with wide clinical variations. GLDC gene mutations are the predominant pathogenic mutations.
RESUMEN
La hiperglicinemia no cetósica es una encefalopatía por glicina autosómica recesiva y hereditaria sumamente rara, causada por una deficiencia en el sistema enzimatico de división de la glicina mitocondrial, que provoca síntomas clínicos graves. La hiperglicinemia no cetósica se caracteriza por fenotipos diversos y complejos, por ejemplo, hipotonía, convulsiones, deterioro cognitivo, retrasos del desarrollo y espasmos mioclónicos que podrían causar apnea e incluso la muerte. En este artículo, presentamos el caso de un niño de 1 año con convulsiones mioclónicas, hipotonía y coma, con aumento de la concentración de glicina en el plasma y el líquido cefalorraquídeo y con un índice de glicina en líquido cefalorraquídeo/plasma de 0,24. Existen dos mutaciones heterocigotas novedosas que confirman el diagnóstico de hiperglicinemia no cetósica. Una es una mutación de aminoácido, c.2516A>G (p.Y839C), y la otra es una mutación en los sitios de corte y empalme, c.2457+2T>A, en el gen GLDC.
Nonketotic hyperglycinemia is an extremely rare autosomal recessively inherited glycine encephalopathy caused by a deficiency in the mitochondrial glycine cleavage system, which leads to severe clinical symptoms. Nonketotic hyperglycinemia is characterized by complex and diverse phenotypes, such as hypotonia, seizures, cognitive impairment, developmental delays and myoclonic jerks that may lead to apnea and even death. Here we report a 1-year-old boy with myoclonic seizures, hypotonia and coma; he had elevated plasma and cerebrospinal fluid glycine levels, and cerebrospinal fluid/plasma glycine ratio was 0.24. Two novel heterozygous mutations confirm the diagnosis of nonketotic hyperglycinemia. One is a missense mutation c.2516A>G (p.Y839C) and the other one is a splicing mutation c.2457+2T>A in the GLDC gene.