Dos mutaciones novedosas en el gen de glicina descarboxilasa en un niño con hiperglicinemia no cetósica clásica: a propósito de un caso / Two novel mutations in the glycine decarboxylase gene in a boy with classic nonketotic hyperglycinemia: case report

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.

Using the fluorescence spot test for neonatal screening of G6PD deficiency.

To establish the neonatal screening method of glucose-6 phosphate dehydrogenase (G6PD) deficiency, G6PD activity was measured using the fluorescence spot test (FST) using dried blood samples on filter paper. The G6PD/6PGD rate test of venous blood samples was further performed for confirmation. The positive G6PD deficiency rate was 4.2% and its detection rates were 3.7% for all neonates and 5.2% only for male newborns when FST was used for neonatal screening. Conformation rates by use of G6PD/ 6PGD ratio test for G6PD deficiency were 86.8% and 100% particularly in the severely deficient groups. Both sensitivity and specificity were very high in the severely deficient groups. FST can be used in neonatal screening of G6PD deficiency because of its high accuracy, applicability, and simplicity. Moreover, a high volume of dried blood samples on filter paper can be tested quickly. It is very favorable to diagnose and treat G6PD deficiency early in high incidence districts.

A survey for the incidence of phenylketonuria in Guangdong, China.

A multicenter cooperative investigated the incidence of Phenylketonuria (PKU) in the central, southern and western areas of Guangdong province and its surrounding districts. Tests to measure phenylalanine (Phe) on dried blood spots on filter paper cards used BIA and thefluorescence assay. Four hundred sixty-one thousand eight hundred five (461,805) newborns were screened and 14 cases of persistent hyperphenylalaninemia (PHPA) were detected. The incidence of PHPA was 1/33,000, including 1/77,000 for classical PKU; 1 in 66,000 for hyperphenylalaninemia (HPA) and 1 in 461,805 for BH4 deficiency. A high variation in PKU incidence in the different districts was observed. The differences may be attributed to the variations in gene frequency of PKU in the different districts and to bioethical consideration especially as regards reproduction in different areas.