Compliance to Clinical Guidelines Determines Outcome in Glutaric Aciduria Type I in the Era of Newborn Screening

Abstract

We report on a 4.5-year-old patient diagnosed with Glutaric aciduria type I (GAI), an autosomal recessive inborn error of lysine, hydroxylysine and tryptophan metabolism. Enzymatic assay in cultivated skin fibroblasts revealed complete absence of glutaryl-CoA dehydrogenase activity. All 11 Exons of the GCDH-Gen were sequenced and homozygosity for a yet undescribed mutation was identified. The patient was treated following the recently published guidelines for GA-I. Following this treatment regimen, the child developed normally without any manifest clinical crises. Our patient provides evidence that early commencement and strict adherence to treatment improves clinical outcome even in patients with complete absence of enzyme activity.

Zusammenfassung

Wir berichten über einen 4,5-jährigen Patienten mit Glutarazidurie Typ I (GA-I), einer autosomal-rezessiv vererbten Störung des Lysin-, Hydroxylysin- und Tryptophanstoffwechsels. Der Enzymassay in kultivierten Hautfibroblasten zeigte keine Aktivität der Glutaryl-CoA-Dehydrogenase (GCDH) bei Homozygotie für eine bisher nicht beschriebene Mutation. Wir behandelten den Patienten nach den derzeitigen Richtlinien für GA-I. Unter dieser Therapie entwickelte sich das Kind normal ohne metabolische Krisen. Dieser Bericht zeigt, dass bei konsequentem Einhalten der Therapie von Geburt an die Prognose auch bei Kindern mit einem völligen Fehlen der Enzymaktivität positiv beeinflusst werden kann.

Key words

glutaric aciduria type I - newborn screening - macrocephaly - glutaryl-CoA-dehydrogenase gene

Schlüsselwörter

Glutarazidurie Typ I - Neugeborenenscreening - Makrozephalie - Glutaryl-CoA-Dehydrogenase-Gen

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